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Protein phosphorylation, controlled by protein kinases, is central to regulating various pathophysiological processes, including cardiac systolic function. The dysregulation of protein kinase activity plays a significant role in the pathogenesis of cardiac systolic dysfunction. While cardiac contraction mechanisms are well documented, the mechanisms underlying cardiac diastole remain elusive. This gap persists owing to the historical focus on systolic dysfunction in heart failure research. Recently, heart failure with preserved ejection fraction (HFpEF), an age-related disease characterized by cardiac diastolic dysfunction, has emerged as a major public health concern. However, its underlying mechanism remains unclear. In this study, we investigated cardiac protein kinases by analyzing the gene expression of 518 protein kinases in human tissues. We identified alpha-kinase 2 (ALPK2) as a novel cardiac-specific atypical kinase and generated tamoxifen-inducible, cardiomyocyte-specific Alpk2-knockout mice and Alpk2-overexpressing mice. Alpk2 deficiency did not affect cardiac systolic dysfunction in the myocardial infarction model or the pressure-overload-induced heart failure model. Notably, cardiomyocyte-specific Alpk2 deficiency exacerbated cardiac diastolic dysfunction induced by aging and in the HFpEF model. Conversely, Alpk2 overexpression increased the phosphorylation of tropomyosin 1, a major regulator that binds myosin to actin, and mitigated cardiac stiffness in HFpEF. This study provides novel evidence that ALPK2 represents a potential therapeutic target for cardiac diastolic dysfunction in HFpEF and age-related cardiac impairments., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Upon entering the environment, Microplastics (MPs) experience aging processes that modify their properties and integrity. Previous methods for predicting the incipient motion of MPs have been validated using pristine plastics, which do not account for the effects of aging. This can lead to uncertainties in both quantification and characterization. This study investigates the effect of aging on the incipient motion of MPs with different bed roughness (smooth and rough beds) and MP properties (e.g., grain sizes and densities) in an open-channel flow. Five types of MPs were subjected to four different degrees of aging using the Fenton reagent, and their incipient velocities were tested on beds with two distinct roughness. The results suggest that the incipient velocity of MPs increases linearly with aging. However, this increase is not uniform across different particles and bed roughness. Upon comparing various commonly employed sediment incipient velocity equations, experimental results are in agreement with Ruijin Zhang's equation as the most precise. The parameters in Ruijin Zhang's equation are modified to enhance its applicability for predicting the incipient velocity of aged MPs. This study provides novel insights into the incipient motion of aged MPs in an open-channel flow, highlighting the intricate interaction between aged MP characteristics and bed roughness., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Commensal bacteria and their derivatives hold significant promise as therapeutic interventions to delay aging. However, with the diverse nature of the soil microbiome and the long lifespan of mammalian models, the exploration of the influence of soil bacteria and bacteria-derived molecules on host aging remains limited. We conducted a lifespan screening in Caenorhabditis elegans using plant root bacterial collection. Our screening identified 8 genera of bacterial isolates capable of extending lifespan, with Mycobacterium sp. Root265 exhibits the most pronounced effect on lifespan extension. Biochemical analysis revealed two specific molecules derived from Root265, polysaccharides (PSs) and arabinogalactan peptidoglycan (AGP), responsible for lifespan extension via daf-16-dependent and -independent pathways, respectively. Notably, AGP exhibited a unique ability to enhance protein homeostasis effectively. Moreover, polar lipids originating from Root265 were found to extend lifespan while mitigating age-related BAS-1 decline in neurons. Intriguingly, even brief exposures to these bioactive compounds were sufficient to achieve the lifespan-promoting effects. We found diverse beneficial bacteria and anti-aging active compounds from soil bacteria. These findings highlight the potential of exploring bacterial derivatives as therapies targeting aging without the constraints associated with direct microbial interventions., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Introduction: Neighborhood environments may promote neurocognitive health in part by providing amenities that encourage physical activity. We examined associations between quantity of walkable facilities, including specifically physical activity facilities (e.g., gyms, recreation centers), with risk of incident dementia., Methods: Participants included 2923 adults ≥ 65 years old from the Cardiovascular Health Cognition Study (1992-1999), with clinically adjudicated dementia classified over a median 6.0 years of follow-up. Walkable facilities were measured within 1 km (Euclidean) of home. Self-reported baseline physical activity was considered a moderator., Results: In adjusted Cox models, participants with ≥ 2 (vs. 0) physical activity facilities had reduced risk of mixed/vascular dementia, but not Alzheimer's disease, particularly after excluding individuals in the bottom 20th percentile of physical activity (hazard ratio = 0.56, 95% confidence interval: 0.35-0.89)., Discussion: Neighborhood amenities that encourage physical activity may mitigate dementia risk via improved vascular health, especially for individuals with sufficient baseline mobility to use these resources., Highlights: We examined associations between nearby walkable facilities and incident dementia. Facilities within 1 km were counted via the National Establishment Time Series Database. More physical activity facilities predicted lower risk of mixed/vascular dementia. No associations were found between walkable facilities and incident Alzheimer's disease., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Hematopoietic stem progenitor cells (HSPCs) give rise to the hematopoietic system, maintain hematopoiesis throughout the lifespan, and undergo molecular and functional changes during their development and aging. The importance of hematopoietic stem cell (HSC) biology has led to their extensive characterization at genomic and transcriptomic levels. However, the proteomics of HSPCs throughout the murine lifetime still needs to be fully completed. Here, using mass spectrometry (MS)-based quantitative proteomics, we report on the dynamic changes in the proteome of HSPCs from four developmental stages in the fetal liver (FL) and the bone marrow (BM), including E14.5, young (2 months), middle-aged (8 months), and aging (18 months) stages. Proteomics unveils highly dynamic protein kinetics during the development and aging of HSPCs. Our data identify stage-specific developmental features of HSPCs, which can be linked to their functional maturation and senescence. Our proteomic data demonstrated that FL HSPCs depend on aerobic respiration to meet their proliferation and oxygen supply demand, while adult HSPCs prefer glycolysis to preserve the HSC pool. By functional assays, we validated the decreased mitochondrial metabolism, glucose uptake, reactive oxygen species (ROS) production, protein synthesis rate, and increased glutathione S-transferase (GST) activity during HSPC development from fetal to adult. Distinct metabolism pathways and immune-related pathways enriched in different HSPC developmental stages were revealed at the protein level. Our study will have broader implications for understanding the mechanism of stem cell maintenance and fate determination and reversing the HSC aging process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Exercise preserves neuromuscular function in aging through unknown mechanisms. Skeletal muscle fibroblasts (FIB) and stem cells (MuSC) are abundant in skeletal muscle and reside close to neuromuscular junctions, but their relative roles in motor neuron maintenance remain undescribed. Using direct cocultures of embryonic rat motor neurons with either human MuSC or FIB, RNA sequencing revealed profound differential regulation of the motor neuron transcriptome, with FIB generally favoring neuron growth and cell migration and MuSC favoring production of ribosomes and translational machinery. Conditioned medium from FIB was superior to MuSC in preserving motor neurons and increasing their maturity. Lastly, we established the importance of donor age and exercise status and found an age-related distortion of motor neuron and muscle cell interaction that was fully mitigated by lifelong physical activity. In conclusion, we show that human muscle FIB and MuSC synergistically