Human beings have been recently reviewed as ‘metaorganisms’ as a result of a close symbiotic relationship with the intestinal microbiota. This assumption imposes a more holistic view of the ageing process where dynamics of the interaction between environment, intestinal microbiota and host must be taken into consideration. Age-related physiological changes in the gastrointestinal tract, as well as modification in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbial ecosystem. Here we review the current knowledge of the changes occurring in the gut microbiota of old people, especially in the light of the most recent applications of the modern molecular characterisation techniques. The hypothetical involvement of the age-related gut microbiota unbalances in the inflamm-aging, and immunosenescence processes will also be discussed. Increasing evidence of the importance of the gut microbiota homeostasis for the host health has led to the consideration of medical/nutritional applications of this knowledge through the development of probiotic and prebiotic preparations specific for the aged population. The results of the few intervention trials reporting the use of pro/prebiotics in clinical conditions typical of the elderly will be critically reviewed.
Resveratrol is a polyphenol that is mainly found in grapes and red wine and has been reported to be a caloric restriction (CR) mimetic driven by Sirtuin 1 (SIRT1) activation. Resveratrol increases metabolic rate, insulin sensitivity, mitochondrial biogenesis and physical endurance, and reduces fat accumulation in mice. In addition, resveratrol may be a powerful agent to prevent age-associated neurodegeneration and to improve cognitive deficits in Alzheimer's disease (AD). Moreover, different findings support the view that longevity in mice could be promoted by CR. In this study, we examined the role of dietary resveratrol in SAMP8 mice, a model of age-related AD. We found that resveratrol supplements increased mean life expectancy and maximal life span in SAMP8 and in their control, the related strain SAMR1. In addition, we examined the resveratrol-mediated neuroprotective effects on several specific hallmarks of AD. We found that long-term dietary resveratrol activates AMPK pathways and pro-survival routes such as SIRT1 in vivo. It also reduces cognitive impairment and has a neuroprotective role, decreasing the amyloid burden and reducing tau hyperphosphorylation.
The role of epigenetics in the modulation of longevity has not been studied in humans. To this aim, (1) we evaluated the DNA methylation from peripheral leukocytes of 21 female centenarians, their 21 female offspring, 21 offspring of both non-long-lived parents, and 21 young women through ELISA assay, pyrosequencing analysis of Alu sequences, and quantification of methylation in CpG repeats outside CpG islands; (2) we compared the DNA methylation profiles of these populations through Infinium array for genome-wide CpG methylation analysis. We observed an age-related decrease in global DNA methylation and a delay of this process in centenarians’ offspring. Interestingly, literature data suggest a link between the loss of DNA methylation observed during aging and the development of age-associated diseases. Genome-wide methylation analysis evidenced DNA methylation profiles specific for aging and longevity: (1) aging-associated DNA hypermethylation occurs predominantly in genes involved in the development of anatomical structures, organs, and multicellular organisms and in the regulation of transcription; (2) genes involved in nucleotide biosynthesis, metabolism, and control of signal transmission are differently methylated between centenarians’ offspring and offspring of both non-long-lived parents, hypothesizing a role for these genes in human longevity. Our results suggest that a better preservation of DNA methylation status, a slower cell growing/metabolism, and a better control in signal transmission through epigenetic mechanisms may be involved in the process of human longevity. These data fit well with the observations related to the beneficial effects of mild hypothyroidism and insulin-like growth factor I system impairment on the modulation of human lifespan.
Immunosenescence is the term commonly used to describe the multifaceted phenomenon encompassing all changes occurring in the immune system during aging. It contributes to render older adults more prone to develop infectious disease and main age-related diseases. While age clearly imposes drastic changes in immune physiology, older adults have heterogeneous health and immune phenotypes. This confronts scientists and researcher to develop more age-specific interventions rather than simply adopting intervention regimes used in younger people and this in order to maintain immune protection in older adults. Thus, this review provides evidences of the central role played by cell-mediated immunity in the immunosenescence process and explores the means by which senescent state of the cell-mediated immune function could be identified and predicted using biomarkers. Furthermore considerations are given to recent advances made in the field of age-specific immune interventions that could contribute to maintain immune protection, to improve quality of life, and/or to promote healthy aging of the growing part of the population.
