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The study of age-related biomarkers from different biofluids and tissues within the same individual might provide a more comprehensive understanding of age-related changes within and between compartments as these changes are likely highly interconnected. Understanding age-related differences by compartments may shed light on the mechanism of their reciprocal interactions, which may contribute to the phenotypic manifestations of aging. To study such possible interactions, we carried out a targeted metabolomic analysis of plasma, skeletal muscle, and urine collected from healthy participants, age 22-92 years, and identified 92, 34, and 35 age-associated metabolites, respectively. The metabolic pathways that were identified across compartments included inflammation and cellular senescence, microbial metabolism, mitochondrial health, sphingolipid metabolism, lysosomal membrane permeabilization, vascular aging, and kidney function., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Although aging is a physiological process to which all organisms are subject, the presence of obesity and type 2 diabetes accelerates biological aging. Recent studies have demonstrated the causal relationships between dietary interventions suppressing obesity and type 2 diabetes and delaying the onset of age-related endocrine changes. Curcumin, a natural antioxidant, has putative therapeutic properties such as improving insulin sensitivity in obese mice. However, how curcumin contributes to maintaining insulin homeostasis in aged organisms largely remains unclear. Thus, the objective of this study is to examine the pleiotropic effect of dietary curcumin on insulin homeostasis in a diet-induced obese (DIO) aged mouse model. Aged (18-20 months old) male mice given a high-fat high-sugar diet supplemented with 0.4% (w/w) curcumin (equivalent to 2 g/day for a 60 kg adult) displayed a different metabolic phenotype compared to mice given a high-fat high-sugar diet alone. Furthermore, curcumin supplementation altered hepatic gene expression profiling, especially insulin signaling and senescence pathways. We then mechanistically investigated how curcumin functions to fine-tune insulin sensitivity. We found that curcumin supplementation increased hepatic insulin-degrading enzyme (IDE) expression levels and preserved islet integrity, both outcomes that are beneficial to preserving good health with age. Our findings suggest that the multifaceted therapeutic potential of curcumin can be used as a protective agent for age-induced metabolic diseases.

In mice, cellular senescence and senescence-associated secretory phenotype (SASP) positively contribute to cutaneous wound healing. In this proof-of-concept study, we investigated the expressions of p16, p21, and other senescence-associated biomarkers during human wound healing in 24 healthy subjects using a double-biopsy experimental design. The first punch biopsy created the wound and established the baseline. The second biopsy, concentric to the first and taken several days after wounding, was used to probe for expression of biomarkers by immunohistochemistry and RNA FISH. To assess the effects of age, we recruited 12 sex-matched younger (30.2 ± 1.3 years) and 12 sex-matched older (75.6 ± 1.8 years) subjects. We found that p21 and p53, but not p16, were induced during healing in younger, but not older subjects. A role for Notch signaling in p21 expression was inferred from the inducible activation of HES1. Further, other SASP biomarkers such as dipeptidyl peptidase-4 (DPP4) were significantly induced upon wounding in both younger and older groups, whereas matrix metallopeptidase 9 (MMP9) was induced only in the younger group. Senescence-associated β-galactosidase (SA-β-gal) was not detectable before or after wounding. This pilot study suggests the possibility that human cutaneous wound healing is characterized by differential expression of p21 and p53 between younger and older subjects., (© 2021 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Objective Insulin-like growth factor-binding protein-2 (IGFBP-2) concentrations are low in subjects with metabolic syndrome and type 2 diabetes. Intriguingly, recent studies have demonstrated an association between high IGFBP-2 concentrations and increased mortality not only in populations with certain types of cancer, but also in relatively healthy populations. We evaluated the role of IGFBP-2 in relation to BMI and mortality. Design and Participants BMI, insulin sensitivity, insulin-like growth factor 1 (IGF-I) and IGFBP-2 were assessed repeatedly in 539 participants of the Baltimore Longitudinal Study of Aging around the ages of 55, 65 and 75 years. Results IGFBP-2 concentrations positively correlated with insulin sensitivity and inversely with BMI, both at baseline and follow-up. Independent of IGF-I, sex, BMI and insulin sensitivity, circulating IGFBP-2 levels positively correlated with age (P < 0.001). Changes over time in BMI were associated with an inverse correlation in IGFBP-2 concentrations. Furthermore, we found indications of a relationship between low baseline IGFBP-2 levels and mortality. Remarkably, after adjustment for insulin sensitivity, the opposite association was found, as a unit increase of log(IGFBP2) was associated with an increase in the log hazard by 1.43 (95% CI: 0.3-2.6). This accounted for both baseline (P = 0.02) as well as serial (P < 0.001) measurements of IGFBP2. Finally, in this longitudinal study, we found that IGF-I concentrations increased with age (0.82 ± 0.2 (µg/L)/year, P < 0.001). Conclusion This is the first study investigating the relationship between IGFBP-2 levels and age in a longitudinal setting. Serum IGFBP-2 levels increase with age after the age of 50 years and evolve in parallel with insulin sensitivity. IGFBP-2 may therefore be a potential marker for insulin sensitivity. We further show that IGFBP-2 levels can predict mortality in this aging population. However, its predictive value for mortality can only be interpreted in relation to insulin sensitivity. After adjustment for insulin sensitivity, high IGFBP-2 levels are predictive of increased mortality.