stimulate the growth and viability of motor neurons, which is further amplified by regular exercise., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Therapies involving the use of stem Leydig cells (SLCs), as testicular mesenchymal stromal cells, have shown great promise in the treatment of Leydig cell (LC) dysfunction in aging males. However, the outcomes of these therapies are not satisfactory. In this study, it is demonstrated that the aging microenvironment of the testicular interstitium impairs the function of SLCs, leading to poor regeneration of LCs and, consequently, inefficient functional restoration. The study develops a decellularized testicular extracellular matrix (dTECM) hydrogel from young pigs and evaluates its safety and feasibility as a supportive niche for the expansion and differentiation of SLCs. dTECM hydrogel facilitates the steroidogenic differentiation of SLCs into LCs, the primary producers of testosterone. The combination of SLCs with a dTECM hydrogel leads to a significant and sustained increase in testosterone levels, which promotes the restoration of spermatogenesis and fertility in an LC-deficient and aged mouse model. Mechanistically, collagen 1 within the dTECM is identified as a key factor contributing to these effects. Notably, symptoms associated with testosterone deficiency syndrome are significantly alleviated in aged mice. These findings may aid the design of therapeutic interventions for patients with testosterone deficiency in the clinic., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Introduction: Life satisfaction is a key indicator of successful ageing and reflects well-being. There is evidence of the association between life satisfaction and health behaviours among older adults. Therefore, this systematic review and meta-analysis protocol seeks to determine the strength and direction of the association between life satisfaction and health behaviours among older adults., Methods and Analysis: This protocol followed the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will search the electronic databases (MEDLINE, APA PsycINFO, Web of Science, CINAHL and Global Health) from inception to date. Only observational studies that described the association between life satisfaction and health behaviours-smoking, alcohol drinking, physical activity, diet/nutrition and sleep-will be included. Two independent reviewers will conduct screening, data extraction and risk of bias assessment of the articles. The risk of bias will be assessed using the Joanna Briggs Institute critical appraisal tools for cohort and analytical cross-sectional studies. Studies will be included in the meta-analysis if they report zero-order associations between life satisfaction and health behaviours; otherwise, a narrative synthesis will be presented., Ethics and Dissemination: This study does not require ethics approval, as it involves analysing secondary data from published studies. The completed review will be published in a peer-reviewed journal and presented at conferences., Trial Registration Number: PROSPERO (CRD42023441386)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The available literature reviews of shift work among care workers are almost exclusively focused on 8-hour shifts and 12-hour shifts or 24-hour on-call shifts for physicians. We do not yet know the scope of evidence regarding extended-duration work shifts (defined as on-duty shifts of 16 or more hours per shift) in diverse healthcare settings, such as the impact on care workers and recipients of care. In this proposed scoping review, we aim to provide an overview of the current research regarding extended-duration work shifts among care workers in various healthcare settings., Methods and Analysis: We will conduct this scoping review in accordance with the Joanna Briggs Institute scoping review methodology. Comprehensive searches will be conducted in PubMed, Embase, MEDLINE, Web of Science and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases and grey literature sources. We will include empirical studies that focus on extended-duration work shifts among care workers working in different healthcare settings, including home care, community, acute care settings, long-term care homes and assisted living facilities. We will not apply language restrictions. We will conduct searches in August 2024, followed by screening of records. We will exclude research on on-call work shifts and investigations that solely focus on interns. The included literature will be screened independently by pairs of reviewers at the title and abstract review phase, followed by a full-text review for relevant literature. Any disagreement will be resolved by consensus or discussion with a third reviewer. The results will be extracted and summarised in the final report in tabular form, when possible, along with narrative synthesis., Ethics and Dissemination: All data for this study will come from published literature, so an ethics review is not necessary. The findings will be disseminated through conference presentations and publication in peer-reviewed journals, with the expectation that they will guide future research and inform future management of work shifts in care workers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Human induced pluripotent stem cells represent a scalable source of youthful tissue progenitors and secretomes for regenerative therapies. The aim of our study was to investigate the potential of conditioned medium (CM) from hiPSC-mesenchymal progenitors (hiPSC-MPs) to stimulate osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (MSCs). We also investigated whether prolonged cultivation or osteogenic pre-differentiation of hiPSC-MPs could enhance the stimulatory activity of CM., Methods: MSCs were isolated from 13 donors (age 20-90 years). CM derived from hiPSC-MPs was added to the MSC cultures and the effects on proliferation and osteogenic differentiation were examined after 14 days and 6 weeks. The stimulatory activity of hiPSC-MP-CM was compared with the activity of MSC-derived CM and with the activity of CM prepared from hiPSC-MPs pre-cultured in growth or osteogenic medium for 14 days. Comparative proteomic analysis of CM was performed to gain insight into the molecular components responsible for the stimulatory activity., Results: Primary bone marrow-derived MSC exhibited variability, with a tendency towards lower proliferation and tri-lineage differentiation in older donors. hiPSC-MP-CM increased the proliferation and alkaline phosphatase activity of MSC from several adult/aged donors after 14 days of continuous supplementation under osteogenic conditions. However, CM supplementation failed to improve the mineralization of MSC pellets after 6 weeks under osteogenic conditions. hiPSC-MP-CM showed greater enhancement of proliferation and ALP activity than CM derived from bone marrow-derived MSCs. Moreover, 14-day cultivation but not osteogenic pre-differentiation of hiPSC-MPs strongly enhanced CM stimulatory activity. Quantitative proteomic analysis of d14-CM revealed a distinct profile of components that formed a highly interconnected associations network with two clusters, one functionally associated with binding and organization of actin/cytoskeletal components and the other with structural constituents of the extracellular matrix, collagen, and growth factor binding. Several hub proteins were identified that were reported to have functions in cell-extracellular matrix interaction, osteogenic differentiation and development., Conclusions: Our data show that hiPSC-MP-CM enhances early osteogenic differentiation of human bone marrow-derived MSCs and that prolonged cultivation of hiPSC-MPs enhances CM-stimulatory activity. Proteomic analysis of the upregulated protein components provides the basis for further optimization of hiPSC-MP-CM for bone regenerative therapies., Competing Interests: Declarations Ethics approval and consent to participate The study was conducted with informed consent for the research use of tissue remaining after surgery and with full ethical approval by the Ethics Committee for the AUVA Hospitals (“Ethikkomission der AUVA”, Vienna, Austria)”, approval No. 1/2005, title “Tracking and improving cartilage regeneration in a human cartilage defect in vivo model” (“Vervolgung und Verbesserung der Knorpelregeneration in einem humanen Knorpeldefekt in vivo Modell”), approved February 9th 2006, and amendment from September 28th 2009, to include “The extraction of demineralized bone, analytical determinations in the spongiosa area, and isolation of osteoblasts and bone marrow” (“Die Gewinnung von demineralisiertem Knochen, Analytische Bestimmungen im Spongiosabereich, isolierung von Osteoblasten und Knochenmark”). The patients provided written informed consent for the use of samples. Consent for publication All authors confirm their consent for publication. Competing interests Authors of the study declare no competing interests., (© 2024. The Author(s).)