This randomized controlled trial examined the effects of multicomponent training on muscle power output, muscle mass, and muscle tissue attenuation; the risk of falls; and functional outcomes in frail nonagenarians. Twenty-four elderly (91.9 ± 4.1 years old) were randomized into intervention or control group. The intervention group performed a twice-weekly, 12-week multicomponent exercise program composed of muscle power training (8–10 repetitions, 40–60 % of the one-repetition maximum) combined with balance and gait retraining. Strength and power tests were performed on the upper and lower limbs. Gait velocity was assessed using the 5-m habitual gait and the time-up-and-go (TUG) tests with and without dual-task performance. Balance was assessed using the FICSIT-4 tests. The ability to rise from a chair test was assessed, and data on the incidence and risk of falls were assessed using questionnaires. Functional status was assessed before measurements with the Barthel Index. Midthigh lower extremity muscle mass and muscle fat infiltration were assessed using computed tomography. The intervention group showed significantly improved TUG with single and dual tasks, rise from a chair and balance performance (P < 0.01), and a reduced incidence of falls. In addition, the intervention group showed enhanced muscle power and strength (P < 0.01). Moreover, there were significant increases in the total and high-density muscle cross-sectional area in the intervention group. The control group significantly reduced strength and functional outcomes. Routine multicomponent exercise intervention should be prescribed to nonagenarians because overall physical outcomes are improved in this population.
In order to identify new markers of vascular cell senescence with potential in vivo implications, primary cultured endothelial cells, including human umbilical vein endothelial cells (HUVECs), human aortic endothelial cells (HAECs), human coronary artery endothelial cells (HCAECs) and ex vivo circulating angiogenic cells (CACs), were analysed for microRNA (miR) expression. Among the 367 profiled miRs in HUVECs, miR-146a, miR-9, miR-204 and miR-367 showed the highest up-regulation in senescent cells. Their predicted target genes belong to nine common pathways, including Toll-like receptor signalling (TLR) that plays a pivotal role in inflammatory response, a key feature of senescence (inflammaging). MiR-146a was the most up-regulated miR in the validation analysis (>10-fold). Mimic and antagomir transfection confirmed TLR’s IL-1 receptor-associated kinase (IRAK1) protein modulation in both young and senescent cells. Significant correlations were observed among miR-146a expression and β-galactosidase expression, telomere length and telomerase activity. MiR-146a hyper-expression was also validated in senescent HAECs (>4-fold) and HCAECs (>30-fold). We recently showed that CACs from patients with chronic heart failure (CHF) presented a distinguishing feature of senescence. Therefore, we also included miR-146a expression determination in CACs from 37 CHF patients and 35 healthy control subjects (CTR) for this study. Interestingly, a 1,000-fold increased expression of miR-146a was observed in CACs of CHF patients compared to CTR, along with decreased expression of IRAK1 protein. Moreover, significant correlations among miR-146a expression, telomere length and telomerase activity were observed. Overall, our findings indicate that miR-146a is a marker of a senescence-associated pro-inflammatory status in vascular remodelling cells.
Changes in satellite cell content play a key role in regulating skeletal muscle growth and atrophy. Yet, there is little information on changes in satellite cell content from birth to old age in humans. The present study defines muscle fiber type-specific satellite cell content in human skeletal muscle tissue over the entire lifespan. Muscle biopsies were collected in 165 subjects, from different muscles of children undergoing surgery (<18 years; n = 13) and from the vastus lateralis muscle of young adult (18–49 years; n = 50), older (50–69 years; n = 53), and senescent subjects (70–86 years; n = 49). In a subgroup of 51 aged subjects (71 ± 6 years), additional biopsies were collected after 12 weeks of supervised resistance-type exercise training. Immunohistochemistry was applied to assess skeletal muscle fiber type-specific composition, size, and satellite cell content. From birth to adulthood, muscle fiber size increased tremendously with no major changes in muscle fiber satellite cell content, and no differences between type I and II muscle fibers. In contrast to type I muscle fibers, type II muscle fiber size was substantially smaller with increasing age in adults (r = −0.56; P < 0.001). This was accompanied by an age-related reduction in type II muscle fiber satellite cell content (r = −0.57; P < 0.001). Twelve weeks of resistance-type exercise training significantly increased type II muscle fiber size and satellite cell content. We conclude that type II muscle fiber atrophy with aging is accompanied by a specific decline in type II muscle fiber satellite cell content. Resistance-type exercise training represents an effective strategy to increase satellite cell content and reverse type II muscle fiber atrophy.
