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Dietary restriction (DR) is a potent method to enhance lifespan and healthspan, but individual responses are influenced by genetic variations. Understanding how metabolism-related genetic differences impact longevity and healthspan are unclear. To investigate this, we used metabolites as markers to reveal how different genotypes respond to diet to influence longevity and healthspan traits. We analyzed data from Drosophila Genetic Reference Panel (DGRP) strains raised under AL and DR conditions, combining metabolomic, phenotypic, and genome-wide information. We employed two computational and complementary methods across species-random forest modeling within the DGRP as our primary analysis and Mendelian randomization in human cohorts as a secondary analysis. We pinpointed key traits with cross-species relevance as well as underlying heterogeneity and pleiotropy that influence lifespan and healthspan. Notably, orotate was linked to parental age at death in humans and blocked the DR lifespan extension in flies, while threonine supplementation extended lifespan, in a strain- and sex-specific manner. Thus, utilizing natural genetic variation data from flies and humans, we employed a systems biology approach to elucidate potential therapeutic pathways and metabolomic targets for diet-dependent changes in lifespan and healthspan.

Abstract Vitality Forms (VFs) constitute the dynamic essence of human actions, providing insights into how individuals engage in activities. The ability to perceive and express VFs during interpersonal interactions is pivotal for understanding others’ intentions, behaviors, and fostering effective social communication. Despite their ubiquity in all actions, research exploring the role of VFs in neurodivergent conditions related to social and communicative skills, particularly in autism, remains limited. This study aims to investigate the expression of different VFs during the execution of both social and non-social actions in children with an Autism Spectrum Condition (ASC) in comparison to neurotypical children (NT). ASC children and NT children were asked to move a small bottle either towards a target point (non-social context) or moving it towards a receiver (social context) with different VFs specifically neutral, gentle, or rude. Videotaped tasks were subsequently analyzed to study kinematic parameters characterizing VFs. Our results highlighted three main findings: (1) overall, ASC children are able to tune the motor profile of their actions, effectively conveying both gentle and rude VFs; (2) distinct kinematic parameters in the execution of VFs are able to distinguish autistic children from NT children; (3) the social context significantly influences the child’s ability to express positive and negative VFs in autism. Taken together, these findings provide new insights to understand how VFs contribute to the complex dynamics of social communication in neurodivergent autistic children, providing a valuable contribution for future interventions and support strategies.

Linguistic strategies humans use for communication are designed to meet the informational needs of their addressees. Speakers not only adapt their speech but also increase the rate of iconic gestures to enhance the clarity of a message for children. Although sign languages allow signers to take advantage of iconicity far more than what is possible in speech, little is known about whether signers use iconicity as a strategy in child-directed communication. In the present study, we used automatic video pose estimation to analyze descriptions aimed at a child (12yo) vs. an adult produced by 7 deaf adult signers of Italian Sign Language. Overall, signers used iconic constructions more than lexical signs and with comparable frequency in descriptions for both age groups. However, iconic constructions were longer in duration for children. Thus, the present study presents the first evidence that, unlike speakers, signers do not modulate quantitative but only qualitative aspects of iconicity for children.

The non-thermal mechanisms, underlying the damage induced on human cells by radiofrequency electromagnetic fields (RF-EMFs), are still unclear and only few studies reported about the effect of RFEMFs on self-renewal of neural progenitor cells. In this research, we investigated the influence of low-intensity RF-EMFs on Olfactory Ensheathing Cell (OEC) cultures, typical glia cells showing characteristics of stem cells. Cell cultures were exposed, in far-field condition, at 900 MHz continuous and amplitude modulated EMFs for 10, 15 and 20 min at 37°C. The expression of OEC marker (S-100), stem cell marker (Nestin), cytoskeletal proteins (GFAP and Vimentin), apoptotic pathway activation by Caspase-3 cleavage and cell viability, were evaluated. Surprisingly 20 min of exposure to continuous or amplitude modulated 900 MHz EMF induced a different and significant decrease in cell viability, some dynamic changes in the expression of the analysed markers and in the activation of the apoptotic pathway.