Advanced age increases the risk of severe disease from SARS-CoV-2 infection, as well as incidence of long COVID and SARS-CoV-2 reinfection. We hypothesized that perturbations in the aged antiviral CD8 + T cell response predisposes elderly individuals to severe coronavirus infection, re-infection, and postinfectious cognitive sequelae. Using MHV-A59 as a murine model of respiratory coronavirus, we found that aging increased CNS infection and lethality to MHV infection. This was coupled with increased CD8 + T cells within the aged CNS but reduced antigen specificity. Aged animals also displayed a decreased proportion of CD103 + resident memory cells (T RM ), which correlated with increased severity of secondary viral challenge. Using a reciprocal adoptive transfer paradigm, data show that not only were fewer aged CD8 + T cells retained within the adult brain post-infection, but also that adult CD8 + cells expressed lower levels of T RM marker CD103 when in the aged microenvironment. Furthermore, aged animals demonstrated spatial learning impairment following MHV infection, which worsened in both aged and adult animals following secondary viral challenge. Spatial learning impairment was accompanied by increased TUNEL positivity in hippocampal neurons, suggestive of neuronal apoptosis. Additionally, primary cell coculture showed that activated CD8 + T cells induced TUNEL positivity in neurons, independent of antigen-specificity. Altogether, these results show that non-antigen specific CD8 + T cells are recruited to the aged brain and cause broad neuronal death without establishing a T RM phenotype that confers lasting protection against a secondary infection., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Homeostasis of proteins (proteostasis), which governs protein processing, folding, quality control, and degradation, is a fundamental cellular process that plays a pivotal role in various neurodegenerative diseases and in the natural aging process of the mammalian brain. While the role of neuronal proteostasis in neuronal physiology is well characterized, the contribution of proteostasis of glial cells, particularly of astrocytes, has received fairly less attention in this context. Here, we summarize recent data highlighting proteostasis dysfunction in astrocytes and its putative implication to neurodegenerative diseases and aging. We discuss how distinct proteostasis nodes and pathways in astrocytes may specifically contribute to brain function and different age-associated pathologies. Finally, we argue that the understanding of astrocytic proteostasis role in neuronal physiology and functional decay may arise as a potential new avenue of intervention in neurodegenerative diseases and grant relevant data in the biology of aging., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest with respect to the content of the manuscript, authorship, and/or publication of this article. CONFLICT OF INTEREST STATEMENT The author(s) declare no conflicts of interest with respect to the content of the manuscript, authorship, and/or publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims/hypothesis: Triglyceride (TG) /High density lipoprotein cholesterol (HDL-C) ratio (THR) is a surrogate predictor of hyperinsulinemia. To identify novel genetic loci for THR change over time (ΔTHR), we conducted genome-wide association study (GWAS) and genome-wide linkage scan (GWLS) among non-diabetic Europeans from the Long Life Family Study (LLFS, n=1384)., Methods: Subjects with diabetes or on dyslipidemia medications were excluded. ΔTHR was derived using growth curve modeling, and adjusted for age, sex, field centers, and principal components (PCs). GWAS used a linear mixed model accounting for familial relatedness. GWLS employed haplotype-based IBD estimation with 0.5 cM average spacing., Results: Heritability of ΔTHR was moderate (46%). Our GWAS identified a significant locus at the LPL (p=1.58e-9) for ΔTHR; this locus has been reported before influencing baseline THR levels. Our GWLS found significant linkage with a logarithm of the odds (LODs) exceeding 3 on 3q28 (LODs=4.1). Using a subset of 25 linkage enriched families, we assessed sequence elements under 3q28 and identified two novel variants (EIF4A2/ADIPOQ-rs114108468, p=5e-6, MAF=1.8%; TPRG1-rs16864075, p=3e-6, MAF=8%; accounted for ∼28% and ∼29% of the linkage, respectively). While the former variant was associated with EIF4A2 (p=7e-5) / ADIPOQ (p=3.49e-2) transcriptional levels, the latter variant was not associated with TPRG1 (p=0.23) transcriptional levels. Replication in the Framingham Heart Study Offspring Cohort (FOS) observed modest effect of these loci on ΔTHR., Conclusions: Our approach discovered two novel gene variants EIF4A2/ADIPOQ-rs114108468 and TPRG1-rs16864075 on 3q28 for ΔTHR among subjects without diabetes. Our findings provided novel insights into the molecular regulation of insulin resistance., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The conception of coffee consumption has undergone a profound modification, evolving from a noxious habit into a safe lifestyle actually preserving human health. The last 20 years also provided strikingly consistent epidemiological evidence showing that the regular consumption of moderate doses of coffee attenuates all-cause mortality, an effect observed in over 50 studies in different geographic regions and different ethnicities. Coffee intake attenuates the major causes of mortality, dampening cardiovascular-, cerebrovascular-, cancer- and respiratory diseases-associated mortality, as well as some of the major causes of functional deterioration in the elderly such as loss of memory, depression and frailty. The amplitude of the benefit seems discrete (17% reduction) but nonetheless corresponds to an average increase healthspan of 1.8 years of lifetime. This review explores evidence from studies in humans and human tissues supporting an ability of coffee and of its main components (caffeine and chlorogenic acids) to preserve the main biological mechanisms responsible for the aging process, namely genomic instability, macromolecular damage, metabolic and proteostatic impairments with particularly robust effects on the control of stress adaptation and inflammation and unclear effects on stem cells and regeneration. Further studies are required to detail these mechanistic benefits in aged individuals, which may prompt new insights into understanding of the biology of aging and the development of new senostatic strategies. Additionally, the safety of this lifestyle factor in the elderly prompts a renewed attention to recommending the maintenance of coffee consumption throughout life as a healthy lifestyle and to further exploring who gets the greater benefit with what schedules of which particular types and doses of coffee., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rodrigo A. Cunha reports was provided by University of Coimbra. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Declaration of interest The authors declare no conflict of interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cellular senescence is an irreversible cell cycle arrest induced by stresses such as telomere shortening and oncogene activation. It acts as a tumor suppressor mechanism that prevents the proliferation of potentially tumorigenic cells. Paradoxically, senescent stromal cells that arise in the tumor microenvironment have been shown to promote tumor progression. In addition, senescent cells that accumulate in vivo over time are thought to contribute to aging and age-related diseases. These deleterious effects of senescent cells involve the secretion of bioactive molecules such as inflammatory cytokines and chemokines, a phenomenon known as the senescence-associated secretory phenotype (SASP). While the role of cellular senescence in vivo is becoming increasingly clear, the intracellular signaling pathways that induce the expression of senescent phenotypes are not fully understood. In this review, we outline senescence-associated signaling pathways and their relevance to cancer and aging., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Japanese Biochemical Society.)

Sexuality is a fundamental part of human existence and it encompasses thoughts, desires, behaviors, relationships, as well as neuropsychological and physiological components. However, sexuality in older adults is under-researched from the neuropsychological and psychophysiological perspectives and is often neglected by healthcare providers in the clinical practice. This article aims to explore the state of the art on the neuropsychology and psychophysiology of older adults' sexuality, proposing future research directions and emphasizing its significance. By summarizing current knowledge on the sexuality of younger individuals, it was possible to lay the groundwork for formulating research questions about older adults' sexuality. The implications proposed in this article will potentially impact both the scientific and also the clinical field. In fact, gaining insights on the neuropsychological and psychophysiological aspects of sexuality in healthy older adults can also shed light into those with neurocognitive disorders., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Multidomain lifestyle interventions may have the potential to slow biological aging as captured by deficit accumulation frailty indices. We describe the distribution and composition of the 49-component frailty index (FI) developed by the U.S. POINTER clinical trial team of investigators and assess its cross-sectional associations with sociodemographic factors and markers chosen to be representative of behaviors targeted by the trial's multidomain interventions., Methods: We draw baseline data from the 2111 volunteers enrolled in U.S. POINTER who were ages 60-79 years and at increased risk for cognitive decline. Frailty components were grouped into nine domains. Associations that FI scores and their domains had with behavioral markers were described with correlations and canonical correlation., Results: The 25th, 50th, and 75th percentiles of the frailty index score distribution were 0.153, 0.189, and 0.235. Higher frailty scores tended to occur among individuals who were older, male, and living in areas of greater deprivation (all p<0.001). They were also associated with poorer self-reported diet, less physical activity, and higher Framingham risk scores (all p<0.001). Associations were diffusely distributed among the frailty component domains, indicating that no individual domain was dominating associations., Conclusions: The U.S. POINTER deficit accumulation frailty index had expected relationships with sociodemographic factors and sensitivity to the behaviors targeted by the trial's interventions. Our analysis supports its use as a secondary outcome to assess whether the multidomain interventions differentially impact an established marker of biological aging., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Magnetic seeded filtration (MSF) is a solid-liquid separation process based on the formation of hetero-agglomerates between target (non-magnetic) particles and added magnetic particles, followed by magnetic separation. Previous experimental studies reported high separation efficiencies for hydrophobic microplastic particles (MP) and focused mainly on the polymer type. This study investigates the influence of the particle size, morphology and aging on the separation efficiency of different polymer types. Surface morphology and particle size only marginally affect the separation of particles larger than 30μm. However, the agglomeration of particles in the lower micron range is increasingly dominated by repulsive electrostatic interactions. After oxidative treatment with Fenton's reagent, separation efficiencies