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Background: Recording and coding of ageing syndromes in hospital records is known to be suboptimal. Natural Language Processing algorithms may be useful to identify diagnoses in electronic healthcare records to improve the recording and coding of these ageing syndromes, but the feasibility and diagnostic accuracy of such algorithms are unclear., Methods: We conducted a systematic review according to a predefined protocol and in line with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Searches were run from the inception of each database to the end of September 2023 in PubMed, Medline, Embase, CINAHL, ACM digital library, IEEE Xplore and Scopus. Eligible studies were identified via independent review of search results by two coauthors and data extracted from each study to identify the computational method, source of text, testing strategy and performance metrics. Data were synthesised narratively by ageing syndrome and computational method in line with the Studies Without Meta-analysis guidelines., Results: From 1030 titles screened, 22 studies were eligible for inclusion. One study focussed on identifying sarcopenia, one frailty, twelve falls, five delirium, five dementia and four incontinence. Sensitivity (57.1%-100%) of algorithms compared with a reference standard was reported in 20 studies, and specificity (84.0%-100%) was reported in only 12 studies. Study design quality was variable with results relevant to diagnostic accuracy not always reported, and few studies undertaking external validation of algorithms., Conclusions: Current evidence suggests that Natural Language Processing algorithms can identify ageing syndromes in electronic health records. However, algorithms require testing in rigorously designed diagnostic accuracy studies with appropriate metrics reported., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Senescence is a cell fate that contributes to multiple aging-related pathologies. Despite profound age-associated changes in skeletal muscle (SkM), whether its constituent cells are prone to senesce has not been methodically examined. Herein, using single cell and bulk RNA-sequencing and complementary imaging methods on SkM of young and old mice, we demonstrate that a subpopulation of old fibroadipogenic progenitors highly expresses p16 Ink4a . Administration of a senotherapeutic intervention to old mice countered age-related molecular and morphological changes and improved SkM strength. Finally, we found that the senescence phenotype is conserved in SkM from older humans. Collectively, our data provide compelling evidence for cellular senescence as a hallmark and potentially tractable mediator of SkM aging.p2 Cip1 . Administration of a senotherapeutic intervention to old mice countered age-related molecular and morphological changes and improved SkM strength. Finally, we found that the senescence phenotype is conserved in SkM from older humans. Collectively, our data provide compelling evidence for cellular senescence as a hallmark and potentially tractable mediator of SkM aging.

Ageing is an archetypal translational research topic, spanning a breadth of academic disciplines. This poses challenges for researchers aiming to act upon laboratory findings to develop and implement interventions that directly benefit older people. Divisions between distinct academic research cultures present barriers to collaborative working. We present potential strategies to improve the translation of ageing research with examples of successful projects working across disciplines. Researchers and clinicians in ageing should be supported to develop a translational interest and receive specific training about translational research., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Decline in immune system function (immunosenescence) has been implicated in several age-related disorders. However, little is known about whether alteration in T-cell senescence, a process underlying immunological ageing, is related to muscle health in very old adults (aged ≥85 years). Utilising data from the Newcastle 85+ Study, we aimed to (a) derive and characterise immunosenescence profiles by clustering 13 baseline immunosenescence-related biomarkers of lymphocyte compartments in 657 participants; (b) explore the association between the profiles and 5-year change in muscle strength (grip strength) and physical performance (Timed Up-and-Go test), and (c) determine whether immunosenescence profiles predict 3-year incident sarcopenia. Two distinct clusters were identified; Cluster 1 ('Senescent-like phenotype', n = 421), and Cluster 2 ('Less senescent-like phenotype', n = 236) in individuals with complete biomarker data. Although Cluster 1 was characterised by T-cell senescence (e.g., higher frequency of CD4 and CD8 senescence-like effector memory cells), and elements of the immune risk profile (lower CD4/CD8 ratio, CMV+), it was not associated with change in muscle function over time, or with prevalent or incident sarcopenia. Future studies will determine whether more in-depth characterisation or change in T-cell phenotypes predict the decline in muscle health in late adulthood., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Skeletal muscle aging manifests as a decline in muscle quantity and quality that accelerates with aging, increasing the risk of sarcopenia. Sarcopenia is characterized by a loss of muscle strength and mass, and contributes to adverse health outcomes in older adults. Intervention studies have shown that sarcopenia may be treated by higher protein intake in combination with resistance exercise (RE). In comparison, less is known about the role of whole protein-containing foods in preventing or treating sarcopenia. Liquid milk contains multiple nutrients and bioactive components that may be beneficial for muscle, including proteins for muscle anabolism that, alone or with RE, may have myoprotective properties. However, there is a lack of evidence about the role of milk and its effects on muscle aging. This narrative review considers evidence from three observational and eight intervention studies that used milk or fortified milk, with or without exercise, as an intervention to promote muscle health and function in older adults (aged 50-99 years). The observational studies showed no association between higher habitual milk consumption and muscle-related outcomes. The results of intervention studies using fortified milk in relation to elements of sarcopenia were also negative, with further inconclusive results from the studies using a combination of (fortified) milk and exercise. Although milk contains nutrients that may be myoprotective, current evidence does not show beneficial effects of milk on muscle health in older adults. This could be due to high habitual protein intakes (>1.0 g/kg BW/d) in study participants, differences in the type of milk (low-fat vs whole) and timing of milk consumption, length of interventions, as well as differences in the sarcopenia status of participants in trials. Adequately powered intervention studies of individuals likely to benefit are needed to test the effectiveness of a whole food approach, including milk, for healthy muscle aging., Competing Interests: The authors report no conflict of interest in this work., (© 2020 Granic et al.)

The causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related muscle wasting and weakness termed sarcopenia, which directly impacts physical autonomy and survival. Here, we compare genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 older men from Singapore, Hertfordshire UK and Jamaica. Individuals with sarcopenia reproducibly demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1α/ERRα signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced mitochondrial respiratory complex expression and activity, and low NAD + levels through perturbed NAD + biosynthesis and salvage in sarcopenic muscle. We provide an integrated molecular profile of human sarcopenia across ethnicities, demonstrating a fundamental role of altered mitochondrial metabolism in the pathological loss of skeletal muscle mass and function in older people.

(1) Background: Appetite loss in older people, the 'Anorexia of Aging' (AA), is common, associated with under-nutrition, sarcopenia, and frailty and yet receives little attention. This review had two aims: describe interventions for AA and their effectiveness, and identify the methods of appetite assessment. (2) Methods: Study inclusion: participants aged ≥65, intervention for AA, and appetite assessment, any design, and comparator. Exclusion: studies on specific health cohorts. Searches in four databases with hand searching of references and citing works. Two researchers independently assessed eligibility and quality. (3) Results: Authors screened 8729 titles, 46 full texts. Eighteen articles were included describing nine intervention types: education ( n = 1), exercise ( n = 1), flavor enhancement ( n = 2), increased meal variety ( n = 1), mealtime assistance ( n = 1), fortified food ( n = 1), oral nutritional supplement (ONS) ( n = 8), amino acids ( n = 1), and medication ( n = 2). Three studies evaluated combinations: education + exercise, ONS + exercise, and ONS + medication. Five intervention types exhibited favorable effects on appetite but in single datasets or not replicated. Appetite was assessed predominantly by Likert ( n = 9), or visual analogue scales ( n = 7). (4) Conclusions: A variety of interventions and methods of appetite assessments were used. There was a lack of clarity about whether AA or undernutrition was the intervention target. AA is important for future research but needs standardized assessment so that effectiveness of a range of interventions can be fully explored.

Background: Current evidence that links "healthier" dietary patterns to better measured physical performance is mainly from older populations; little is known about the role of earlier diet. We examined adult diet quality in relation to physical performance at age 60-64 years., Methods: Diet quality was defined using principal component analysis of dietary data collected at age 36, 43, 53, and 60-64. Throughout adulthood, diets of higher quality were characterized by higher consumption of fruit, vegetables, and wholegrain bread. Diet quality scores calculated at each age indicated compliance with this pattern. Physical performance was assessed using chair rise, timed-up-and-go, and standing balance tests at age 60-64. The analysis sample included 969 men and women., Results: In gender-adjusted analyses, higher diet quality at each age was associated with better measured physical performance (all p < .01 for each test), although some associations were attenuated after adjustment for covariates. Diet quality scores were highly correlated in adulthood (0.44 ≤ r ≤ 0.67). However, conditional models showed that higher diet quality at age 60-64 (than expected from scores at younger ages), was associated with faster chair rise speed and with longer standing balance time (adjusted: 0.08 [95% CI: 0.02, 0.15] and 0.07 [0.01, 0.14] SD increase in chair rise speed and balance time, respectively, per SD increase in conditional diet quality; both p < .05)., Conclusions: Higher diet quality across adulthood is associated with better physical performance in older age. Current diet quality may be particularly important for physical performance, suggesting potential for improvements in diet in early older age.