Sarcopenia, low muscle mass, is an increasing problem in our ageing society. The prevalence of sarcopenia varies extremely between elderly cohorts ranging from 7% to over 50%. Without consensus on the definition of sarcopenia, a variety of diagnostic criteria are being used. We assessed the degree of agreement between seven different diagnostic criteria for sarcopenia based on muscle mass and handgrip strength, described in literature. In this cross-sectional study, we included men (n = 325) and women (n = 329) with complete measurements of handgrip strength and body composition values as measured by bioimpedance analysis within the Leiden Longevity Study. Prevalence of sarcopenia was stratified by gender and age. In men (mean age 64.5 years), the prevalence of sarcopenia with the different diagnostic criteria ranged from 0% to 20.8% in the lowest age category (below 60 years), from 0% to 31.2% in the middle (60 to 69 years) and from 0% to 45.2% in the highest age category (above 70 years). In women (mean age 61.8 years), the prevalence of sarcopenia ranged from 0% to 15.6%, 0% to 21.8% and 0% to 25.8% in the lowest, middle and highest age category, respectively. Only one participant (0.2%) was identified having sarcopenia according to all diagnostic criteria that marked prevalence above 0%. We conclude that the prevalence of sarcopenia is highly dependent on the applied diagnostic criteria. It is necessary to reach a consensus on the definition of sarcopenia in order to make studies comparable and for implementation in clinical care.
The increase of elderly in our society requires simple tools for quantification of sarcopenia in inpatient and outpatient settings. The aim of this study was to compare parameters determined with musculoskeletal ultrasound (M-US) with muscle strength in young and elderly patients. In this prospective, randomised and observer blind study, 26 young (24.2 ± 3.7 years) and 26 old (age 67.8 ± 4.8 years) patients were included. Muscle thickness, pennation angle and echogenicity of all muscles of musculus quadriceps were measured by M-US and correlated with isometric maximum voluntary contraction force (MVC) of musculus quadriceps. Reproducibility of M-US measurements as well as simple and multiple regression models were calculated. Of all measured M-US variables the highest reproducibility was found for measurements of thickness (intraclass correlation coefficients, 85–97 %). Simple regression analysis showed a highly significant correlation of thickness measurements of all muscles of musculus quadriceps with MVC in the elderly and in the young. Multiple regression analysis revealed that thickness of musculus vastus medialis had the best correlation with MVC in the elderly. This study showed that measurement of muscle thickness, especially of musculus vastus medialis, by M-US is a reliable, bedside method for monitoring the extent of sarcopenia.
Aging is an important factor in memory decline in aged animals and humans and in Alzheimer’s disease and is associated with the impairment of hippocampal long-term potentiation (LTP) and down-regulation of NR1/NR2B expression. Gaseous formaldehyde exposure is known to induce animal memory loss and human cognitive decline; however, it is unclear whether the concentrations of endogenous formaldehyde are elevated in the hippocampus and how excess formaldehyde affects LTP and memory formation during the aging process. In the present study, we report that hippocampal formaldehyde accumulated in memory-deteriorating diseases such as age-related dementia. Spatial memory performance was gradually impaired in normal Sprague–Dawley rats by persistent intraperitoneal injection with formaldehyde. Furthermore, excess formaldehyde treatment suppressed the hippocampal LTP formation by blocking N-methyl-d-aspartate (NMDA) receptor. Chronic excess formaldehyde treatment over a period of 30 days markedly decreased the viability of the hippocampus and down-regulated the expression of the NR1 and NR2B subunits of the NMDA receptor. Our results indicate that excess endogenous formaldehyde is a critical factor in memory loss in age-related memory-deteriorating diseases.
In the last decades, the participation of elderly trained people in endurance events such as marathon running has dramatically increased. Previous studies suggested that the performance of master runners (>40 years) during marathon running has improved. The aims of the study were (1) to analyze the changes in participation and performance trends of master marathon runners between 1980 and 2009, and (2) to compare the gender differences in performance as a function of age across the years. Running times of the best male and female runners between 20 and 79 years of age who competed in the New York City Marathon were analyzed. Gender differences in performance times were analyzed for the top 10 male and female runners between 20 and 65 years of age. The participation of master runners increased during the 1980–2009 period, to a greater extent for females compared to males. During that period, running times of master runners significantly (P < 0.01) decreased for males older than 64 years and for females older than 44 years, respectively. Gender differences in running times decreased over the last three decades but remained relatively stable across the ages during the last decade. These data suggest that male (≥65 years) and female (≥45 years) master runners have probably not yet reached their limits in marathon performance. The relative stability of gender differences in marathon running times across the different age groups over the last decade also suggests that age-related declines in physiological function do not differ between male and female marathoners.