for most MP remain between 55% and 96%. Exposure to UV light results in a significant decrease in separation efficiency, particularly for polystyrene, where the separation efficiency decreases from 86% to 9%. Mechanical aging, simulated by mixing MP in a sand matrix on a horizontal shaker, reduces the separation to below 50% for all polymer types. Exposure to UV light causes surface oxidation, as evidenced by the formation of carbonyl peaks in the Fourier transformed infrared spectra. Mechanical treatment results in the deposition of small silica particles on the MP surface, as revealed by electron microscopy. Both mechanisms render the polymer surface more hydrophilic and reduce the tendency to form hetero-agglomerates with (hydrophobic) magnetic seed particles. MSF is a promising technique for MP separation but also offers the possibility to probe surface properties of (environmentally aged) MPs. This study demonstrates that environmental aging can significantly affect the behavior of MP and highlights the importance of environmental aging in MP fate studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Muscle fatigue, the transient decrease in muscle power, leads to low levels of physical activity and an inability to perform activities of daily living. Altered muscle coordination in response to fatigue may contribute to impaired physical performance. We sought to determine whether lower extremity muscle coordination during gait changes differently depending on susceptibility to fatigue (i.e., fatigability). Thirty-one older adults completed muscle power testing before and after a 30-min walk, with the change in power used to categorize participants as more or less fatigable. We used non-negative matrix factorization to identify muscle modules from electromyography (EMG) from the 2nd minute as our measure of baseline muscle coordination. Changes in muscle coordination were determined by computing the variance in the 30th minute's EMG accounted for by the baseline modules across all muscles (tVAF) and in individual muscles (mVAF). We compared tVAF between the 2nd and 30th minutes of the walk in individuals who were more and less fatigable. We used mVAF to explore the contribution of changes in individual muscle activity to tVAF. There was a decrease in tVAF overall in response to the walk (p < 0.001; 92.3 ± 1.6 % vs. 89.0 ± 4.3 %) but this did not differ between groups (interaction p = 0.66). There were significant associations between mVAF and tVAF for knee extensor, knee flexor, and ankle dorsiflexor muscles. Our results suggest that muscle coordination changes over the course of a walk in older adults but that this change does not differ between more and less fatigable older adults., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Frailty is a heterogeneous syndrome with distinct patterns. This study aimed to identify frailty risk patterns and their predictive value for mortality in older adults., Design: Prospective longitudinal study., Setting and Participants: Data were obtained from a 2017 survey of 609 independently mobile adults aged 65 years and older in suburban Japan, focusing on those at risk for at least 1 frailty dimension., Methods: Frailty assessments were extracted from the Kihon checklist, and subgroups were identified using latent class analysis. Associations between frailty patterns and 3-year mortality were assessed using Kaplan-Meier survival analysis and Cox proportional hazards modeling., Results: Three frailty patterns were identified: "high risk of cognitive impairment" (76.0%), "moderate risk of cognitive, physical, and oral dysfunction" (14.3%), and "high risk of cognitive, physical, and functional decline" (9.7%). We recorded 52 deaths during a mean follow-up time of 25.7 months (standard deviation: 12.6) and a median follow-up time of 26.5 months. Kaplan-Meier analysis showed significant survival differences among the groups (log-rank: P < .001). Compared with the high risk of cognitive impairment group, the moderate risk of cognitive, physical, and oral dysfunction group had a 145% higher mortality risk (adjusted hazard ratio, 2.45; 95% confidence interval, 1.22-4.90), while the high risk of cognitive, physical, and functional decline group exhibited a 220% higher risk of mortality (adjusted hazard ratio, 3.20; 95% confidence interval, 1.53-6.70)., Conclusions and Implications: The findings reveal the heterogeneity of frailty among community-dwelling Japanese older adults, with a high prevalence of cognitive impairment risk. The subgroup with risk of cognitive, physical, and functional decline had the highest mortality risk, highlighting the need for multidimensional assessment and intervention., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

With one in every four older adults living with T2D and one in every two older adults meeting the criteria for prediabetes, neuromuscular changes due to T2D are likely to impact functional activities in this population. Limited work in evaluating motor unit number and size across muscles in the upper extremity in persons with Type II Diabetes (T2D) exists, mostly due to the traditional belief bias that the upper extremity is relatively spared in T2D as compared to the lower extremities. The purpose of the current study was to evaluate motor unit number and size (using electrophysiological motor unit number index (MUNIX) and motor unit size index (MUSIX)) across the upper extremity in older adults with T2D (n = 13) as compared to healthy age- and sex-matched controls (n = 12). Persons with T2D presented with more motor units and larger motor unit sizes (p < 0.05) as compared to age- and sex-matched control participants. These changes were not dependent upon muscle location within a limb, indicating systemic neuromuscular changes associated with T2D. These group effects were clarified when health state covariates (e.g., blood pressure) were accounted for. Findings are consistent with emerging data that show altered neuromuscular characteristics with health state considerations in persons with T2D., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Researchers and policymakers have used a four-pillar framework- condition, consistency, context, and cost-to describe the characteristics of housing that are important for health equity. We propose adding a fifth pillar: care and connection. Housing for care and connection refers to the housing design, institutional policies, and housing programs that strengthen social connections, caregiving relationships, access to resources, and a sense of self in community. Attending to these needs in housing is especially important for people who are in transition in and out of homelessness, living in poverty, are very young or very old, or living with a disability or activity limitation., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

The current experimental investigation reports the performance of intra-hybrid woven jute-sisal lignocellulosic fibers, and their polypropylene composites subjected to different aging conditions (distilled water, vegetable oil, and alkali solution) for a prolonged time of 6 months. The effect of different aging mediums on chemical composition of fibers, such as, variation in cellulose and hemicellulose content was analyzed to understand the degradation mechanisms and their structure property relationship established. Significant degradation in mechanical properties was observed with exposure to alkali followed by water mediums due to degradation of fibers and thereby results in poor interfacial characteristics, while sustained durability in terms of mechanical properties was observed with oil-based aging. Highest reduction was observed in tensile strength (11 % and 34 %), flexural strength (16 % and 20 %), tensile modulus (44 % and 58 %), and flexural modulus (51 % and 52 %) after 3-month and 6 months of alkali-aging, respectively as compared to un-aged specimens. Furthermore, the visual appeal of materials was significantly affected due to aging in an alkali solution followed by distilled water, while vegetable oil has not shown any visual degradation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

High sexual quality and activity predict psychological well-being in heterosexual middle-aged and older adults; however, these associations have not been documented in sexual minorities, who have faced lifelong stigma concerning their sexuality. This paper presents data from two secondary studies that explored the benefits of being sexually active and satisfied and the role of internalized homonegativity in a sample of middle-aged and older sexual minorities. Study 1 was a cross-sectional survey collected on 91 sexually active sexual minorities (ages 40-80) in same-sex relationships. Study 2 was a cross-sectional survey collected on 235 single and partnered sexual minorities (ages 40-90), which included sexually active (N = 101) and inactive (N = 134) participants. In Study 1, sexual satisfaction was associated with higher psychological well-being and dissatisfaction was more prominently associated with lower psychological well-being. In Study 2, we found that the sexually active participants had higher levels of psychological well-being, in addition to corroborating the Study 1 findings. Additionally, we also determined that sexual dissatisfaction was a mediator between internalized homonegativity and psychological well-being. These findings accentuate the benefits of retaining high sexual quality and activity for middle-aged and older sexual minorities. Although there are apparent advantages of being sexually satisfied, the relationship to psychological well-being is stronger and more of a concern for those who are dissatisfied, which is rooted in internalized homonegativity. These results can guide practitioners working with middle-aged and older sexual minorities to help them achieve successful aging trajectories by reducing their internalized homonegativity and promoting higher sexual quality., Competing Interests: Declarations Conflict of interest The authors have no competing interests to declare that are relevant to the content of this article. Both authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. Ethics Approval The methodology and materials presented in both studies (Study 1 IRB# 20171106 and Study 2 IRB# 20201102) were approved by the University of Akron Institutional Review Board. Informed consent Informed consent was obtained from all individuals across both studies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ageing is an inevitable and multifaceted biological process that impacts a wide range of cellular and molecular mechanisms, leading to the development of various diseases, such as liver fibrosis. Liver fibrosis progresses to cirrhosis, which is an advanced form due to high amounts of extracellular matrix and restoration of normal liver structure with failure to repair damaged tissue and cells, marking the end of liver function and total liver failure, ultimately death. The most important factors are reactive oxygen species (ROS) and cellular senescence. Oxidative stress is defined as an impairment by ROS, which are by-products of the mitochondrial electron transport chain and other key molecular pathways that induce cell damage and can activate cellular senescence pathways. Cellular senescence is characterized by pro-inflammatory cytokines, growth factors, and proteases secreted by senescent cells, collectively known as the senescence-associated secretory phenotype (SASP). The presence of senescent cells, which disrupt tissue architecture and function and increase senescent cell production in liver tissues, contributes to fibrogenesis. Hepatic stellate cells (HSCs) are activated in response to chronic liver injury, oxidative stress, and senescence signals