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There are no established or standardized definitions of aging-related disease. Data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 were used to model the relationship between age and incidence of diseases. Clustering analysis identified 4 groups of noncommunicable diseases: Group A diseases with an exponential increase in incidence with age; Group B diseases with an exponential increase in incidence that usually peaked in late life which then declined or plateaued at the oldest ages; and Groups C and D diseases with an onset in earlier life and where incidence was stable or decreased in old age. From an epidemiological perspective, Group A diseases are "aging-related diseases" because there is an exponential association between age and incidence, and the slope of the incidence curves remains positive throughout old age. These included the major noncommunicable diseases dementia, stroke, and ischemic heart disease. Whether any of the other diseases are aging-related is uncertain because their incidence either does not change or more often decreases in old age. Only biological studies can determine how the aging process contributes to any of these diseases and this may lead to a reclassification of disease on the basis of whether they are directly caused by or are in continuity with the biological changes of aging. In the absence of this mechanistic data, we propose the term "aging-related disease" should be used with precision based on epidemiological evidence. [ABSTRACT FROM AUTHOR]

Background: The association between dietary protein intake and the risk of mortality is still controversial. The present study aimed to examine the associations between dietary total, animal and plant protein intake and all‐cause and cause‐specific mortality. Methods: Community‐dwelling men aged ≥ 70 years were recruited from local government areas surrounding Concord Hospital in Sydney, New South Wales for the Concord Health and Ageing in Men Project (CHAMP). The research dietitian administered a standardised validated diet history questionnaire to capture baseline dietary intake. In total, 794 men participated in a detailed diet history interview at the third wave. Adequacy of protein intake was assessed by comparing participant intake with the Nutrient Reference Values. Total protein intake was categorised into quintiles. Sources of protein were also captured. Mortality was ascertained through the New South Wales death registry. Cox proportional hazard models were used to assess the association between dietary total, animal and plant protein intake and risk of mortality. Results: The mean age of the CHAMP men was 81 years. In total, 162 men died during a median follow‐up of 3.7 years. Of these, 54 (33.3%) and 49 (30.2%) men died due to cancer and cardiovascular disease, respectively. There were U‐shaped associations between protein intake and all‐cause and cancer mortality. In multiple adjusted analysis, the second (hazard ratio [HR] = 0.38; 95% confidence interval [CI] = 0.18–0.82) and third (HR = 0.36; 95% CI = 0.16–0.82) quintiles of protein intakes were significantly associated with reduced risk of all‐cause and only second quintile (HR = 0.47; 95% CI = 0.10–0.93) of protein intake was significantly associated with cancer mortality. Each serve increase in animal protein was significantly associated with 12% (HR = 1.12; 95% CI = 1.00–1.26) and 23% (HR = 1.23; 95% CI = 1.02–1.49) increased risk of all‐cause mortality and cancer mortality respectively. Conversely, each serve increase in plant protein intake was significantly associated with 25% (HR = 0.75; 95% CI 0.61–0.92) and 28% (HR = 0.72; 95% CI = 0.53–0.97) reduced risk of all‐cause and cancer mortality, respectively. No such associations were observed for cardiovascular disease mortality. Conclusions: Both second and third quintiles of total protein intake were associated with reduced all‐cause and cancer mortality. Plant protein was inversely associated with all‐cause and cancer mortality, whereas animal protein intake was positively associated with mortality. Key points: Our findings suggest a U‐shaped association between life expectancy and total protein intake, in which lifespan is greatest among people with 93–113 g day–1 total protein intake, a level that might be considered moderate in Australia but high in other countries.Both second and third quintiles of total protein intake (range between 79.23 and 107.19 g day–1) were associated with reduced risk of all‐cause and cancer mortality.Higher consumption of animal‐derived proteins was associated with greater mortality risk, whereas this association was reversed when protein consumption was replaced with plant‐derived protein. [ABSTRACT FROM AUTHOR]