MicroRNAs (miRs) are small non- coding RNA molecules controlling a plethora of biological processes such as development, cellular survival and senescence. We here determined miRs differentially regulated during cardiac postnatal development and aging. Cardiac function, morphology and miR expression profiles were determined in neonatal, 4 weeks, 6 months and 19 months old normotensive male healthy C57/Bl6N mice. MiR-22 was most prominently upregulated during cardiac aging. Cardiac expression of its bioinformatically predicted target mimecan (osteoglycin, OGN) was gradually decreased with advanced age. Luciferase reporter assays validated mimecan as a bona fide miR-22 target. Both, miR-22 and its target mimecan were co- expressed in cardiac fibroblasts and smooth muscle cells. Functionally, miR-22 overexpression induced cellular senescence and promoted migratory activity of cardiac fibroblasts. Small interference RNA-mediated silencing of mimecan in cardiac fibroblasts mimicked the miR-22-mediated effects. Rescue experiments revealed that the effects of miR-22 on cardiac fibroblasts were only partially mediated by mimecan. In conclusion, miR-22 upregulation in the aging heart contributed at least partly to accelerated cardiac fibroblast senescence and increased migratory activity. Our results suggest an involvement of miR-22 in age-associated cardiac changes, such as cardiac fibrosis.
Aging is a progressive process that results in the accumulation of intra- and extracellular alterations that in turn contribute to a reduction in health. Age-related changes in DNA methylation have been reported before and may be responsible for aging-induced changes in gene expression, although a causal relationship has yet to be shown. Using genome-wide assays, we analyzed age-induced changes in DNA methylation and their effect on gene expression with and without transient induction with the synthetic transcription modulating agent WY14,643. To demonstrate feasibility of the approach, we isolated peripheral blood mononucleated cells (PBMCs) from five young and five old healthy male volunteers and cultured them with or without WY14,643. Infinium 450K BeadChip and Affymetrix Human Gene 1.1 ST expression array analysis revealed significant differential methylation of at least 5 % (¿YO¿>¿5 %) at 10,625 CpG sites between young and old subjects, but only a subset of the associated genes were also differentially expressed. Age-related differential methylation of previously reported epigenetic biomarkers of aging including ELOVL2, FHL2, PENK, and KLF14 was confirmed in our study, but these genes did not display an age-related change in gene expression in PBMCs. Bioinformatic analysis revealed that differentially methylated genes that lack an age-related expression change predominantly represent genes involved in carcinogenesis and developmental processes, and expression of most of these genes were silenced in PBMCs. No changes in DNA methylation were found in genes displaying transiently induced changes in gene expression. In conclusion, aging-induced differential methylation often targets developmental genes and occurs mostly without change in gene expression.
This study investigated the effects of a multicomponent exercise intervention on muscle strength, incidence of falls and functional outcomes in frail elderly patients with dementia after long-term physical restraint, followed by 24 weeks of training cessation. Eighteen frail elderly patients with mild dementia (88.1 ± 5.1 years) performed a multicomponent exercise program, which consisted of 4 weeks of walking, balance and cognitive exercises, followed by 4 weeks of resistance exercise performed twice weekly [8–12 repetitions at 20–50 % of the one-repetition maximum (1RM)], combined with walking, balance and cognitive exercises. Before and after training, as well as after 24 weeks of training cessation, strength outcomes, Barthel Index, balance, gait ability, rise from a chair ability, dual task performance, incidence of falls and Mini-Mental State Examination were assessed. After the first 4 weeks of training, there was a significant improvement only in the balance test, whereas no additional changes were observed. However, after the second part of the training, the participants required significantly less time for the time-up-and-go test (P < 0.05), and improved the isometric hand grip, hip flexion and knee extension strength, as well as the leg press 1RM (P < 0.01). A significant reduction was also observed in the incidence of falls (P < 0.01). After 24 weeks of training cessation, abrupt decreases were observed in nearly all of the physical outcomes (P < 0.05). The exercise intervention improved strength, balance and gait ability in frail elderly patients with dementia after long-term physical restraint, and these benefits were lost after training cessation.