that drive excessive production and deposition of extracellular matrix. This review article aims to provide a comprehensive overview of the pathogenic role of ROS and cellular senescence in the aging liver and their contribution to fibrosis., Competing Interests: Declarations Competing interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Diabetes is one of the most pressing health issues in the Southeast Asian region, and hypertension has been commonly reported as a comorbidity in adults with diabetes. This systematic review aimed to synthesize evidence on the prevalence and management of hypertension in adults with diabetes in Southeast Asian countries. A literature search was conducted in Ovid MEDLINE and Embase Classic + Embase from database inception until March 15, 2024. Studies were included if (1) they were conducted in Southeast Asian countries, (2) the study populations were adults with diabetes, and (3) there was information related to hypertension or blood pressure (BP) in the study results. Of the 7486 abstracts found, 90 studies qualified for this review. Most studies reported a hypertension prevalence of 70% or higher (ranging from 29.4% to 93.4%). Despite this high prevalence, a substantial proportion of these populations did not receive adequate BP control, with most studies indicating a control rate of less than 40%. There was limited evidence on the prescription of antihypertensive therapies and medication adherence. There was a lack of studies from 4 of the 11 countries in the region. This review highlights that BP control in adults with diabetes remains a significant challenge in Southeast Asia. Given the ongoing epidemiological transition, and the increasing older population in this region who are likely to accumulate multiple chronic conditions complicating medication strategies, this review highlights the urgent need to improve BP management in those with diabetes., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: A core component of older adult health care assessment includes identifying fall risk, which also includes identifying those with subtle balance deficits., Objective: To compare body displacement of the Center of Pressure (CoP) and time held during the balance test. Also, to examine whether balance tests at baseline can predict falls after 6 months., Methods: A longitudinal study with 153 community-dwelling older adults, between 60-89 years old. Anteroposterior (AP) and mediolateral (ML) amplitude and velocity CoP displacements were assessed in four upright positions using a force platform: double-leg, semi-tandem, tandem, and single-leg stances, with a maximum duration of 30 s each. Adjusted repeated measures ANOVA were used to compare the differences among the balance positions. Comparisons between males and females were also conducted. Logistic regression adjusted for confounders was performed to verify whether upright balance tests can predict future falls., Results: As the base of support narrows, body sway increases. A decrease in stance time was observed across the balance stages, i.e., double-leg/semi-tandem versus tandem versus single-leg stances. The mean duration held in the single-leg stance was 14.8 s and for tandem was 22.2 s. Similar stance durations were observed for double-leg and semi-tandem stances. Males were able to maintain balance positions longer than females even with greater CoP displacement. ML amplitude of CoP displacement and the time held during tandem and single-leg positions were able to predict falls after 6 months (p < 0.05)., Conclusion: In clinical practice in which only stance time is recorded, it is possible to interchangeably use the double-leg or semi-tandem stance. To identify early signs of imbalance, we suggest setting a time limit for the balance test equal to or greater than 23 s, as 10 s appear to be insufficient to detect subtle balance deficits. The time maintenance on tandem and single-leg positions was able to predict future falls., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Research Ethics Committee at Clinical Hospital of Ribeirao Preto Medical School (CAAE: 50631615.9.0000.5440) and all participants signed the informed consent form to participate, following Helsinki’s declaration procedures for human research studies. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: The integrated care for older people (ICOPE) program, developed by the World Health Organization, serves as a public health initiative to maintain older adults' functional abilities and promote healthier aging. Here, we adapted the ICOPE approach to assess overall prevalence of frailty in rural and semi-urban areas. We also investigated health-related quality of life and physical activity and sedentary behavior in older people., Methods: The FRAGING multicenter cohort study was performed on screening days dedicated to older adults (≥65 years) without chronic disease in a rural area (RU) and in a semi-urban area (SU)., Results: The study included a total of 105 participants: 98.4% of participants were frail, with a mean of 4.3 [SD: 2.5] frailties per participant. RU participants had higher number of frailties (p = 0.02) and a higher percentage of frail participants in the dimensions of health-related quality of life (p < 0.0001), socioeconomical level (p = 0.008), colorectal cancer screening (p = 0.022), and tetanus booster doses (p = 0.008). Globally, women were less sedentary than men (p = 0.02) and engaged more in low physical activity (LPA) than men (p = 0.01). RU participants engaged more in LPA than SU participants (p = 0.03)., Conclusions: The prevalence of frailty is alarmingly underestimated in older adults without chronic disease. This study demonstrated the need to propose appropriate, validated screening tests that consider territorial issues and organization of care delivery. The ICOPE framework serves as a good startpoint for reorganizing person-centered healthcare pathways., (© 2024 Wiley Periodicals LLC.)

Aging is a complex process associated with multimorbidity. Hypertension, one of widespread states, is among main causes of age-related alterations in behavior, emotionality and sociability. We studied the effects of long-term isolated housing on anxiety, depressive-like and social behavior as well as changes in the adrenocortical and sympathetic systems in the aging normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). Ten-month-old male rats of both strains were subjected to 90-day isolated or group housing. Surprisingly, social isolation induced only mild effect on anxiety without influencing other affective-related behaviors. No effects of isolated housing on sociability or social novelty preferences were revealed. Despite the adrenal gland hypertrophy in the SHRs, corticosterone levels remained stable within the period of isolation but the expression of nuclear glucocorticoid receptor (Nr3c1) mRNA in the adrenals was lower in the SHR as compared to WKY rats. Pre-existing hypertension, associated with SHR genotype, did not significantly contribute to the effects of social isolation. The data suggest that the aged WKY and SHR rats are relatively resilient to chronic social stress associated with isolated housing., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: Identifying persons with HIV (PWH) at increased risk for Alzheimer's disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined., Design: We examined 92 PWH from the CHARTER Program, ages 45-68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years)., Results: At baseline, thinner pars opercularis cortex was associated with impaired recognition ( p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis ( p = 0.001) and thinner rostral middle frontal cortex ( p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall., Conclusions: Episodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.

The suprachiasmatic nucleus (SCN) in the hypothalamus regulates circadian timing system (CTS) by co-ordinating peripheral tissue clocks and extra-SCN oscillators in the brain. Aging disrupts the CTS, impairing physiological functions and reducing antioxidant defences, which contribute to neurodegeneration. The brain is vulnerable to oxidative damage due to its high metabolic activity, oxygen consumption, and levels of iron and lipids. Antioxidant enzymes, such as catalase (CAT), glutathione S-transferase (GST), superoxide dismutase (SOD), and lipid peroxidation (LPO), help against oxidative damage. In this study, we examined the temporal patterns of these antioxidant stress indicators in the SCN and extra-SCN brain regions (frontal cortex, cerebellum, and hippocampus) at various time points in male Wistar rats 3, 12, and 24 months. The rhythmicity of GST and LPO levels persisted across brain regions with aging, while CAT rhythmicity was lost in the SCN and hippocampus of older rats. SOD rhythmicity persisted in cortex, cerebellum, and hippocampus but was lost in the SCN. The daily rhythm parameters of CAT were affected most significantly, followed by SOD, GST, and LPO. Our findings demonstrate that aging leads to desynchronization of oxidative stress indicators potentially contributing to neurodegeneration and circadian dysfunction with varying effects across different brain tissues., Competing Interests: Declarations Conflict of interest Authors declare they have no conflict., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Brain structure, oxygenation and perfusion are important factors in aging. Coupling between regional cerebral oxygen consumption and perfusion also reflects functions of neurovascular unit (NVU). Their trajectories and sex differences during normal aging important for clinical interpretation are still not well defined. In this study, we aim to investigate the relationship between brain structure, functions and age, and exam the sex disparities., Method: A total of 137 healthy subjects between 20∼69 years old were enrolled with conventional MRI, structural three-dimensional T 1 -weighted imaging (3D-T 1 WI), 3D multi-echo gradient echo sequence (3D-mGRE), and 3D pseudo-continuous arterial spin labeling (3D-pCASL). Oxygen extraction fraction (OEF) and cerebral blood flow (CBF) were respectively reconstructed from 3D-mGRE and 3D-pCASL images. Cerebral metabolic rate of oxygen (CMRO 2 ) were calculated as follows: CMRO 2 =CBF·OEF·[H] a , [H] a =7.377 μmol/mL. Brains were segmented into global gray matter (GM), global white matter (WM), and 148 cortical subregions. OEF, CBF, CMRO 2 , and volumes of GM/WM relative to intracranial volumes (rel&#95;GM/rel&#95;WM) were compared between males and females. Generalized additive models were used to evaluate the aging trajectories of brain structure and functions. The coupling between OEF and CBF was analyzed by correlation analysis. P or P FDR < 0.05 was considered statistically significant., Results: Females had larger rel&#95;GM, higher CMRO 2 and CBF of GM/WM than males (P < 0.05). With control of sex, CBF of GM significantly declined between 20 and 32 years, CMRO 2 of GM declined subsequently from 33 to 41 years and rel&#95;GM decreased significantly at all ages (R 2 = 0.27, P < 0.001; R 2 = 0.17, P < 0.001; R 2 = 0.52, P < 0.001). In subregion analysis, CBF declined dispersedly while CMRO 2 declined widely across most subregions of the cortex during aging. Robust negative coupling between OEF and CBF was found in most of the subregions (r range = -0.12∼-0.48, P FDR < 0.05)., Conclusion: The sex disparities, age trajectories of brain structure and functions as well as the coupling of NVU in healthy individuals provide insights into normal aging which are potential targets for study of pathological conditions., Competing Interests: Declaration of competing interest I have nothing to declare., (Copyright © 2024. Published by Elsevier Inc.)