Background: Nutritional intake could influence the development of frailty. The aim was to evaluate the associations between dietary iron intakes and changes in dietary iron intakes with frailty.Methods: Cross-sectional analyses involved 785 men with Fried frailty phenotype (FP) and 758 men with Rockwood frailty index (FI) data aged 75 years and older at nutrition assessment from the Concord Health and Ageing in Men Project prospective cohort study. Of these, 563 men who were FP robust or prefrail, and 432 men who were FI nonfrail were included in the longitudinal analyses for more than 3 years. Dietary intake was assessed at both timepoints using a validated diet history questionnaire. The dietary calculation was used to derive heme iron and nonheme iron intakes from total iron intakes. The associations were evaluated through binary logistic regression.Results: Incidence of FP frailty was 15.3% (n = 86). In longitudinal analyses, maintaining total iron intakes (medium tertile -2.61-0.81 mg/d), increases in total iron and nonheme iron intakes (high tertiles ≥0.82 mg/d and ≥0.80 mg/d), and changes in nonheme iron intake (1 mg increment) were associated with reduced risks of incident FP frailty (OR: 0.47 [95% confindence interval (CI): 0.24, 0.93, p = .031], OR 0.48 [95% CI: 0.23, 0.99, p = .048], OR 0.41 [95% CI: 0.20, 0.88, p = .022], and OR 0.89 [95% CI: 0.82, 0.98, p = .017]).Conclusion: Maintaining or increases in total dietary iron and increases or changes in dietary nonheme iron intakes more than 3 years were associated with reduced incidence of FP frailty in older men. [ABSTRACT FROM AUTHOR]

Aging and multimorbidity are associated with inflammation. Polypharmacy is common in older people with multimorbidity. Given the potential for interactions between polypharmacy and inflammation, the relationship between inflammation and polypharmacy were studied in older adults with multimorbidity and in healthy aging mice. A cross-sectional analysis of data from the 5-year wave of the Concord Health and Ageing in Men Project, a population-based study of community-dwelling men aged ≥70 years. Serum concentrations of 27 cytokines were measured using a multiplex immunoassay. Associations between polypharmacy (≥5 medications) and cytokines were evaluated using multivariable linear regression adjusting for age, frailty, comorbidities, and individual drug classes. Interaction between polypharmacy and Drug Burden Index (DBI-drugs with anticholinergic and sedative effects) was analyzed. Effects of polypharmacy and DBI on serum levels of 23 cytokines were determined in aging male mice treated with chronic polypharmacy or control. Compared to the nonpolypharmacy group (n = 495), CHAMP participants with polypharmacy (n = 409) had significantly higher concentrations of IL-8, IL-6, CCL3, Eotaxin, IL-1ra, IL-1β, IP-10, and lower concentrations of anti-inflammatory cytokine IL-4. In fully-adjusted multivariable models, polypharmacy was positively associated with concentrations of IL-8 and CCL3. There were no significant differences in inflammatory profiles between control and polypharmacy-treated mice. The relationship was not influenced by DBI in men or in mice. Inflammatory markers associated with polypharmacy in older adults were not seen in healthy aged mice administered polypharmacy, and may be related to underlying diseases. The polypharmacy mouse model provides opportunities for mechanistic investigations in translational research. [ABSTRACT FROM AUTHOR]

Aged care coverage in Australia is universal but fragmented and has been challenged by government policy to deregulate aged care and open it up to market forces. A recent inquiry into aged care (Royal Commission into Aged Care Quality and Safety) documented the outcome of this policy—substandard care at most levels. The provision of services to older Aboriginal and Torres Strait Islander peoples, who have high prevalence of frailty and cognitive impairment, was also identified as inadequate. The effects of yet to be implemented changes in policy and funding in response to this report remain to be seen. Despite this policy backdrop, geriatricians have contributed to a steady growth in medical services and interventions focussed on specific geriatric issues such as dementia, falls, polypharmacy and orthogeriatrics. These are often driven by, or in collaboration with researchers, and aim to generate research data as well as provide patient care. The numbers of academic geriatricians and other aged care health professionals is increasing, and the training of specialist geriatricians now includes a significant research component. [ABSTRACT FROM AUTHOR]

CR-night-fed mice outlived both CR-day groups: the CR-night-12 h and CR-night-2 h mice had median lifespans of 33.6% and 34.8% longer than the lifespan of AL mice. In the livers of mice with continuous access to food, aging promoted increases in inflammation and dysregulated metabolism, whereas a CR provided at night ameliorated most of these aging-related alterations. Keywords: Caloric restriction; Circadian rhythm; Longevity EN Caloric restriction Circadian rhythm Longevity e108 e110 3 03/24/23 20230101 NES 230101 Commentary on: 'Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice' by Victoria Acosta-Rodriguez I et al i . [Extracted from the article]