Background: Growth and differentiation factors 8 (GDF8) and 11 (GDF11) have attracted attention as targets for rejuvenating interventions. The biological activity of these proteins may be affected by circulating antagonists such as their respective prodomains, follistatin (FST315), WFIKKN1, and WFIKKN2. Reports of the relationship of GDF8 and GDF11 and their antagonists with aging and aging phenotypes such as skeletal muscle strength have been conflicting possibly because of difficulties in measuring these proteins and polypeptides., Methods: Plasma GDF8 and GDF11 and their antagonists were measured using a multiplexed selected reaction monitoring assay and liquid chromatography-tandem mass spectrometry in 160 healthy adults aged 22-93 years. Quadriceps strength was measured by knee extensor torque using isokinetic dynamometry., Results: Spearman correlations with age were the following: GDF11 prodomain (r = .30, p = .001), GDF11 mature protein (r = .23, p = .004), FST315 (r = .32, p < .0001), WFIKKN1 (r = -.21, p = 0.008), and WFIKKN2 (r = .18, p = .02). Independent of age, FST315 and WFIKKN1 were negatively associated with knee strength (p = .02, p = .03, respectively) in a multivariable model that included both GDF8 and GDF11 mature proteins., Conclusions: When measured by an antibody-free selected reaction monitoring assay, GDF8, GDF11, and their antagonists are found in the circulation in the ng/mL range. In healthy adults, plasma GDF11 and antagonists FST315, WFIKKN1, and WFIKKN2 differed by age. Antagonists of GDF8 and GDF11, but not GDF8 and GDF11, were independently associated with skeletal muscle strength. Further work is needed to characterize the relationship of these protein and polypeptides with sarcopenia-related phenotypes such as physical function and walking disability.

Aging and diabetes mellitus are 2 well-known risk factors for cardiovascular disease (CVD). During the past 50 years, there has been an dramatic increase in life expectancy with a simultaneous increase in the prevalence of diabetes mellitus in the older population. This large number of older individuals with diabetes mellitus is problematic given that CVD risk associated with aging and diabetes mellitus. In this review, we summarize epidemiological data relating to diabetes mellitus and CVD, with an emphasis on the aging population. We then present data on hyperglycemia as a risk factor for CVD and review the current knowledge of age-related changes in glucose metabolism. Next, we review the role of obesity in the pathogenesis of age-related glucose dysregulation, followed by a summary of the results from major randomized controlled trials that focus on cardiovascular risk reduction through glycemic control, with a special emphasis on older adults. We then conclude with our proposed model of aging that body composition changes and insulin resistance link possible dysregulation of physiological pathways leading to obesity and diabetes mellitus-both forms of accelerated aging-and risks for CVD.