Vertebrate spermatogonial stem cells maintain sperm production over the lifetime of an animal, but fertility declines with age. Although morphological studies have informed our understanding of typical spermatogenesis, the molecular and cellular mechanisms underlying the maintenance and decline of spermatogenesis are not yet understood. We used single-cell RNA sequencing to generate a developmental atlas of the aging zebrafish testis. All testes contained spermatogonia, but we observed a progressive decline in spermatogenesis that correlated with age. Testes from some older males only contained spermatogonia and a reduced population of spermatocytes. Spermatogonia in older males were transcriptionally distinct from spermatogonia in testes capable of robust spermatogenesis. Immune cells including macrophages and lymphocytes drastically increased in abundance in testes that could not complete spermatogenesis. Our developmental atlas reveals the cellular changes as the testis ages and defines a molecular roadmap for the regulation of spermatogenesis., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Insects exhibit a remarkable ability to interact with inanimate objects to facilitate essential behaviors such as foraging, reproduction, shelter building, and defense. In this study, we assessed whether Drosophila interacted with inanimate objects when they were suspended on their wings and provided with a thermocol ball (foam ball). Drosophila indeed exhibited ball rolling behavior. We further examined the sexual dimorphism in this ball rolling-associated locomotor behavior. We carried out a ball rolling assay using 3-day-old male and female w1118 flies and measured the duration for which the flies could roll the ball without dropping it within a 10 min period. The ball was returned to the flies whenever they dropped it, and we calculated the number of times the ball was dropped within the 10 min duration. Females exhibited a longer ball holding duration than males. We also observed a decrease in ball holding duration and an increase in the number of times the ball was dropped by 15-day-old male and female flies than their younger counterparts. These results suggest sexual dimorphism and age-dependent alterations in Drosophila ball rolling-associated locomotor behavior., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Aims: Clinical data supports electroacupuncture (EA) as an effective treatment for female reproductive disorders especially gonadotropin abnormalities. This study aims to detect the mechanism of EA that improves the neuroendocrine defects particularly the luteinizing hormone (LH) surge failure in early reproductive aging females., Materials and Methods: Middle-aged ovariectomized rats primed with hormone were treated by EA at acupoints CV4 and SP6 and undergone LH assay. Morphological experiments detected the activation of Kiss1 cells in the anteroventral periventricular nucleus (AVPV). Using targeted liquid chromatography with tandem mass spectrometry (LC-MS/MS) and RNA-sequencing, we determined the concentrations of neurotransmitter metabolites and transcriptomics in AVPV., Key Findings: EA significantly increased c-Fos and c-Fos-positive Kiss1 cells in the middle-aged AVPV as well as the total and peak LH release. Targeted LC-MS/MS and RNA-sequencing of AVPV identified differential neurotransmitters in the middle-aged females including Acetylcholine chloride, 5-Hydroxyindole-3-aceticacid, Kynurenine, Histamine, L-Histidine and L-Glycine, while EA decreased the concentration of Acetylcholine chloride. Totally 1255 differentially expressed genes modulated by EA were strongly implicated in neurotransmitter transport and KEGG pathways involved neuroactive ligand-receptor interaction, glutamatergic and gamma-aminobutyric acid-mediated synapse. Specifically, the mRNAs associated with the LH surge such as hormone receptor Pgr, adrenoceptor Adra1a, neurotransmitter transporters Slc17a6 and Slc32a1, glutamate decarboxylase Gad2 and Kiss1 were markedly altered by EA., Significance: These findings showed that the age-related reduction of LH surge occurred via differential neurotransmitter metabolisms and altered transcriptions in AVPV, which proposed EA-based therapy for improving responsiveness of the hypothalamus to hormone in women with advanced age., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Japan, the world's most rapidly aging society, faces increasing financial strains related to personalized dementia care. The government has shifted its focus from prevention to coexistence with dementia, as outlined in the 2023 Basic Act on Dementia. Emphasis on financial inclusion aligns with the G20's 2019 "Fukuoka Policy Priorities on Aging and Financial Inclusion", which addresses financial exclusion due to cognitive decline and poor financial literacy. While economic activity among older adults is already hampered by legal challenges and risks associated with dementia, outcomes are expected to worsen as the assets of older adults with dementia are projected to reach 215 trillion JPY ($1.4 trillion USD) by 2030. Government measures and research in financial gerontology advocate for protecting older adults and promoting flexible financial practices. Enhanced efforts and shared research outcomes are crucial for Japan to be a leader as an advanced aging society.