Males and females may respond differently to medications, yet knowledge about sexual dimorphisms in the effects of polypharmacy remains limited, particularly in aging. This study aimed to assess the effect of high Drug Burden Index (DBI) polypharmacy treatment compared to control on physical function and behavior in young and old, male and female mice. We studied whether age and sex play a role in physical function and behavior following polypharmacy treatment and whether they are paralleled by differences in serum drug levels. Young (2.5 months) and old (21.5 months), C57BL/6 mice were randomized to control or high DBI polypharmacy treatment (simvastatin, metoprolol, oxybutynin, oxycodone, and citalopram; n = 6-8/group) for 4-6 weeks. Compared to control, polypharmacy reduced physical function (grip strength, rotarod latency, gait speed, and total distance), middle zone distance (increased anxiety), and nesting score (reduced activities of daily living) in mice of both ages and sexes (p < .001). Old animals had a greater decline in nesting score (p < .05) and midzone distance (p < .001) than young animals. Grip strength declined more in males than females (p < .05). Drug levels at steady state were not significantly different between polypharmacy-treated animals of both ages and sexes. We observed polypharmacy-induced functional impairment in both age and sex groups, with age and sex interactions in the degree of impairment, which were not explained by serum drug levels. Studies of the pathogenesis of functional impairment from polypharmacy may improve management strategies in both sexes. [ABSTRACT FROM AUTHOR]

Background: Socioeconomic status (SES) has been suggested as a risk factor for falls but the few prospective studies to test this have had mixed results. We evaluated the prospective association between SES and falls in the Concord Health and Ageing in Men Project (CHAMP).Methods: CHAMP is a population-based prospective cohort study of men aged ≥70 years in Sydney, Australia. Incident falls were ascertained by triannual telephone calls for up to 4 years. SES was assessed with 4 indicators (education, occupation, source of income, home ownership) and cumulative SES score. We tested for interaction between SES indicators and country of birth and conducted stratified analyses.Results: We evaluated 1624 men (mean age: 77.3 ± 5.4 years). During a mean ± SD follow-up of 42.6 ± 8.7 months, 766 (47%) participants reported ≥1 incident falls. In nonstratified analyses, there were no associations between SES indicators and falls. In stratified analyses, falls rates were higher among Australian-born men with less formal education (incidence rate ratio [IRR] 1.66, 95% confidence interval [CI] 1.16-2.37, compared with those with more education) and those with low occupational position (1.45; 1.09-1.93). However, among men born in non-main English-speaking countries the rate of falls was lower among those with low educational level and no associations were evident for occupational position.Conclusions: Lower educational level and occupational position predicted a higher falls rate in Australian-born men; the opposite relationship was evident for educational level among migrants born in non-main English-speaking countries. Further studies should test these relationships in different populations and settings and evaluate targeted interventions. [ABSTRACT FROM AUTHOR]

Although characteristic changes in amino acid concentrations occur in obesity and sarcopenia, amino acids concentrations have not been reported in sarcopenic obesity. We studied n = 831 men aged 75 years and older from the 5-year follow-up of the Concord Health and Ageing in Men Project. Sarcopenia was defined using the Foundation of the National Institutes of Health criteria and obesity was defined as >30% fat mass. There were 31 men (3.7%) who had sarcopenic obesity. Branched chain amino acids were elevated in the obese (but not sarcopenic) group (n = 348) but reduced in both the sarcopenic (but not obese) (n = 44) and the sarcopenic obese groups. Apart from this, most of the amino acid concentrations were between those for the obese and the sarcopenic groups. Yet despite low concentrations of branched chain amino acids, the sarcopenic obese group had indications of insulin resistance and diabetes mellitus (fasting glucose and insulin concentrations, homeostatic model assessment, and percentage of participants taking diabetes medications) that were similar to the obese group. In summary, sarcopenic obese participants did not have a unique amino acid signature. In obesity, elevated branched chain amino acids are not a prerequisite for insulin resistance and diabetes if obesity is associated with sarcopenia. [ABSTRACT FROM AUTHOR]

Background Type 2 diabetes mellitus (T2DM) increases falls and fracture risk. Our objective was to compare incidence and risk factors for falls and fractures in community-dwelling older men with and without T2DM. Methods A total of 1705 men (471 with T2DM; 1234 without T2DM) aged ≥70 years were assessed at baseline. Men were contacted every 4 months for 6.0 ± 2.2 years to ascertain incident falls and fractures, with the latter being confirmed by radiographic reports. Hip fractures were ascertained via data linkage (follow-up: 8.8 ± 3.6 years). Risk factors for falls and fractures included physical activity and function, body composition, medications, and vision measures. Results Men with T2DM had similar fall (incident rate ratio [IRR]: 0.92 [95% confidence interval {CI}: 0.70, 1.12], n = 1246) and fracture rates (hazard ratio [HR]: 0.86 [95% CI: 0.56, 1.32], n = 1326) compared to men without T2DM after adjustment for significant risk factors. In men with T2DM, depression (IRR: 1.87 [95% CI: 1.05, 3.34], n = 333), sulphonylurea usage (IRR: 2.07 [95% CI: 1.30, 3.27]) and a greater number of prescription medications (IRR: 1.13 [95% CI: 1.03, 1.24]) were independently associated with increased fall rates, and higher total hip bone mineral density was independently associated with lower fracture rates (HR: 0.63 [95% CI: 0.47, 0.86], n = 351). Interaction terms demonstrated that better contrast sensitivity was independently associated with lower fracture rates (HR: 0.14 [95% CI: 0.02, 0.87]) in men with T2DM compared to men without T2DM. Conclusion Fall and fracture rates were similar in men with and without T2DM after adjusting for significant risk factors. Vision assessments including contrast sensitivity measures may improve fracture prediction in older men with T2DM. [ABSTRACT FROM AUTHOR]