During ageing, the secretory patterns of the hormones produced by the hypothalamic-pituitary axis change, as does the sensitivity of the axis to negative feedback by end hormones. Additionally, glucose homoeostasis tends towards disequilibrium with increasing age. Along with these endocrine alterations, a loss of bone and muscle mass and strength occurs, coupled with an increase in fat mass. In addition, ageing-induced effects are difficult to disentangle from the influence of other factors that are common in older people, such as chronic diseases, inflammation, and low nutritional status, all of which can also affect endocrine systems. Traditionally, the decrease in hormone activity during the ageing process has been considered to be detrimental because of the related decline in bodily functions. The concept of hormone replacement therapy was suggested as a therapeutic intervention to stop or reverse this decline. However, clearly some of these changes are a beneficial adaptation to ageing, whereas hormonal intervention often causes important adverse effects. In this paper, we discuss the effects of age on the different hypothalamic-pituitary-hormonal organ axes, as well as age-related changes in calcium and bone metabolism and glucose homoeostasis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Age-related changes in testosterone levels in older persons and especially in women have not been fully explored. The objective of this study was to describe age-related trajectories of total testosterone (TT), ammonium sulfate precipitation-measured bioavailable testosterone (mBT), and sex hormone-binding glycoprotein (SHBG) in men and women from the Baltimore Longitudinal Study of Aging, with special focus on the oldest adults., Methods: Participants included 788 White men and women aged 30-96 years with excellent representation of old and oldest old, who reported not taking medications known to interfere with testosterone. Longitudinal data were included when available. TT, mBT, and SHBG were assayed. Age-related trajectories of mBT were compared with those obtained using calculated bioavailable testosterone (cBT). Generalized least square models were performed to describe age-related trajectories of TT, mBT, and SHBG in men and women., Results: mBT linearly declines over the life span and even at older ages in both sexes. In men, TT remains quite stable until the age of 70 years and then declines at older ages, whereas in women TT progressively declines in premenopausal years and slightly increases at older ages. Differences in age-related trajectories between total and bioavailable testosterone are only partially explained by age changes in SHBG, whose levels increases at accelerated rates in old persons. Noteworthy, although mBT and cBT highly correlated with one another, mBT is a much stronger correlate of chronological age than cBT., Conclusion: In both men and women, mBT linearly declines over the life span and even at old ages. Its relationship with age-related phenotypes should be further investigated., (Published by Oxford University Press on behalf of the Gerontological Society of America 2016.)

Background: Emerging evidence suggests that mildly down-regulated thyroid function in older persons may protect and/or reflect maintained health., Methods: Using observational data collected between January 2006 and March 2014 on a volunteer sample of 602 men and women aged 68-97 years with normal thyroid function participating in the Baltimore Longitudinal Study of Aging, this study examines the concurrent relationship between reported walking ability, usual and rapid gait speed, endurance walk performance, fatigability, and reported energy level with respect to free thyroxine (FT4) within the normal range (0.76-1.50ng/dL) as a continuous variable and categorized as low (lower quartile), medium (interquartile), or high (upper quartile)., Results: Adjusting for sex, age, race, height, weight, exercise and smoking, reported walking ability, usual and rapid gait speed, 400-m time, fatigability, and reported energy level were less favorable with increasing FT4 (p = .013 to <.001). In sex-strata, similar associations were observed except for walking ability in men and energy level in women. Categorical analyses revealed that persons with low FT4 exhibited better functional mobility, fitness, and reported energy than persons with intermediate or high levels (p < .05 for all). Persons with high-normal versus medium FT4 had slower usual and rapid gait speed (p < .05) only., Conclusion: Older adults with low-normal FT4 exhibit better mobility, fitness, and fatigue profiles. Mildly down-regulated thyroid function appears to align with better function in old age and may serve as a biomarker of healthy longevity., (Published by Oxford University Press on behalf of the Gerontological Society of America 2016.)

Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved health across strains and sexes. Transcriptional and metabolomics changes driven by CR in liver indicated anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. CR prevented age-associated decline in the liver proteostasis network while increasing mitochondrial number, preserving mitochondrial ultrastructure and function with age. Abrogation of mitochondrial function negated life-prolonging effects of CR in yeast and worms. Our data illustrate the complexity of CR in the context of aging, with a clear separation of outcomes related to health and survival, highlighting complexities of translation of CR into human interventions., (Published by Elsevier Inc.)