Oxidative stress from generation of increased reactive oxygen species or free radicals of oxygen has been reported to play an important role in the aging. To investigate the relationship between the oxidative stress and memory decline during aging, we have determined the level of lipid peroxidation, activities of antioxidant enzymes, and activity of acetylcholine esterase (AChE) in brain and plasma as well as biogenic amine levels in brain from Albino–Wistar rats at age of 4 and 24 months. The results showed that the level of lipid peroxidation in the brain and plasma was significantly higher in older than that in the young rats. The activities of antioxidant enzymes displayed an age-dependent decline in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly decreased in brain and plasma of aged rats. Superoxide dismutase (SOD) was also significantly decreased in plasma of aged rats; however, a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in aged rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM) and Elevated plus Maze (EPM) test. Short-term memory and long-term memory was impaired significantly in older rats, which was evident by a significant increase in the latency time in MWM and increase in transfer latency in EPM. Moreover, a marked decrease in biogenic amines (NA, DA, and 5-HT) was also found in the brain of aged rats. In conclusion, our data suggest that increased oxidative stress, decline of antioxidant enzyme activities, altered AChE activity, and decreased biogenic amines level in the brain of aged rats may potentially be involved in diminished memory function.
Dual tasks that involve walking and cognitive interference tests are commonly used in mobility assessments and interventions. However, factors that explain variance in dual-task performance costs are poorly understood. We, therefore, examined the moderating effects of two putative constructs, postural reserve and hazard estimate, on performance on a walking while talking paradigm. Participants were 285 non-demented older adults (mean age = 76.9 years; %female = 54.4). Postural reserve was operationalized as the presence or absence of clinical gait abnormalities. An empirical factor, based on measures of executive functions, served as a marker for hazard estimate. The moderation effects of postural reserve and hazard estimate on dual-task costs were examined via two-way interactions in a joint linear mixed effect model. Significant dual-task costs were observed for gait speed (95% CI = 30.814 to 39.121) and cognitive accuracy (95% CI = 6.568 to 13.607). High hazard estimate had a protective effect against decline in gait speed (95% CI = −8.372 to −0.151) and cognitive accuracy (95% CI = −8.372 to −0.680). Poor postural reserve was associated with reduced decline in gait speed (95% CI = −9.611 to −0.702) but did not moderate the decline in cognitive accuracy (95% CI = −3.016 to 4.559). Assessing postural reserve and hazard estimate can help improve mobility risk assessment procedures and interventions for individuals with cognitive and movement disorders.
Increased vascular stiffness, endothelial dysfunction, and isolated systolic hypertension are hallmarks of vascular aging. Regular cocoa flavanol (CF) intake can improve vascular function in healthy young and elderly at-risk individuals. However, the mechanisms underlying CF bioactivity remain largely unknown. We investigated the effects of CF intake on cardiovascular function in healthy young and elderly individuals without history, signs, or symptoms of cardiovascular disease by applying particular focus on functional endpoints relevant to cardiovascular aging. In a randomized, controlled, double-masked, parallel-group dietary intervention trial, 22 young (<35 years) and 20 elderly (50–80 year) healthy, male non-smokers consumed either a CF-containing drink (450 mg CF) or nutrient-matched, CF-free control drink bi-daily for 14 days. The primary endpoint was endothelial function as measured by flow-mediated vasodilation (FMD). Secondary endpoints included cardiac output, vascular stiffness, conductance of conduit and resistance arteries, and perfusion in the microcirculation. Following 2 weeks of CF intake, FMD improved in young (6.1 ± 0.7 vs. 7.6 ± 0.7 %, p < 0.001) and elderly (4.9 ± 0.6 vs. 6.3 ± 0.9 %, p < 0.001). Secondary outcomes demonstrated in both groups that CF intake decreased pulse wave velocity and lowered total peripheral resistance, and increased arteriolar and microvascular vasodilator capacity, red cell deformability, and diastolic blood pressure, while cardiac output remained affected. In the elderly, baseline systolic blood pressure was elevated, driven by an arterial-stiffness-related augmentation. CF intake decreased aortic augmentation index (−9 %) and thus systolic blood pressure (−7 mmHg; Clinicaltrials.gov: NCT01639781). CF intake reverses age-related burden of cardiovascular risk in healthy elderly, highlighting the potential of dietary flavanols to maintain cardiovascular health.