Objective: In patients with mitochondrial DNA (mtDNA) maintenance disorders and with aging, mtDNA deletions sporadically form and clonally expand within individual muscle fibers, causing respiratory chain deficiency. This study aimed to identify the sub-cellular origin and potential mechanisms underlying this process., Methods: Serial skeletal muscle cryosections from patients with multiple mtDNA deletions were subjected to subcellular immunofluorescent, histochemical, and genetic analysis., Results: We report respiratory chain-deficient perinuclear foci containing mtDNA deletions, which show local elevations of both mitochondrial mass and mtDNA copy number. These subcellular foci of respiratory chain deficiency are associated with a local increase in mitochondrial biogenesis and unfolded protein response signaling pathways. We also find that the commonly reported segmental pattern of mitochondrial deficiency is consistent with the three-dimensional organization of the human skeletal muscle mitochondrial network., Interpretation: We propose that mtDNA deletions first exceed the biochemical threshold causing biochemical deficiency in focal regions adjacent to the myonuclei, and induce mitochondrial biogenesis before spreading across the muscle fiber. These subcellular resolution data provide new insights into the possible origin of mitochondrial respiratory chain deficiency in mitochondrial myopathy. Ann Neurol 2018;84:289-301., (© 2018 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Objective: to investigate the associations between initial level and rate of change in grip strength (GS) and all-cause mortality in very old adults (≥85 years) over a 9.6-year follow-up., Methods: prospective mortality data from 845 participants in the Newcastle 85+ Study were analysed for survival in relation to GS (kg, baseline and 5-year mean change) using Cox proportional hazards models., Results: during the follow-up, 636 (75.3%) participants died. Higher baseline GS was associated with a decreased risk of mortality in all participants [hazard ratio (HR) = 0.95, 95% confidence interval (CI): 0.93-0.98, P < 0.001], men (HR = 0.97, 95% CI: 0.95-0.99, P = 0.009) and women (HR = 0.96, 95% CI: 0.94-0.99, P = 0.007) after adjustment for health, lifestyle and anthropometric factors. Overall GS slope had a downward trajectory and was determined in 602 participants: 451 experienced constant decline (negative slope) and 151 had increasing GS (positive slope) over time. Men and women with a negative slope had a 16 and 33% increased risk of mortality, respectively, with every kg/year decline in GS (P ≤ 0.005), and participants with a positive slope had a 31% decreased risk of mortality (P = 0.03) irrespective of baseline GS and key covariates., Conclusion: higher baseline GS and 5-year increase in GS were protective of mortality, whilst GS decline was associated with an increased risk of mortality in the very old over 9.6 years, especially in women. These results add to the biological and clinical importance of GS as a powerful predictor of long-term survival in late life., (© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.)