Diabetes and impaired glucose tolerance affect a substantial proportion of older adults. Abnormal glucose metabolism is not a necessary component of aging. Older adults with diabetes and altered glucose status likely represent a subset of the population at high risk for complications and adverse geriatric syndromes. Goals for treatment of diabetes in the elderly include control of hyperglycemia, prevention and treatment of diabetic complications, avoidance of hypoglycemia, and preservation of quality of life. Research exploring associations of dysglycemia and insulin resistance with the development of adverse outcomes in the elderly may ultimately inform use of future glucose-lowering therapies in this population., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: To study the relationships between muscle mass, regional adiposity, and adipokines and glucose disposal in an older population., Design: Cross-sectional analysis., Setting: Community-dwelling volunteers from the Baltimore Longitudinal Study of Aging., Participants: Two hundred eighty men and 259 women with a mean age of 71.1 ± 0.4 (range 55-96) and complete data on fasting plasma adiponectin and leptin, oral glucose tolerance test (OGTT) (plasma glucose available at 0, 20, 40, 60, 80, 100, and 120 minutes), thigh computed tomography (CT), physical activity levels, and anthropometric measures., Measurements: Participants were classified into eight groups according to the presence of global adiposity (body mass index > 27 kg/m(2)), central adiposity (waist circumference > 88 cm for women and > 102 cm for men), and low muscle mass (CT thigh, lowest sex-specific tertile (93.8 cm(2) in women and 110.7 cm(2) in men) of adjusted thigh muscle area). Linear regression models were used to estimate the contribution of these eight groups to early glucose area under the curve (AUC) (t = 0-40 minutes), late glucose AUC (t = 60-120 minutes), and total glucose AUC (t = 0-120 minutes) from the OGTT., Results: Regardless of muscle mass, individuals with a combination of central and global adiposity were more likely to have delayed glucose disposal rates (P < .05). A strong negative association was also found between circulating adiponectin levels and glucose disposal rates (early AUC, β = -0.14; late AUC, β = -0.20; and total AUC, β = -0.20; P < .05 for all three AUCs) after adjusting for regional adiposity, muscle mass, circulating leptin levels, physical activity, age, and sex., Conclusion: Older individuals with global and central adiposity may be at risk of glucose intolerance unrelated to low muscle mass., (© 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.)

Ageing is associated with an increased incidence of hypertension, macrovascular disease and type 2 diabetes (non-insulin-dependent diabetes). It has been suggested that a common mechanism may be responsible for all of these pathological states since all of these conditions often cluster in the same individual. Epidemiological and clinical data have consistently demonstrated an association between insulin resistance and/or hyperinsulinaemia and glucose intolerance, dyslipidaemia and elevated systolic blood pressures. Therefore, insulin resistance and hyperinsulinaemia have been proposed as the causal link among the elements of the clusters. The elderly are more glucose intolerant and insulin resistant, but it remains controversial whether this decrease in function is due to an inevitable consequence of 'biological ageing' or due to environmental or lifestyle variables, noticeably increased adiposity/altered fat distribution and physical inactivity. An increase of these modifiable factors has been shown to result in increases in insulin resistance and hyperinsulinaemia and vice versa. However, insulin secretion appears to decrease with age even after adjustments for differences in adiposity, fat distribution and physical activity. The glucose intolerance of ageing may be due, in part, to decreased insulin sensitivity of pancreatic / cells to insulinotropic gut hormones (GLP1/GIP) and in part to alterations of hepatic glucose production.

The choroid plexus (CP) is an important cerebral structure involved in cerebrospinal fluid production and transport of solutes into the brain. Recent studies have uncovered the involvement of the CP in neurological disorders such as Alzheimer's disease and multiple sclerosis. However, our understanding of human age-related microstructural and functional changes in the CP with aging and neuropathology is limited. In this cross-sectional study, we investigated age and sex differences in the CP structure and function using advanced quantitative magnetic resonance imaging methodology in a large cohort (n = 155) of cognitively unimpaired individuals over a wide age range between 21 and 94 years. Our analysis included volumetric measurements, relaxometry measures (T 1 and T 2), diffusion tensor imaging (DTI) measures of fractional anisotropy (FA) and mean diffusivity (MD), as well as measures of cerebral blood flow (CBF). Our results revealed that CP volume was increasing with advancing age. We conjecture that this novel observation is likely attributed to alterations in the CP microstructure or function as well as to ventriculomegaly. Indeed, we also found that CBF was lower with advanced age, while, consistent with previous studies, T 1, T 2 and MD were higher, and FA was lower with advanced age. We attribute these functional and microstructural differences to a deteriorated CP structural integrity with aging. Furthermore, our relaxometry and DTI measures were found to be associated with differences in blood perfusion revealing lower microstructural integrity with lower CBF. Finally, in agreement with literature, sex-related differences in MD and CBF were statistically significant. This work lays the foundation for ongoing investigation of the involvement of CP in neurodegeneration. [ABSTRACT FROM AUTHOR]