Polypharmacy (use of ≥5 medications) and increasing Drug Burden Index (DBI) score (measure of person's total exposure to anticholinergic/sedative medications) are associated with impaired physical function in observational studies of older adults. Deprescribing, the supervised withdrawal of medications for which harms outweigh benefits for an individual, may be a useful intervention. Current knowledge is limited to clinical observational studies that are unable to determine causality. Here, we establish a preclinical model that investigates the effects of chronic polypharmacy, increasing DBI, and deprescribing on global health outcomes in aging. In a longitudinal study, middle-aged (12 months) male C57BL/6J (B6) mice were administered control feed or feed and/or water containing polypharmacy or monotherapy with different DBI scores. At 21 months, each treatment group was subdivided (stratified by frailty at 21 months) to either continue on treatment for life or to have treatment withdrawn (deprescribed). Frailty and physical function were evaluated at 12, 15, 18, and 24 months, and were analyzed using a mixed modeling approach. Polypharmacy with increasing DBI and monotherapy with citalopram caused mice to become frailer, less mobile, and impaired their strength and functional activities. Critically, deprescribing in old age reversed a number of these outcomes. This is the first preclinical study to demonstrate that chronic polypharmacy with increasing DBI augments frailty and impairs function in old age, and that drug withdrawal in old age reversed these outcomes. It was not the number of drugs (polypharmacy) but the type and dose of drugs (DBI) that caused adverse geriatric outcomes. [ABSTRACT FROM AUTHOR]

Carbohydrates are the major source of dietary energy, but their role in health and disease remains controversial. Recent epidemiological evidence suggests that the increased consumption of carbohydrates is associated with obesity and increased risk of mortality and dietary trials show that carbohydrate restriction leads to weight loss and improved glycaemic status in obese and diabetic subjects. In contrast, the diets of populations with long and healthy lifespans (e.g. traditional Okinawans from Japan) are high in carbohydrate and low in protein, and several clinical and preclinical studies have linked low-carbohydrate–high-protein diets with increased mortality risk. In this paper we attempt to reconcile these contradictory findings by moving beyond traditional single-nutrient analyses to consider the interactions between nutrients on health outcomes. We do so using the Geometric Framework (GF), a nutritional modelling platform that explicitly considers the main and interactive effects of multiple nutrients on phenotypic characteristics. Analysis of human data by GF shows that weight loss and improved cardio-metabolic outcomes under carbohydrate restriction derive at least in part from reduced caloric intake due to the concomitantly increased proportion of protein in the diet. This is because, as in many animals, a specific appetite for protein is a major driver of food intake in humans. Conversely, dilution of protein in the diet leverages excess food intake through compensatory feeding for protein ('protein leverage'). When protein is diluted in the diet by readily digestible carbohydrates and fats, as is the case in modern ultra-processed foods, protein leverage results in excess calorie intake, leading to rising levels of obesity and metabolic disease. However, when protein is diluted in the diet by increased quantities of less readily digestible forms of carbohydrate and fibre, energy balance is maintained and health benefits accrue, especially during middle age and early late-life. We argue that other controversies in carbohydrate research can be resolved using the GF methodology in dietary studies. [ABSTRACT FROM AUTHOR]

Increased blood levels of branched chain amino acids (BCAAs) have been associated with cardiometabolic risk factors. Here, we studied 918 community-dwelling older men to determine the relationship between BCAAs and other amino acids with cardiometabolic risk factors, major cardiovascular endpoints (MACE), and mortality. BCAAs had robust associations with many adverse metabolic risk factors (increased glucose, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), triglycerides; decreased high-density lipoprotein cholesterol). However, paradoxically, participants with lower levels of BCAAs had greater mortality and MACE possibly because increasing age and frailty, both of which were associated with lower BCAA levels, are powerful risk factors for these outcomes in older people. Overall, amino acids that were lowest in frail subjects (BCAAs, α-aminobutyric acid [AABA], histidine, lysine, methionine, threonine, tyrosine) were inversely associated with mortality and MACE. In conclusion, BCAAs are biomarkers for important outcomes in older people including cardiometabolic risk factors, frailty, and mortality. In old age, frailty becomes a dominant risk factor for MACE and mortality. [ABSTRACT FROM AUTHOR]