The concept of multimorbidity has attracted growing interest over recent years, and more latterly with the publication of specific guidelines on multimorbidity by the National Institute for Health and Care Excellence (NICE). Increasingly it is recognised that this is of particular relevance to practitioners caring for older adults, where multimorbidity may be more complex due to the overlap of physical and mental health disorders, frailty and polypharmacy. The overlap of frailty and multimorbidity in particular is likely to be due to the widespread health deficit accumulation, leading in some cases to functional impairment. The NICE guidelines identify 'target groups' who may benefit from a tailored approach to care that takes their multimorbidity into account, and make a number of research recommendations. Management includes a proactive individualised assessment and care plan, which improves quality of life by reducing treatment burden, adverse events, and unplanned or uncoordinated care., (© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: weak hand grip strength in later life is a risk factor for disability, morbidity and mortality and is central to definitions of sarcopenia and frailty. It is unclear whether rate of change in grip strength adds to level of grip strength as a risk factor for poor ageing outcomes., Methods: study participants were 292 community-dwelling men and women whose grip strength was measured during the 1994/5 (average age 67) and 2003/5 (average age 76) phases of the Hertfordshire Ageing Study, UK. Individual rate of change in grip strength was estimated using a residual change method. Mortality was followed-up to 2011 (42 men and 21 women died)., Results: average grip strengths in 2003/5 were 38.4 kg (standard deviation [SD] = 8.1) and 23.7 kg (SD = 6.6) for men and women respectively. Average annualised rates of change in grip strength (2003/5 minus 1994/5) were modest owing to a healthy-participant effect (men: -0.12 kg/y, SD = 0.71; women: 0.08 kg/y, SD = 0.54) but varied widely. Mortality risk varied according to level and rate of change in grip strength (P = 0.03); death rates per 100 person years of follow-up were 6.7 (95% CI: 4.6, 9.6) among participants who lost grip over time and had low grip in 2003/5, in contrast with 0.8 (95% CI: 0.1, 5.8) among participants whose grip changed little over time and remained high in 2003/5., Conclusions: levels of grip strength in later life should be considered in conjunction with estimates of change in grip strength identified by repeat measurement over time. Normative data for longitudinal change in grip strength are required., (© The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Background: There is evidence that the personality traits conscientiousness, extraversion and neuroticism are associated with health behaviours and with risk of various health outcomes. We hypothesised that people who are lower in conscientiousness or extraversion or higher in neuroticism may be at greater risk of frailty in later life., Methods: We used general linear models to examine the prospective relation between personality, assessed using the Midlife Development Inventory, and change in frailty, modelled by a frailty index, in 5314 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing., Results: Men and women with higher levels of neuroticism or lower levels of extraversion or conscientiousness had an increased frailty index score at follow-up. After adjustment for potential confounding or mediating variables, including frailty index score at baseline, the frailty index score at follow-up-which potentially ranges from 0 to 1-was higher by 0.035 (95 % confidence interval 0.018, 0.052) for a standard deviation increase in neuroticism and lower by 0.061 (0.031, 0.091) or 0.045 (0.020, 0.071) for a standard deviation increase in extraversion or conscientiousness, respectively. There was some evidence that the association between extraversion and frailty may be due to reverse causation whereby poorer health affected responses to items in the personality inventory., Conclusions: Higher levels of neuroticism or lower levels of conscientiousness or extraversion may be risk factors for the onset or progression of frailty. Future studies need to replicate these observations in other populations and explore the mechanisms underlying these associations., Competing Interests: Compliance with Ethical Standards Authors’ Statement of Conflict of Interest and Adherence to Ethical Standards Authors Catharine R Gale, Rene Mottus, Ian J Deary, Cyrus Cooper and Avan Aihie Sayer declare that they have no conflict of interest. Ethical approval for the English Longitudinal Study of Ageing was obtained from the Multicentre Research and Ethics Committee. Participants gave written informed consent. Procedures complied with the Helsinki Declaration of 1975 as revised in 2000.

Sarcopenia and frailty are important conditions that become increasingly prevalent with age. Sarcopenia is the loss of muscle mass and function, and frailty can be defined as multi-system impairment associated with increased vulnerability to stressors. There is overlap between the two conditions, especially in terms of the physical aspects of the frailty phenotype: low grip strength, gait speed and muscle mass. These measures have been associated with a wide range of ageing outcomes and can be assessed in the clinical setting. In terms of intervention, there is evidence for the benefit of resistance exercise programmes, although these may not always be feasible. Considerable research into the use of medicines, both existing and new, as well as dietary supplements is ongoing. Finally in order to prevent or delay the development of these conditions, an additional approach is to consider aetiological factors operating across the life course., (© Royal College of Physicians 2016. All rights reserved.)