Context Older adults have the greatest burden of diabetes; however, the contribution of age-related muscle loss to its development remains unclear. Objective We assessed the relationship of lean body mass with aging to incident diabetes in community-dwelling adults. Design and Setting We studied participants in the Baltimore Longitudinal Study of Aging with median follow-up of 7 years (range 1-16). Cox proportional hazard models with age as the time scale were used. Time-dependent lean body mass measures were updated at each follow-up visit available. Participants Participants included 871 men and 984 women without diabetes who had  ≥ 1 assessment of body composition using dual x-ray absorptiometry. Main Outcomes Incident diabetes, defined as self-reported history and use of glucose-lowering medications; or fasting plasma glucose ≥ 126 mg/dL and 2-hour oral glucose tolerance test glucose ≥ 200 mg/dL either at the same visit or 2 consecutive visits. Results The baseline mean [standard deviation] age was 58.9  [17.3] years. Men and women with a higher percentage of total lean body mass had lower fasting and 2-hour glucose levels, and less prediabetes (all P  < 0.01). Among men, comparing highest versus lowest quartiles, percentage of total lean body mass (hazard ratio [HR],  0.46; 95% confidence interval, 0.22-0.97), percentage leg lean mass (HR, 0.38; 0.15-0.96), and lean-to-fat mass ratio (HR, 0.39; 0.17-0.89) were inversely associated with incident diabetes after accounting for race and attenuated after adjustment for height and weight. Conversely, absolute total lean body mass was positively associated with incident diabetes among women, with similar trends in men. No associations were observed with muscle strength or quality. Conclusions Relatively lower lean body mass with aging is associated with incident diabetes in men and partially related to anthropometrics, but not so in women. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation has been linked to memory and other cognitive impairments, as well as Alzheimer's disease. Here, we investigate the association between inflammatory markers and changes in brain activity measured by regional cerebral blood flow (rCBF) to assess the relationship between inflammation and brain function in older individuals.Methods: Annual 15O water resting-state positron emission tomography (PET) scans collected over a 5-year period were assessed in 138 cognitively normal older participants (77 males; mean age at baseline = 71.3; mean scans per participant = 3.5) in the Baltimore Longitudinal Study of Aging. Voxel-wise linear mixed models were used to investigate associations between rCBF and C-reactive protein (CRP) and interleukin-6 (IL-6) at the time of scanning. We examined relationships between baseline CRP and IL-6 levels and baseline rCBF, and relationships between baseline and mean inflammatory levels over time and longitudinal rCBF changes.Results: Higher baseline CRP and IL-6 were each associated with lower baseline rCBF primarily in frontal and occipital regions, with only the lingual gyrus surviving atrophy correction. Higher baseline and mean CRP were also associated with greater rCBF declines over time in anterior cingulate and hippocampal regions, whereas higher baseline and mean IL-6 levels were associated with greater rCBF declines in orbitofrontal and hippocampal regions.Conclusions: Higher levels of inflammation are associated with longitudinal changes in brain function in regions important for cognition. These results, along with previous studies, suggest that chronic inflammation in older adults may contribute to age-associated declines in cognitive function. [ABSTRACT FROM AUTHOR]

Whether individuals with insulin resistance (IR) but without criteria for diabetes exhibit reduced mitochondrial oxidative capacity is unclear; addressing this question could guide research for new therapeutics. We investigated 248 participants without diabetes from the Baltimore Longitudinal Study of Aging (BLSA) to determine whether impaired mitochondrial capacity is associated with prediabetes, IR, and duration and severity of hyperglycemia exposure. Mitochondrial capacity was assessed as the postexercise phosphocreatine recovery time constant (τPCr) by 31P-magnetic resonance spectroscopy, with higher τPCr values reflecting reduced capacity. Prediabetes was defined using the American Diabetes Association criteria from fasting and 2-h glucose measurements. IR and sensitivity were calculated using HOMA-IR and Matsuda indices. The duration and severity of hyperglycemia exposure were estimated as the number of years from prediabetes onset and the average oral glucose tolerance test (OGTT) 2-h glucose measurement over previous BLSA visits. Covariates included age, sex, body composition, physical activity, and other confounders. Higher likelihood of prediabetes, higher HOMA-IR, and lower Matsuda index were associated with longer τPCr. Among 205 participants with previous OGTT data, greater severity and longer duration of hyperglycemia were independently associated with longer τPC In conclusion, in individuals without diabetes a more impaired mitochondrial capacity is associated with greater IR and a higher likelihood of prediabetes. [ABSTRACT FROM AUTHOR]