APOE genotype has been associated with various age-related outcomes including Alzheimer's disease, frailty, and mortality. In this study, the relationship between health, particularly cognitive function, and APOE was investigated in older men from the Concord Health and Ageing in Men Project (n = 1,616; age 76.9 ± 5.5 years [range 70-97 years]; Australia). Baseline characteristics and survival up to 12 years were determined. Frailty was measured using Cardiovascular Health study (CHS) criteria and Rockwood frailty index, and cognition using Mini-Mental State Examination (MMSE) and Addenbrookes Cognitive Examination. APOE ε4 was less common in the oldest men and those born in Mediterranean countries. APOE ε2 was beneficially associated with cholesterol, creatinine, gamma-glutamyl transaminase, glucose, and HDL cholesterol while APOE ε4 was adversely associated with cholesterol and albumin. APOE ε4 was associated with a clinical diagnosis of Alzheimer's disease when adjusted for age and region of birth (ε4 homozygotes Odds ratio (OR) 7.0; ε4 heterozygotes OR 2.4, p < .05), and APOE ε2 had a small positive association with cognition. On multivariate regression, overall cognitive function in the entire cohort was associated with age, country of birth, education, and frailty (all p < .001). APOE was not associated with frailty or survival. In conclusion, age and region of birth influenced distribution of APOE genotype in older men. Although APOE ε4 was associated with Alzheimer's disease, overall cognitive function in the cohort was associated more strongly with frailty than APOE genotype. [ABSTRACT FROM AUTHOR]

Aging is a powerful risk factor for the development of many chronic diseases including dementia. Research based on disease models of dementia have yet to yield effective treatments, therefore it is opportune to consider whether the aging process itself might be a potential therapeutic target for the treatment and prevention of dementia. Numerous cellular and molecular pathways have been implicated in the aging process and compounds that target these processes are being developed to slow aging and delay the onset of age-associated conditions. A few particularly promising therapeutic agents have been shown to influence many of the main hallmarks of aging and increase life span in rodents. Here we discuss the evidence that some of these antiaging compounds may beneficially affect brain aging and thereby lower the risk for dementia. [ABSTRACT FROM AUTHOR]

The management of frail older people is a key component of aged care. There has been a plethora of tools developed for the diagnosis and screening of frailty. Some of these tools are entering routine clinical practice at a time when the higher healthcare costs involved in caring for older people who are frail have become a potential target for cost-cutting. Yet there is still only limited evidence to support the widespread adoption of frailty tools, and foundational factors impact on their accuracy and validity. Despite the acceptance of frailty as a valid term in research and clinical practice, older people believe the term carries stigma. Such issues indicate that there may be a need to reconsider current approaches to frailty. Recent advances in the science of ageing biology can provide a new framework for reconfiguring how we screen, diagnose, treat and prevent frailty. Frailty can be considered to be a multisystem ageing syndrome of decreased physiological and functional reserve, where the biological changes of ageing are seen in most tissues and organs and are the pathogenic mechanism for frailty. Likewise age-related chronic disease and multimorbidity are syndromes where ageing changes occur in one or multiple systems, respectively. This model focusses diagnostic criteria for frailty onto the biomarkers of ageing and generates new targets for the prevention and treatment of frailty based on interventions that influence ageing biology. [ABSTRACT FROM AUTHOR]

Background: Weight loss increases fracture risk in older adults. We aimed to determine associations of 2-year body composition trajectories with subsequent falls and fractures in older men.Methods: We measured appendicular lean mass (ALM) and total fat mass (FM) by dual-energy X-ray absorptiometry at baseline and Year 2 in 1,326 community-dwelling men aged ≥70 and older. Body composition trajectories were determined from residuals of a linear regression of change in ALM on change in FM (higher values indicate maintenance of ALM over FM), and a categorical variable for change in ALM and FM (did not lose [≥-5% change] versus lost [<-5% change]). Bone mineral density (BMD), hand grip strength, and gait speed were assessed at Years 2 and 5. After Year 2, incident fractures (confirmed by radiographical reports) and falls were recorded for 6.8 years.Results: Compared with men who did not lose ALM or FM, men who did not lose ALM but lost FM, and men who lost both ALM and FM, had reduced falls (-24% and -34%, respectively; both p < .05). Men who lost ALM but did not lose FM had increased falls (incidence rate ratio = 1.73; 95% CI 1.37-2.18). ALM/FM change residuals were associated with improved lumbar spine BMD (B = 0.007; 95% CI 0.002-0.012 g/cm2 per SD increase) and gait speed (0.015; 0.001-0.029 m/s), and reduced hip fractures (hazard ratio = 0.68; 95% CI 0.47-0.99).Conclusions: Fracture risk may be increased in older men who lose higher ALM relative to FM. Weight loss interventions for obese older men should target maintenance of lean mass. [ABSTRACT FROM AUTHOR]

The authors discuss the new guidance to maintain the journal's commitment to inclusion, equity and diversity. Also cited are the promotion of concepts and works that aim to overcome inequality in health, social status, mental health and justice among older people, and the efforts to maintain a diverse author, reviewer and editorial cohorts in the journal to further nurture scholarships on aging.