Background: Weak grip strength (GS) is a key component of sarcopenia and frailty and a powerful predictor of mortality, morbidity and disability. Despite increasing interest in understanding GS across the lifespan, little is known about GS decline in the very old (aged ≥85). We examined trajectories of GS in very old adults and identified the determinants., Methods: GS (kg) was measured four times over 5 years in 319 men and 526 women participating in the Newcastle 85+ Study. A weak GS sub-cohort was identified as having strength of ≤27 kg (men), and ≤16 kg (women) at baseline and follow-up. Mixed models were used to establish trajectories of GS and associated factors in all participants, men and women, and in those with weak GS., Results: Men's mean grip strength was 24.42 (SD = 6.77) kg, and women's 13.23 (4.42) kg (p<0.001) at baseline, with mean absolute change of -5.27 (4.90) kg and -3.14 (3.41), respectively (p<0.001) by 5-year follow-up. In the time-only mixed model, men experienced linear annual decline in GS of -1.13 (0.8) kg (β (SE), p<0.001), whilst women's decline although slower, accelerated by -0.06 (0.02) kg (p = 0.01) over time. In the saturated model, higher baseline physical activity, height, fat-free mass, better self-rated health, and not having arthritis in hand(s) were associated with stronger GS initially in both sexes. Annual GS decline in men and participants with weak GS who were highly physically active was slower by 0.95 and 0.52 kg, respectively compared with inactive counterparts., Conclusion: Grip strength decline in the very old followed linear (men) and curvilinear (women) trends. High levels of physical activity were protective of GS loss in men (but not in women) and in those with weak GS. Thus maintaining muscle strength in later life is important to reduce the morbidity and mortality in the very old., Competing Interests: We have the following interest: The Newcastle 85+ Study was partly funded by Unilever Corporate Research. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Introduction: Reductions in heavy manual work as a consequence of mechanisation might adversely impact muscle strength at older ages. We investigated the association between grip strength at retirement age and lifetime occupational exposure to physically demanding activities. Grip strength is an important predictor of long-term health and physical function in older people., Methods: Grip strength (maximum of three readings in each hand) was measured in men from the Hertfordshire Cohort Study at a single examination when their mean age was 65.8 (SD 2.9) years. Associations with lifetime occupational exposure (ascertained by questionnaire) to three activities (standing/walking ≥ 4 h/day; lifting ≥ 25 kg; and energetic work sufficient to induce sweating) were assessed by multivariable linear regression with adjustment for various potential confounders., Results: Complete data were available from 1418 men who had worked for at least 20 years. After adjustment for age, height and weight, those with longer exposures to walking/standing and heavy lifting had lower grip strength, but the relationship disappeared after further adjustment for confounders. Working at physical intensity sufficient to induce sweating was not significantly associated with grip strength., Conclusions: We found no evidence that physically demanding occupational activities increase hand grip strength at normal retirement age. Any advantages of regular physical occupational activity may have been obscured by unmeasured socioeconomic confounders., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Healthy diet has been associated with better muscle strength and physical performance in cross-sectional studies of older adults but the effect of dietary patterns (DP) on subsequent decline, particularly in the very old (aged 85+), has not been determined., Objective: We investigated the association between previously established DP and decline in muscle strength and physical performance in the very old., Design: 791 participants (61.8% women) from the Newcastle 85+ Study were followed-up for change in hand grip strength (HGS) and Timed Up-and Go (TUG) test over 5 years (four waves 1.5 years apart). Mixed models were used to determine the effects of DP on muscle strength and physical performance in the entire cohort and separately by sex., Results: Previously we have established three DP that varied in intake of red meats, potato, gravy and butter and differed with key health and social factors. HGS declined linearly by 1.59 kgF in men and 1.08 kgF in women (both p<0.001), and TUG slowed by 0.13 log10-transformed seconds (log10-s) in men and 0.11 log10-s in women per wave after adjusting for important covariates (both p<0.001), and also showed a nonlinear change (p<0.001). Men in DP1 ('High Red Meat') had worse overall HGS (β = -1.70, p = 0.05), but men in DP3 ('High Butter') had a steeper decline (β = -0.63, p = 0.05) than men in DP2 ('Low Meat'). Men in DP1 and women in DP3 also had overall slower TUG than those in DP2 (β = 0.08, p = 0.001 and β = 0.06, p = 0.01, respectively), but similar rate of decline after adjusting for sociodemographic, lifestyle, health, and functioning factors. The results for HGS and TUG were not affected by participants' cognitive status., Conclusions: DP high in red meats, potato and gravy (DP1), or butter (DP3) may adversely affect muscle strength and physical performance in later life, independently of important covariates and cognitive status.

Background: weak grip strength is a key component of sarcopenia and is associated with subsequent disability and mortality. We have recently established life course normative data for grip strength in Great Britain, but it is unclear whether the cut points we derived for weak grip strength are suitable for use in other settings. Our objective was to investigate differences in grip strength by world region using our data as a reference standard., Methods: we searched MEDLINE and EMBASE for reporting age- and gender-stratified normative data for grip strength. We extracted each item of normative data and converted it on to a Z-score scale relative to our British centiles. We performed meta-regression to pool the Z-scores and compare them by world region., Findings: our search returned 806 abstracts. Sixty papers met inclusion criteria and reported on 63 different samples. Seven UN regions were represented, although most samples (n = 44) were based in developed regions. We extracted 726 normative data items relating to 96,537 grip strength observations. Normative data from developed regions were broadly similar to our British centiles, with a pooled Z-score 0.12 SDs (95% CI: 0.07, 0.17) above the corresponding British centiles. By comparison, normative data from developing regions were clearly lower, with a pooled Z-score of -0.85 SDs (95% CI: -0.94, -0.76)., Interpretation: our findings support the use of our British grip strength centiles and their associated cut points in consensus definitions for sarcopenia and frailty across developed regions, but highlight the need for different cut points in developing regions., (© The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Background: Sarcopenia is defined as the loss of muscle mass and function with age and is associated with decline in mobility, frailty, falls and mortality. There is considerable interest in understanding the underlying mechanisms. Our aim was to characterise muscle morphology changes associated with sarcopenia among community dwelling older men., Methods: One hundred and five men aged 68-76 years were recruited to the Hertfordshire Sarcopenia Study (HSS) for detailed characterisation of muscle including measures of muscle mass, strength and function. Muscle tissue was obtained from a biopsy of the vastus lateralis for 99 men and was processed for immunohistochemical studies to determine myofibre distribution and area, capillarisation and satellite cell (SC) density., Results: Six (6 %) men had sarcopenia as defined by the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. These men had lower SC density (1.7 cells/mm(2) vs 3.8 cells/mm(2), p = 0.06) and lower SC/fibre ratio (0.02 vs 0.06, p = 0.06) than men without sarcopenia. Although men with sarcopenia tended to have smaller myofibres and lower capillary to fibre ratio, these relationships were not statistically significant., Conclusion: We have shown that there may be altered muscle morphology parameters in older men with sarcopenia. These results have the potential to help identify cell and molecular targets for therapeutic intervention. This work now requires extension to larger studies which also include women.