Rapid urbanization brought lots of serious environmental contamination, including the accumulation of heavy metals, acid rain, and the emission of tire wear particles (TWPs), with detrimental effects for terrestrial ecosystems. Nevertheless, how naturally aged TWPs affect the mobilization of heavy metals in soils under acid rain is still unclear. Here, we investigate the adsorption and transport mechanisms of Pb(II) co-existing with acid rainwater in soil-TWP mixtures via batch experiments, column experiments and modeling. Results showed that photoaged TWP significantly prolonged the Pb(II) adsorption equilibrium time (1 to 16 h) and enhanced the Pb(II) adsorption capacity of soils. Soil column profiles confirmed that TWP effectively boosted the initial accumulation of lead in the topsoil and thus impeded the downward transport of lead. The retardation factor (R) estimated by the linear two-site sorption model (TSM) fitting the Pb(II) breakthrough curves gradually increased from 1.098 to 16.38 in soils with TWP (0-10 %). Comparative results of linear or nonlinear TSM suggested nonlinear sorption replacing linear sorption as the main Pb(II) sorption mechanism under 1 % and 10 % TWP. This research provides significant insights into the implications of TWP on the Pb(II) retention behaviors and highlights the severer potential remobilization risks of Pb(II) in urban soils under different acid rain environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Dewatering is an indispensable link in sludge treatment, but its effect on the microplastics (MPs) remains inadequately understood. This study investigated the physicochemical changes and leaching behavior of MPs during the mechanical dewatering of sludge, as well as the impact of MP leachates on activated sludge (AS). After sludge dewatering, MPs exhibit rougher surfaces, decreased sizes and altered functional groups due to the addition of dewatering agents and the application of mechanical force. Meanwhile, plastic additives, depolymerization products, and derivatives of their interactions are leached from MPs during sludge dewatering process. The concentration of MP-based leachates in sludge is 2-25 times higher than that in water. The enhancement of pH and ionic strength caused by dewatering agents induces the release of MP leachates enriched with protein-like, fulvic acid-like, and soluble microbial by-product-like substances. The reflux of MP leachates in sludge dewatering liquor to the wastewater treatment system negatively impacts AS, leading to a decrease in COD removal rate and inhibition of the extracellular polymeric substances secretion. More importantly, MP leachates cause oxidative stress to microbial cells and alter the microbial community structure of AS at the phylum and genus levels. These findings confirm that MPs undergo aging and leaching during sludge dewatering process, and MP leachates may negatively affect the wastewater treatment system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The immune system is a major regulatory system of the body, that is composed of immune cells, immune organs, and related signaling factors. As an organism ages, observable age-related changes in the function of the immune system accumulate in a process described as 'immune aging. Research has shown that the impact of aging on immunity is detrimental, with various dysregulated responses that affect the function of immune cells at the cellular level. For example, increased aging has been shown to result in the abnormal chemotaxis of neutrophils and decreased phagocytosis of macrophages. Age-related diminished functionality of immune cell types has direct effects on host fitness, leading to poorer responses to vaccination, more inflammation and tissue damage, as well as autoimmune disorders and the inability to control infections. Similarly, age impacts the function of the immune system at the organ level, resulting in decreased hematopoietic function in the bone marrow, a gradual deficiency of catalase in the thymus, and thymic atrophy, resulting in reduced production of related immune cells such as B cells and T cells, further increasing the risk of autoimmune disorders in the elderly. As the immune function of the body weakens, aging cells and inflammatory factors cannot be cleared, resulting in a cycle of increased inflammation that accumulates over time. Cumulatively, the consequences of immune aging increase the likelihood of developing age-related diseases, such as Alzheimer's disease, atherosclerosis, and osteoporosis, among others. Therefore, targeting the age-related changes that occur within cells of the immune system might be an effective anti-aging strategy. In this article, we summarize the relevant literature on immune aging research, focusing on its impact on aging, in hopes of providing new directions for anti-aging research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Mechanistic studies of the effects of environmental risk factors have been exploring the potential role of microRNA(miRNAs) as a possible pathway to clinical disease. In this study we examine whether levels of toenail metals are associated with changes in extracellular miRNA(ex-miRNA) expression., Methods: We used data derived from the Normative Aging Study from 1996 to 2014 to conduct our analyses. We looked at associations between measured toenail metals: arsenic, cadmium, lead, manganese, and mercury and 282 ex-miRNAs in this population using canonical correlation analyses (CCAs) and longitudinal median regression. We adjusted for covariates such as age, education, body mass index, drinking and smoking behaviors, diabetes, and where available, seafood consumption. The p-values obtained from regression analyses were corrected for multiple comparisons. Ex-miRNAs identified to be associated with toenail metal levels were further examined using pathway analyses., Results: Our dataset included 937 observations from 589 men with an average age of 72.9 years at baseline. Both our correlation and regression analyses identified lead and cadmium as exposures most strongly associated with ex-miRNA expression. Numerous ex-miRNAs were identified as being associated with toenail metal levels. miR-27b-3p, in particular, was found to have high correlation with the first canonical dimension in the CCA and was significantly associated with cadmium in the regression analysis. Pathway analyses revealed messenger RNA (mRNA) targets for the ex-miRNAs that were associated with a number of clinical disorders including cancer, cardiovascular disease, and neurological disorders, etc. CONCLUSION: Toenail metals were associated with changes in ex-miRNA levels in both correlational and regression analyses. The ex-miRNAs identified can be linked to a variety of clinical disorders. Further studies are required to validate these findings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Joel Schwartz and Andrea Baccarelli reports financial support was provided by National Institute of Environmental Health Sciences. Feiby Nassan reports a relationship with Novo Nordisk Inc that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Consumption of saturated fat-enriched diets during adolescence has been closely associated with the reduction of hippocampal synaptic plasticity and the impairment of cognitive function. Nevertheless, the effect of long-term intake of these foods has not yet been studied. In the present study, we have investigated the effect of a treatment, lasting for 40 weeks, with a diet enriched in saturated fat (SOLF) on i) spatial learning and memory, ii) hippocampal synaptic transmission and plasticity, and iii) hippocampal gene expression levels in aged male and female mice. Our findings reveal that SOLF has a detrimental impact on spatial memory and synaptic plasticity mechanisms, such as long-term potentiation (LTP), and downregulates Gria1 expression specifically in males. In females, SOLF downregulates the gene expression of Gria1/2/3 and Grin1/2A/2B glutamate receptor subunits as well as some proinflammatory interleukins. These findings highlight the importance of considering sex-specific factors when assessing the long-term effects of high-fat diets on cognition and brain plasticity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Bipolar disorder (BD) is hypothesized to be associated with accelerated biological aging. Telomere length (TL) is a biomarker of aging, and although TL decreases with each cell division, the rate of telomere shortening may be affected by inflammation. We aimed to investigate whether TL is decreased in BD patients and to determine the association between TL and inflammatory markers in such patients., Methods: 137 BD patients and 118 healthy controls (HCs) were recruited. Leukocyte TL and plasma levels of cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-8, IL-6, IL-10, transforming growth factor (TGF)-β1], C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF) were assessed., Results: TL did not differ significantly between the BD patients and HCs after adjustment for potential confounding factors (P = 0.79). TL was significantly negatively associated with age (β = -0.007, P < 0.001). In addition, log TNF-α levels were significantly negatively associated with TL (P = 0.009), in both the BD patients (P = 0.02) and HCs (P = 0.05)., Conclusion: We found a significant association between TNF-α levels and TL shortening in both BD patients and HCs. However, BD patients did not display increased TL shortening relative to HCs. Studies that involve larger sample sizes and control for the heterogeneity of BD participants will be needed., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Maternal smoking during pregnancy (MSDP) is significantly linked to the short- or long-term health of offspring. However, little research has examined whether MSDP affect the aging rate of offspring., Methods: This study used questionnaires to determine out whether the participants' mothers smoked when they were pregnant. For evaluating aging rate, we used the following several outcome measures: telomere length, frailty index, cognitive function, homeostatic dysregulation score, KDM-age, age-related hospitalization rate, premature death, and life expectancy., Result: After adjusting for covariates, we found that the offspring of the MSDP group had significantly shorter telomere length in adulthood by 0.8 % (β = -0.008,95%CI:-0.009 to -0.006) compared with non-MSDP group. Compared to the non-MSDP group, participants in MSDP group showed higher levels of homeostatic dysregulation (β = 0.015,95%CI: 0.007-0.024) and were frailer (β = 0.008,95%CI:0.007-0.009). The KDM age increased by 0.100 due to MSDP (β = 0.100,95 % CI:0.018-0.181), and the age acceleration of KDM algorithm also increases significantly (β = 0.101, 95%CI:0.020-0.183). Additionally, we found that the risk of aging-related hospitalizations was significantly higher than the non-MSDP group by 10.4 %(HR = 1.104,95%CI:1.066-1.144). Moreover, MSDP group had a 12.2 % increased risk of all-cause premature mortality (HR = 1.122,95%CI:1.064-1.182) and a significant risk of lung cancer-specific premature mortality increased by 55.4 %(HR = 1.554,95%CI:1.346-1.793). In addition, participants in the MSDP group had significantly decreased cognitive function and shorter life expectancies than those in non-MSDP group., Conclusion: Our findings indicated a significant association between MSPD and accelerated aging, elevated hospitalization rates, increased premature mortality rates, and reduced life expectancies in offspring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The