Age-related changes in the liver sinusoidal endothelium, particularly the reduction in fenestrations, contribute to insulin resistance in old age. Metformin impacts on the aging process and improves insulin resistance. Therefore, the effects of metformin on the liver sinusoidal endothelium were studied. Metformin increased fenestrations in liver sinusoidal endothelial cells isolated from both young and old mice. Mice administered metformin in the diet for 12 months had increased fenestrations and this was associated with lower insulin levels. The effect of metformin on fenestrations was blocked by inhibitors of AMP-activated protein kinase (AMPK), endothelial nitric oxide synthase, and myosin light chain kinase phosphorylation. Metformin led to increased transgelin expression and structural changes in the actin cytoskeleton but had no effect on lactate production. Metformin also generated fenestration-like structures in SK-Hep1 cells, a liver endothelial cell line, and this was associated with increased ATP, cGMP, and mitochondrial activity. In conclusion, metformin ameliorates age-related changes in the liver sinusoidal endothelial cell via AMPK and endothelial nitric oxide pathways, which might promote insulin sensitivity in the liver, particularly in old age. [ABSTRACT FROM AUTHOR]

Background: The objective of the study is to evaluate the prospective associations between antioxidant intake and incident frailty among older Australian men aged ≥75 years.Methods: Seven hundred and ninety-four men participated in a detailed diet history interview at the Concord Health and Ageing in Men Project (CHAMP) study third wave (considered baseline nutrition here) and 781 men participated at the fourth wave (considered 3-year follow-up here). The main outcome measurement was incident frailty at 3-year follow-up, using the Cardiovascular Health Study definition. Dietary adequacy of antioxidant intake was assessed by comparing participants' median intakes of four dietary antioxidants (vitamin A, E, C, and zinc) to the nutrient reference values (NRVs). Attainment of the NRVs was incorporated into a dichotomized variable "poor" (meeting ≤2 antioxidants) or "good" (meeting ≥3 antioxidants) as the independent variable using the cut-point method. Also, intakes of each individual dietary antioxidant at baseline nutrition were categorized into quartiles. Analyses were performed using multinomial logistic regression.Results: Incidence of pre-frailty was 53.0% and frailty was 6.4% at 3-year follow-up. Poor dietary antioxidant intake (meeting ≤2) at baseline nutrition was associated with incident frailty at 3-year follow-up in unadjusted (OR: 2.59 [95% CI: 1.47, 4.59, p = .001]) and adjusted (OR: 2.46 [95% CI: 1.10, 5.51, p = .03]) analyses. The lowest quartile of vitamin E intake (<7.08 mg/d) was significantly associated with incident frailty (OR: 2.46 [95% CI: 1.01, 6.00, p = .05]).Conclusions: Poor antioxidant intake, particularly vitamin E, is a plausible factor associated with incident frailty among older men. This supports the need for clinical trials of diets rich in antioxidants or possibly low-dose antioxidant supplements, for prevention of frailty. [ABSTRACT FROM AUTHOR]

The liver endothelium plays a key role in the progression and resolution of liver diseases in young and adult individuals. However, its role in older people remains unknown. We have herein evaluated the importance of the sinusoidal endothelium in the pathophysiology of acute liver injury, and investigated the applicability of simvastatin, in aged animals. Eighteen-months-old male Wistar rats underwent 60 minutes of partial warm ischemia followed by 2 hours of reperfusion (WIR). A group of aged rats received simvastatin for 3 days before WIR. Endothelial phenotype, parenchymal injury, oxidative and nitrosative stress, and fenestrae dynamics were analyzed. The effects of WIR and simvastatin were investigated in primary LSEC from aged animals. The results of this study demonstrated that WIR significantly damages the liver endothelium and its effects are markedly worse in old animals. WIR-aged livers exhibited reduced vasodilation and sinusoidal capillarization, associated with liver damage and cellular stress. Simvastatin prevented the detrimental effects of WIR in aged livers. In conclusion, the liver sinusoidal endothelium of old animals is highly vulnerable to acute insult, thus targeted protection is especially relevant in preventing liver damage. Simvastatin represents a useful therapeutic strategy in aging. [ABSTRACT FROM AUTHOR]

The article presents a study which analyzed the effects of caregiving on death risks in older men, as well as in approving for caregiving-transition by individuals and adjusting for their health status changes over time. Also cited are the analysis on caregivers' mortality, the use of time-varying Cox proportional hazards model in examining risk of death in caregiving, as well as the Concord Health and Ageing in Men Projet (CHAMP) data.