The purpose of the study was to assess the effects of exercise interventions with different impact loading characteristics on lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) in older adults. We searched electronic databases and hand searched selected journals up to February 2011 for randomized controlled trials (RCTs) investigating the effects of impact exercise interventions on LS and FN BMD in older adults. Exercise protocols were categorized according to impact loading characteristics. Weighted mean difference (WMD) meta-analyses were undertaken. Heterogeneity amongst trials and publication bias was tested. Random-effects models were applied. Trial quality assessment was also undertaken. Nineteen RCTs, including 1577 subjects, met the inclusion criteria. Twenty-two study group comparisons reported BMD data at the LS. Meta-analysis showed a significant change in BMD at this site (WMD 0.011 g/cm2, 95% CI 0.003 to 0.020; p = 0.007), although results were moderately inconsistent (I 2 = 52.2%). BMD data at the FN were available from 19 study group comparisons among older adults. Results were inconsistent (I 2 = 63.6%) in showing a significant positive effect of exercise on BMD at this site (WMD 0.016 g/cm2, 95% CI 0.005 to 0.027; p = 0.004). Combined loading studies of impact activity mixed with high-magnitude joint reaction force loading through resistance training were effective at LS (WMD 0.016 g/cm2, 95% CI 0.002 to 0.036; p = 0.028), and no inconsistency existed among these trials. Odd-impact protocols were also effective in increasing BMD at LS (WMD 0.039 g/cm2, 95% CI 0.002 to 0.075; p = 0.038) and FN (WMD 0.036 g/cm2, 95% CI 0.012 to 0.061; p = 0.004), although heterogeneity was evident (I 2 = 87.5% and I 2 = 83.5%, respectively). We found consistency among results for low-impact and resistance exercise studies on LS and FN, although non-significant BMD changes were evident amongst these types of protocols at any site and amongst the RCTs that provided a combined loading impact exercise at FN. Funnel plots showed no evidence of publication bias. Trial quality was moderate to high. The findings from our meta-analysis of RCTs support the efficacy of exercise for increasing LS and FN BMD in older adults.
The aims of this study were (1) to investigate the participation and performance trends at the ‘100 km Lauf Biel’ in Switzerland from 1998 to 2010, and (2) to compare the age-related changes in 100-km running performance between males and females. For both sexes, the percent of finishers significantly (P < 0.01) decreased for the 18–29 and the 30–39-year age groups, while it significantly (P < 0.01) increased for the 40–49 and the 50–59-year age groups over the studied period. From 1998 to 2010, the mean age of the top ten finishers increased by 0.4 years per annum for both females (P = 0.02) and males (P = 0.003). The running time for the top ten finishers remained stable for females, while it significantly (P = 0.001) increased by 2.4 min per annum for males. There was a significant (P < 0.001) age effect on running times for both sexes. The best 100-km running times was observed for the age comprised between 30 and 49 years for males, and between 30 and 54 years for females, respectively. The age-related decline in running performance was similar until 60–64 years between males and females, but was greater for females compared to males after 65 years. Future studies should investigate the lifespan from 65 to 75 years to better understand the performance difference between male and female master ultra-marathoners.
Frailty is a multidimensional geriatric syndrome characterised by a state of increased vulnerability to disease. Its causes are unclear, limiting opportunities for intervention. Age-related changes to the immune-endocrine axis are implicated. This study investigated the associations between the immune-endocrine axis and frailty as well as mortality 10 years later among men and women aged 65 to 70 years. We studied 254 participants of the Hertfordshire Ageing Study at baseline and 10-year follow-up. At baseline, they completed a health questionnaire and had collection of blood samples for immune-endocrine analysis. At follow-up, Fried frailty was characterised and mortality ascertained. Higher baseline levels of differential white cell counts (WCC), lower levels of dehydroepiandosterone sulphate (DHEAS) and higher cortisol:DHEAS ratio were all significantly associated with increased odds of frailty at 10-year follow-up. Baseline WCC and cortisol:DHEAS clearly discriminated between individuals who went on to be frail at follow-up. We present the first evidence that immune-endocrine biomarkers are associated with the likelihood of frailty as well as mortality over a 10-year period. This augments our understanding of the aetiology of frailty, and suggests that a screening programme at ages 60–70 years could help to identify individuals who are at high risk of becoming frail and who would benefit from early, targeted intervention, for example with DHEA supplementation or anti-inflammatory strategies. Progress towards the prevention of frailty would bring major health and socio-economic benefits at the individual and the population level.