Growing scientific evidence suggests a link between the expression of toll-like receptor 4 (TLR4) and cervical cancer carcinogenesis. Specifically, a close relation between TLR4 expression and FIGO stage, lymph node metastases, and tumor size has been reported in cervical cancer. In the present study, we aimed to evaluate the relationship between TLR4 expression levels and human papillomavirus (HPV) infection and/or high-risk (hr) HPV integration status in patients with a histological diagnosis of high-grade squamous intraepithelial lesion (H-SIL), and squamous cell carcinoma (SCC) of the uterine cervix. Sixty biopsies of cervical neoplasia, comprising H-SIL (n = 20) and SCC (n = 40), were evaluated for TLR4 expression by immunohistochemistry. All samples were positive for high-risk HPV as confirmed by in situ hybridization (ISH) and broad-spectrum PCR followed by Sanger sequencing analysis. The intensity of TLR4 staining was higher in tissues negative for intraepithelial lesion or malignancy (NILM) than in H-SIL, and further reduced in SCC. Moreover, statistically significant differences have been observed in the percentage of TLR4 expression between NILM and H-SIL and between H-SIL and SCC, with higher percentages of expression in H-SIL than in SCC. Our results showed a significant downregulation of TLR4 in HPV-related H-SIL and SCC, compared to NILM. These data support the hypothesis that TLR4 expression is suppressed in HPV-driven oncogenesis.

Abstract Dietary restriction (DR) is a potent method to enhance lifespan and healthspan, but individual responses are influenced by genetic variations. Understanding how metabolism-related genetic differences impact longevity and healthspan are unclear. To investigate this, we used metabolites as markers to reveal how different genotypes respond to diet to influence longevity and healthspan traits. We analyzed data from Drosophila Genetic Reference Panel (DGRP) strains raised under AL and DR conditions, combining metabolomic, phenotypic, and genome-wide information. We employed two computational and complementary methods across species—random forest modeling within the DGRP as our primary analysis and Mendelian randomization in human cohorts as a secondary analysis. We pinpointed key traits with cross-species relevance as well as underlying heterogeneity and pleiotropy that influence lifespan and healthspan. Notably, orotate was linked to parental age at death in humans and blocked the DR lifespan extension in flies, while threonine supplementation extended lifespan, in a strain- and sex-specific manner. Thus, utilizing natural genetic variation data from flies and humans, we employed a systems biology approach to elucidate potential therapeutic pathways and metabolomic targets for diet-dependent changes in lifespan and healthspan.

Introduction: Metastatic breast cancer (MBC) presents an enduring and significant challenge for affected women, requiring sustained commitment over the years. Case Presentation: This paper presents a case of a woman affected by bone and visceral MBC with a very long 20-year survival, excellent quality of life, and high resilience. She is now 51 years old and underwent quadrantectomy for breast cancer in 2005, and in 2013, she developed a recurrence with bone and liver metastases. Despite the widespread stage of the disease with visceral compromise, the patient was treated with a multidisciplinary approach that included surgery, chemotherapy, radiotherapy, hormone therapy, bone target agents, metabolic radiotherapy, and ozone therapy for medication-related osteonecrosis of the jaw. Multidisciplinary management results in a complete clinical and metabolic response to treatment in a visceral metastatic setting. Conclusion: This report supports the possibility of achieving unusual survival outcomes in patients with MBC. This study also highlights the importance of resilience in breast cancer patients who continue to manage their disease and pursue treatment for over 2 decades. Understanding these resilience factors can improve clinical practice and support patients’ long-term care.

Endogenous retroviruses (ERVs) are remnants of ancient parasitic infections and comprise sizable portions of most genomes. Although epigenetic mechanisms silence most ERVs by generating a repressive environment that prevents their expression (heterochromatin), little is known about mechanisms silencing ERVs residing in open regions of the genome (euchromatin). This is particularly important during embryonic development, where induction and repression of distinct classes of ERVs occur in short temporal windows. Here, we demonstrate that transcription-associated RNA degradation by the nuclear RNA exosome and Integrator is a regulatory mechanism that controls the productive transcription of most genes and many ERVs involved in preimplantation development. Disrupting nuclear RNA catabolism promotes dedifferentiation to a totipotent-like state characterized by defects in RNAPII elongation and decreased expression of long genes (gene-length asymmetry). Our results indicate that RNA catabolism is a core regulatory module of gene networks that safeguards RNAPII activity, ERV expression, cell identity, and developmental potency.