Background: It is unclear whether older men with osteopenia/osteoporosis and sarcopenia (so-called osteosarcopenia) are at greater risk of falls and fractures than those with either condition alone.Methods: One thousand five hundred seventy-five community-dwelling men aged ≥70 years had appendicular lean mass, total hip and lumbar spine bone mineral density determined by dual-energy x-ray absorptiometry, and completed hand grip strength and gait speed tests. Osteopenia/osteoporosis was defined as a T-score at any site ≤-1.0 SD. Sarcopenia was defined using the European Working Group on Sarcopenia algorithm. Participants were contacted every 4 months for 6 ± 2 years to ascertain incident fractures (confirmed by radiographic reports) and for 2 years for incident falls.Results: Prevalence of osteosarcopenia was 8%, while 34% of participants had osteopenia/osteoporosis alone and 7% had sarcopenia alone. Men with osteosarcopenia had significantly increased fall (incidence rate ratio: 1.41; 95% confidence interval [CI]: 1.02 to 1.95) and fracture risk (hazard ratio: 1.87; 95% CI: 1.07 to 3.26) compared with men with neither osteopenia/osteoporosis nor sarcopenia. There was no statistical interaction between osteopenia/osteoporosis and sarcopenia, and falls and fracture risk were not different for osteosarcopenia compared with either condition alone (all p > .05).Conclusions: Community-dwelling older men with combined osteopenia/osteoporosis and sarcopenia do not have increased falls and fracture risk compared with those with either condition. Further research is required to clarify whether the term "osteosarcopenia" has any meaning above and beyond either term alone and therefore potential clinical utility for falls and fracture prediction. [ABSTRACT FROM AUTHOR]

Background: Previous studies demonstrated associations between IL-6 and frailty, but associations between a wide range of cytokines, chemokines, and growth factors with prevalent and incident frailty has not been studied.Methods: Community-dwelling men aged more than 75 enrolled in the 5-year and 8-year follow-up of the CHAMP study were assessed. Twenty-seven inflammatory biomarkers were measured using the Bio-Plex Pro Human Cytokine 27-plex Assay kit at 5-year follow-up. Frailty was determined using the Fried frailty phenotype (FP) and Rockwood frailty index (FI) at both time-points. Age, body mass index, smoking, alcohol, and comorbidity were also assessed.Results: In cross-sectional analysis of the 5-year follow-up, the unadjusted odds ratio (OR) for frail versus robust evaluated by the FP showed significant associations for IL-6 (OR: 1.56, 95% confidence interval [CI]: 1.23-1.98) and IL-8 (OR: 1.28, 95% CI: 1.00-1.63). IL-6 remained significantly associated in the age-adjusted (OR: 1.58, 95% CI: 1.21-2.05) and multivariable-adjusted model (OR: 1.54, 95% CI: 1.16-2.05). No associations were observed between pre-frail versus robust. In longitudinal unadjusted analysis, IL-8 (OR: 1.32, 95% CI: 1.03-1.70) and IP-10 (OR: 1.32, 95% CI: 1.03-1.70) at 5-year predicted incident frailty at 8-year follow-up. IL-8 remained longitudinally associated with incident frailty after age (OR: 1.34, 95% CI: 1.03-1.75) but not multivariable (OR: 1.20, 95% CI: 0.98-1.70) adjustment. Similar results were seen using the FI. None of the other biomarkers had significant associations with incident frailty.Conclusions: Our findings suggest that IL-6 and IL-8 may be cross-sectionally associated with frailty and that all measured inflammatory biomarkers were not causally related to frailty. Together with previous studies, the results suggest that frailty is specifically linked to IL-6 and IL-8 rather than simply representing a nonspecific pan-inflammatory condition. [ABSTRACT FROM AUTHOR]