Normal aging is a complex process that affects every organ system in the body, including the taste system. Thus, we investigated the effects of the normal aging process on taste bud morphology, function, and taste responsivity in male mice at 2, 10, and 18 months of age. The 18-month-old animals demonstrated a significant reduction in taste bud size and number of taste cells per bud compared with the 2- and 10-month-old animals. The 18-month-old animals exhibited a significant reduction of protein gene product 9.5 and sonic hedgehog immunoreactivity (taste cell markers). The number of taste cells expressing the sweet taste receptor subunit, T1R3, and the sweet taste modulating hormone, glucagon-like peptide-1, were reduced in the 18-month-old mice. Concordant with taste cell alterations, the 18-month-old animals demonstrated reduced sweet taste responsivity compared with the younger animals and the other major taste modalities (salty, sour, and bitter) remained intact. [ABSTRACT FROM PUBLISHER]

Background: The current studies were designed to examine the effect of aging and diabetes on the enteroinsular axis.Methods: Healthy young control subjects (n = 10 young; age 23 +/- 1 years; body mass index [BMI] 24 +/- 1 kg/m(2)), healthy elderly subjects (n = 10; age 80 +/- 2 years; BMI 26 +/- 1 kg/m(2)), and elderly patients with type 2 diabetes (n = 10; age 76 +/- 2 years; BMI 26 +/- 2 kg/m(2)) underwent a 3-hour oral glucose tolerance test (glucose dose 40 gm/m(2)).Results: Insulin responses were not different between young controls and elderly patients with diabetes but were significantly lower in elderly patients with diabetes and young controls than in elderly controls (young control: 178 +/- 27 pM; elderly control: 355 +/- 57 pM; elderly diabetes: 177 +/- 30 pM; p <.05 elderly control vs young control and elderly diabetes). Total glucagon-like peptide 1 (GLP-1) responses were not significantly different between young and elderly controls and patients with diabetes (young control: 15 +/- 2 pM; old control: 8 +/- 2 pM; elderly diabetes: 12 +/- 3 pM; p = ns). Active GLP-1 responses were also not different between young and elderly controls and patients with diabetes (young control: 5 +/- 1 pM; old control: 6 +/- 1 pM; elderly diabetes: 7 +/- 1 pM; p = ns). However, the difference between total and active GLP levels was significantly greater in the young controls (young control: 10 +/- 2 pM; old control: 2 +/- 2 pM; elderly diabetes: 4 +/- 2 pM; p <.05, young vs elderly). Glucose-dependent insulinotropic polypeptide responses were not different between young and elderly controls and between elderly controls and patients with diabetes but were significantly higher in elderly patients with diabetes than in young controls (young control: 97 +/- 12 pM; elderly control: 121 +/- 16 pM; elderly diabetes: 173 +/- 27 pM; p <.05, young vs elderly diabetes). Glucagon responses were reduced in elderly controls but were similar in young controls and elderly patients with diabetes (young control: 15 +/- 1 pM; elderly control: 9 +/- 1 pM; elderly diabetes: 16 +/- 1 pM; p <.01 elderly control vs young control and elderly diabetes). Dipeptidyl peptidase IV levels were lower in both elderly controls and patients with diabetes when compared with young controls (young control: 0.17 +/- 0.01; elderly control: 0.15 +/- 0.01; elderly diabetes: 0.15 +/- 0.01 DeltaOD/20 minutes; p <.05, elderly vs young).Conclusions: We conclude that normal aging and diabetes are associated with multiple changes in the enteroinsular axis. [ABSTRACT FROM AUTHOR]