accumulating evidence has made it clear that iron overload is a crucial mechanism in bone loss. Protocatechualdehyde (PCA) has also been used to prevent osteoporosis in recent years. Whether PCA can reverse the harmful effects of iron overload on bone mass in aged rats is still unknown. Therefore, this study aimed to assess the role of PCA in iron overload-induced bone loss in senile rats. In the aged rat model, we observed that iron overload affects bone metabolism and bone remodeling, manifested by bone loss and decreased bone mineral density. The administration of PCA effectively mitigated the detrimental effects caused by iron overload, and concomitant reduction in MDA serum levels and elevation of SOD were noted. In addition, PCA-treated rats were observed to have significantly increased bone mass and elevated expression of SIRT3，BMP2，SOD2 and reduced expression of TNF-α in bone tissue. We also observed that PCA was able to reduce oxidative stress and inflammation and restore the imbalance in bone metabolism. When MC3T3-E1 and RAW264.7 cells induced osteoblast and osteoclasts differentiation, PCA intervention could significantly recover the restriction of osteogenic differentiation and up-regulation of osteoclast differentiation treated by iron overload. Further, by detecting changes in ROS, SOD, MDA, expression of SIRT3 and mitochondrial membrane potentials, we confirm that the damage caused to cells by iron overload is associated with decreased SIRT3 activity, and that 3-TYP have similar effects on oxidative stress caused by FAC. In conclusion, PCA can resist iron overload-induced bone damage by improving SIRT3 activity, anti-inflammatory and anti-oxidative stress., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Heart disease is the leading cause of mortality in developed countries, and novel regenerative procedures are warranted. Direct cardiac conversion (DCC) of adult fibroblasts can create induced cardiomyocytes (iCMs) for gene and cell-based heart therapy, and in addition to holding great promise, still lacks effectiveness as metabolic and age-associated barriers remain elusive. Here, by employing MGT (Mef2c, Gata4, Tbx5) transduction of mouse embryonic fibroblasts (MEFs) and adult (dermal and cardiac) fibroblasts from animals of different ages, we provide evidence that the direct reprogramming of fibroblasts into iCMs decreases with age. Analyses of histone posttranslational modifications and ChIP-qPCR revealed age-dependent alterations in the epigenetic landscape of DCC. Moreover, DCC is accompanied by profound mitochondrial metabolic adaptations, including a lower abundance of anabolic metabolites, network remodeling, and reliance on mitochondrial respiration. In vitro metabolic modulation and dietary manipulation in vivo improve DCC efficiency and are accompanied by significant alterations in histone marks and mitochondrial homeostasis. Importantly, adult-derived iCMs exhibit increased accumulation of oxidative stress in the mitochondria and activation of mitophagy or dietary lipids; they improve DCC and revert mitochondrial oxidative damage. Our study provides evidence that metaboloepigenetics plays a direct role in cell fate transitions driving DCC, highlighting the potential use of metabolic modulation to improve cardiac regenerative strategies., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

The aging of the central nervous system(CNS) is a primary contributor to neurodegenerative diseases in older individuals and significantly impacts their quality of life. Neuroinflammation, characterized by activation of microglia(MG) and release of cytokines, is closely associated with the onset of these neurodegenerative diseases. The activated status of MG is modulated by specifically programmed metabolic changes under various conditions. Succinylation, a novel post-translational modification(PTM) mainly involved in regulating mitochondrial energy metabolism pathways, remains unknown in its role in MG activation and aging. In the present study, we found that succinylation levels were significantly increased both during aging and upon lipopolysaccharide-induced(LPS-induced) MG activation undergoing metabolic reprogramming. Up-regulated succinylation induced by sirtuin 5 knockdown(Sirt5 KD) in microglial cell line BV2 resulted in significant up-regulation of aging-related genes, accompanied by impaired mitochondrial adaptability and a shift towards glycolysis as a major metabolic pathway. Furthermore, after LPS treatment, Sirt5 KD BV2 cells exhibited increased generation of reactive oxygen species(ROS), accumulation of lipid droplets, and elevated levels of lipid peroxidation. By employing immunoprecipitation, introducing point mutation to critical succinylation sites, and conducting enzyme activity assays for succinate dehydrogenase(SDH) and trifunctional enzyme subunit alpha(ECHA), we demonstrated that succinylation plays a regulatory role in modulating the activities of these mitochondrial enzymes. Finally, down-regulation the succinylation levels achieved through administration of succinyl phosphonate(SP) led to amelioration of MG senescence in vitro and neuroinflammation in vivo. To our knowledge, our data provide preliminary evidence indicating that up-regulated succinylation modifications elicit a senescence phenotype in MG through alterations in energy metabolism. Moreover, these findings suggest that manipulation of succinylation levels may offer valuable insights into the treatment of aging-related neuroinflammation., Competing Interests: Declarations Ethical approval All procedures were in accordance with the Dalian Medical University guidelines for the proper care and use of laboratory animals and were approved by the Laboratory Animal Care and Use Committee of Dalian Medical University. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

To improve transitions in care, a new patient navigation (PN) program was introduced to support older adults with complex care needs transition from hospital to home. The patient navigator is a community social worker embedded in the hospital's care teams. A cohort observational design was used to conduct the study by analysing the patient navigator's clinical notes and hospital's administrative data to describe the characteristics of patients, scope of the patient navigator's activities, and patient outcomes. Ninety patients were assigned to the patient navigator's caseload (November 2019-November 2021) in which the average age was 78.9 (range 55-95). The most frequent PN intervention types were referrals to community services (66%, n = 59) and discharge planning (61%, n = 55). The patient navigator supported 66% patients ( n = 59) in returning home and provided follow-up care for 74 days (average). This study provides important insights into the patient navigator's role to guide decision makers in implementing PN programs for older adults in a hospital setting.

Several crucial acceleration periods exist during aging process. Epigenetic clocks, serving as indicators of aging, are influenced by genetic factors. Investigating how the genetic contributions on these clocks change with age may provide novel insights into the aging process. In this study, based on 1084 adult twins from the Chinese National Twin Registry (CNTR), we established structural equation models (SEMs) to evaluate the trends in genetic influence with aging for epigenetic clocks, which include PC-Horvath, PC-Hannum, PC-PhenoAge, PC-GrimAge, and DunedinPACE. A decline in overall heritability was observed for all five clocks from ages 31 to 70, with a relatively stable trend at first. Subsequently, apart from PC-GrimAge, the other four clocks displayed a more evident drop in heritability: DunedinPACE and PC-PhenoAge experienced a clear decline between 55 and 65 years, while PC-Horvath and PC-Hannum showed a similar decrease between 60 and 70 years. In contrast, the heritability of PC-GrimAge remained stable throughout. An analysis of methylation sites (CpGs) from these clocks identified 41, 26, 4, and 36 CpG sites potentially underlying heritability changes in DunedinPACE, PC-Horvath, PC-Hannum, and PC-PhenoAge, respectively. Data from the CNTR were collected through two surveys in 2013 and 2018. Based on 308 twins with longitudinal data, declines in genetic components were observed at follow-up compared to baseline, with significant decreases in the four PC-clocks. DunedinPACE peaked in 5-year longitudinal genetic contribution changes at age 55-60, while PC-clocks consistently peaked at age 50-55. These findings may offer novel insights into the role of genetic variations in aging., (© 2024 The Author(s). Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

There is an ongoing debate about the ethics of research on lifespan extension: roughly, using medical technologies to extend biological human lives beyond the current "natural" limit of about 120 years. At the same time, there is an exploding interest in the use of artificial intelligence (AI) to create "digital twins" of persons, for example by fine-tuning large language models on data specific to particular individuals. In this paper, we consider whether digital twins (or digital doppelgängers, as we refer to them) could be a path toward a kind of life extension-or more precisely, a kind of person extension-that does not rely on biological continuity. We discuss relevant accounts of consciousness and personal identity and argue that digital doppelgängers may at least help us achieve some of the aims or ostensible goods of person-span extension, even if they may not count as literal extensions of our personhood on dominant philosophical accounts. We also consider relational accounts of personhood and discuss how digital doppelgängers may be able to extend personhood in a relational sense, or at least secure some of the goods associated with relevant relationships. We conclude by suggesting that a research program to investigate such issues is relevant to ongoing debates about the ethics of extending the human lifespan.

Alzheimer's disease (AD) is a leading cause of dementia, disability, and death in the elderly. While the etiology of AD is unknown, there are several established risk factors for the disease including, aging, female sex, and genetics. However, specific genetic mutations only account for a small percentage (1-5%) of AD cases and the much more common sporadic form of the disease has no causative genetic basis, although certain risk factor genes have been identified. While the genetic code remains static throughout the lifetime, the activation and expression levels of genes change dynamically over time via epigenetics. Recent evidence has emerged linking changes in epigenetics to the pathogenesis of AD, and epigenetic alterations also modulate cognitive changes during physiological aging. Aging is the greatest risk factor for the development of AD and two-thirds of all AD patients are women, who experience an increased rate of symptom progression compared to men of the same age. In humans and other mammalian species, males and females experience aging differently, raising the important question of whether sex differences in epigenetic regulation during aging could provide an explanation for sex differences in neurodegenerative diseases such as AD. This review explores distinct epigenetic changes that impact memory function during aging and AD, with a specific focus on sexually divergent epigenetic alterations (in particular, histone modifications) as a potential mechanistic explanation for sex differences in AD., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.