Background previous cross-sectional studies have reported bidirectional associations between sexual activity and cognitive function among older people. However, the temporal associations have not been studied. Methods community-dwelling men aged 70+ from the Concord Health and Ageing in Men Project were assessed. This study was based on 986 men at baseline, 829 men at 2 year and 595 men at 5-year follow-up. Sexual function using a standardised questionnaire (erectile function, sexual activity, sexual satisfaction, sexual desire) was analysed by generalised estimating equations to examine associations between changes in sexual function and changes in mini-mental state examination (MMSE) across three time points over 5 years. Age, BMI, comorbidity, self-rated health, smoking, number of medications, country of birth, education, marital status, depression and reproductive hormones were also measured at all time points. Results in unadjusted models, declines in erectile function (β = −0.317) and sexual activity (β = −0.575) over time were statistically significantly associated with a decline in MMSE over time. The associations observed in the unadjusted models remained after adjusting for a range of covariables. Declines in sexual satisfaction and sexual desire over time were not associated with changes in MMSE. Conclusions our findings provide evidence of a longitudinal temporal relationship between sexual activity and cognitive function. Further studies are warranted to examine whether maintaining a healthy sexual life has a positive effect on cognitive function in older men. [ABSTRACT FROM AUTHOR]

The article focuses on the caloric restriction (CR) effects on aging. Topics include aging is the leading risk factor for chronic diseases and disability, and CR appears to have broad-spectrum effectiveness, delaying the onset of a range of age-related conditions; mentions the effect of retarding growth upon the total length of life and to measure the effects of retarded growth upon the size of the animal's body; and also mentions CR improved health span without an increase in lifespan.

Although most self-reactive T cells are eliminated in the thymus, mechanisms to inactivate or control T cells specific for extrathymic antigens are required and exist in the periphery. By investigating the site in which autoreactive T cells are tolerized, we identify a unique mechanism of peripheral deletion in which naïve autoreactive CD8 T cells are rapidly eliminated in the liver after intrahepatic activation. T cells actively invade hepatocytes, enter endosomal/lysosomal compartments, and are degraded. Blockade of this process leads to accumulation of autoreactive CD8 T cells in the liver and breach of tolerance, with the development of autoimmune hepatitis. Cell into cell invasion, or emperipolesis, is a long-observed phenomenon for which a physiological role has not been previously demonstrated. We propose that this "suicidal emperipolesis" is a unique mechanism of autoreactive T-cell deletion, a process critical for the maintenance of tolerance. [ABSTRACT FROM AUTHOR]

Serum uric acid (UA) is a strong endogenous antioxidant. Since oxidative stress has been linked to osteoporosis, we examined the association between serum UA levels and bone mineral density (BMD), prevalent vertebral and nonvertebral fractures, and laboratory measures such as calcitropic hormones and bone turnover marker levels. This cross-sectional analysis consisted of 1705 community-dwelling men aged 70 years or over who participated in the baseline part of the Concord Health and Ageing in Men Project (CHAMP), a population-based study of older men in Sydney, Australia. BMD at all sites was significantly higher among men with serum UA levels above the group median than among men with UA levels below the median. In multiple regression analyses adjusted for potential confounders, serum UA remained associated with BMD at all sites (β = 0.12 to 0.14, p < .001), serum calcium (β = 0.11, p = .001), parathyroid hormone (β = 0.09, p = .002), 25-hydroxyvitamin D (β = 0.09, p = .005), and was negatively associated with urinary excretion amino-terminal cross-linked telopeptide of type 1 collagen (β = -0.09, p = .006). Overall, serum UA accounted for 1.0% to 1.44% of the variances in BMD ( R = 0.10 to 0.22). In multiple logistic regression analyses, above-median serum UA levels were associated with a lower prevalence of osteoporosis at the femoral neck [odds ratio (OR) = 0.42, 95% confidence interval (CI) 0.22-0.81, p = .010) and lumbar spine (OR = 0.44, 95% CI 0.23-0.86, p = .016) and a lower prevalence of vertebral (OR = 0.62, 95% CI 0.43-0.91, p = .015) and nonvertebral (OR = 0.51, 95% CI 0.29-0.89, p = .018) fractures. In conclusion, higher serum UA levels are associated with higher BMD at all skeletal sites and with a lower prevalence of vertebral and nonvertebral fractures in older men. © 2011 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Aging is associated with marked changes in the hepatic sinusoid, yet the effect of old age on hepatic stellate cells (HSC) has not been well described. Transmission electron microscopy and immunohistochemistry were used to study the effects of aging on HSC in livers from rats (3-4 mths versus 24-27 mths) and mice (2-3 mths versus 20-22 mths). Desmin-positive HSC doubled in old age in both mice and rats. Alpha-smooth muscle actin- (αSMA-) positive cells did not increase significantly and remained only a small percentage of desmin-positive cells. Electron microscopy revealed that old age is associated with HSC that have a substantial increase in the number of lipid droplets which are larger in diameter. There was also a marked increase of HSC that protruded into the sinusoidal lumen in old mice. In conclusion, old age is associated with hyperplasia of HSC that are not activated and are engorged with lipid droplets. [ABSTRACT FROM AUTHOR]