Epigenetic alterations are a key hallmark of aging but have been limitedly explored in tissues. Here, using naturally aged murine liver as a model and extending to other quiescent tissues, we find that aging is driven by temporal chromatin alterations that promote a refractory cellular state and compromise cellular identity. Using an integrated multi-omics approach and the first direct visualization of aged chromatin, we find that globally, old cells show H3K27me3-driven broad heterochromatinization and transcriptional suppression. At the local level, site-specific loss of H3K27me3 over promoters of genes encoding developmental transcription factors leads to expression of otherwise non-hepatocyte markers. Interestingly, liver regeneration reverses H3K27me3 patterns and rejuvenates multiple molecular and physiological aspects of the aged liver. [Display omitted] • Global increase of H3K27me3 is a common signature of aged liver and other tissues • H3K27me3 is lost at peak regions and gained at lamin-associated domains • Liver regeneration reverses age-related H3K27me3 and transcriptomic patterns Yang et al. find that the histone modification H3K27me3 accumulates in many tissues with age, due to increased time in quiescence. H3K27me3 is gained over lamin-associated domains but reduced at developmental gene promoters with consequent changes in global and local transcription. Liver regeneration breaks quiescence and partially restores youthful patterns. [ABSTRACT FROM AUTHOR]

Aims: Abdominal fat is a major determinant of metabolic diseases in older individuals. Obesity and diabetes are associated with low serum amylase (SA) levels, but the association between SA and metabolic disease is poorly understood. We investigated the association of low SA with diabetes and sex-specific associations of serum amylase with abdominal fat in older adults.Methods: In community-dwelling volunteers from the Baltimore Longitudinal Study of Aging (778 participants, age 66.8±13.6years), we assessed abdominal fat by computed tomography and diabetes status using the American Diabetes Association criteria. Linear regression analyses assessed the cross-sectional associations between abdominal fat and SA, and logistic regression assessed the odds of diabetes, given low SA.Results: In unadjusted analyses, individuals in the lowest SA quartile (<48μ/L) had 1.97 greater odds of diabetes, (95%CI, 1.01-3.83) than those in the highest quartile (⩾80μ/L). This association was no longer significant after adjusting for visceral adipose tissue area (VAT, dm(2)), abdominal subcutaneous adipose tissue (SAT, dm(2)) or BMI. In adjusted analyses, VAT and SAT were significantly associated with SA in both sexes. Among women, SA was more strongly associated with VAT than with SAT or BMI; VAT (β=-0.117±0.048, P<0.001), SAT (β=-0.023±0.025, P=0.346) and BMI (β=-0.0052±0.075, P=0.49).Conclusions: The association between SA and diabetes was explained mainly by abdominal visceral fat. In women, SA was more strongly associated with VAT than with BMI or SAT. These findings provide motivation for future mechanistic studies on SA's role in metabolic diseases. [ABSTRACT FROM AUTHOR]

Summary: Background: Evidence for a role of leptin in depression is limited and conflicting. Inconclusive findings may be explained by the complex effect of obesity on leptin signaling. In particular, both hyperleptinemia due to leptin resistance in obese persons as well as low leptin in lean persons can imply that low leptin biological signaling is associated with an increased risk of significant depressive symptoms. We tested whether the relationship between leptin and depressive symptoms is modulated by abdominal adiposity in two population-based studies. Methods: Data were from 851 participants (65–94 years) of the InCHIANTI Study and 1064 (26–93 years) of the Baltimore Longitudinal Study of Aging (BLSA). Plasma concentrations of leptin, waist circumference and depressive symptoms via the Center for Epidemiological Studies-Depression scale (CES-D) were assessed. In longitudinal InCHIANTI analyses onset of depressed mood (CES-D≥20) was evaluated over a 9-year follow-up. Results: In pooled cross-sectional analyses the interaction between leptin and waist circumference was significantly associated with CES-D scores ((log)leptin-by-waist interaction p =0.01). Also in longitudinal analyses, the (log)leptin-by-waist interaction term significantly (p =0.04) predicted depressed mood onset over time; depressed mood risk was especially increased for high levels of both leptin and waist circumference. Conclusions: The present findings suggest that low leptin signaling rather than low leptin concentration is a risk factor for depression. Future studies should develop proxy measures of leptin signaling by combining information on abdominal adiposity and leptin level to be used for clinical and research applications. [ABSTRACT FROM AUTHOR]