Background: Demographic trends in developed countries have prompted governmental policies aimed at extending working lives. However, working beyond the traditional retirement age may not be feasible for those with major health problems of ageing, and depending on occupational and personal circumstances, might be either good or bad for health. To address these uncertainties, we have initiated a new longitudinal study., Methods/design: We recruited some 8000 adults aged 50-64 years from 24 British general practices contributing to the Clinical Practice Research Datalink (CPRD). Participants have completed questionnaires about their work and home circumstances at baseline, and will do so regularly over follow-up, initially for a 5-year period. With their permission, we will access their primary care health records via the CPRD. The inter-relation of changes in employment (with reasons) and changes in health (e.g., major new illnesses, new treatments, mortality) will be examined., Discussion: CPRD linkage allows cost-effective frequent capture of detailed objective health data with which to examine the impact of health on work at older ages and of work on health. Findings will inform government policy and also the design of work for older people and the measures needed to support employment in later life, especially for those with health limitations.

Poor appetite is a common problem in older people living at home and in care homes, as well as hospital inpatients. It can contribute to weight loss and nutritional deficiencies, and associated poor healthcare outcomes, including increased mortality. Understanding the causes of reduced appetite and knowing how to measure it will enable nurses and other clinical staff working in a range of community and hospital settings to identify patients with impaired appetite. A range of strategies can be used to promote better appetite and increase food intake.

The growing recognition of sarcopenia, the age-related loss of skeletal muscle mass and function, has highlighted the need to understand more about its etiology. Declines in muscle mass and strength are expected aspects of aging, but there is significant variability between individuals in rates of loss. Although some of these differences can be explained by fixed factors, such as sex, much of the remaining variation is unexplained. This has led to increasing interest in the influence of adult lifestyle, particularly in the effects of modifiable factors such as physical activity and diet, and in identifying intervention opportunities both to prevent and manage sarcopenia. A number of trials have examined the separate effects of increased exercise or dietary supplementation on muscle mass and physical performance of older adults, but less is known about the extent to which benefits of exercise training could be enhanced when these interventions are combined. In a comprehensive review of the literature, we consider 17 studies of older adults (≥65 years) in which combined nutrition and exercise interventions were used to increase muscle strength and/or mass, and achieve improvements in physical performance. The studies were diverse in terms of the participants included (nutritional status, degree of physical frailty), supplementation strategies (differences in nutrients, doses), exercise training (type, frequency), as well as design (duration, setting). The main message is that enhanced benefits of exercise training, when combined with dietary supplementation, have been shown in some trials - indicating potential for future interventions, but that existing evidence is inconsistent. Further studies are needed, particularly of exercise training combined with dietary strategies that increase intakes of a range of nutrients, as well as bioactive non-nutrients, to provide the evidence on which public health and clinical recommendations can be based.

Objective: to examine the prevalence of frailty and disability in people aged 60 and over and the proportion of those with disabilities who receive help or use assistive devices., Methods: participants were 5,450 people aged 60 and over from the English Longitudinal Study of Ageing. Frailty was defined according to the Fried criteria. Participants were asked about difficulties with mobility or other everyday activities. Those with difficulties were asked whether they received help or used assistive devices., Results: the overall weighted prevalence of frailty was 14%. Prevalence rose with increasing age, from 6.5% in those aged 60-69 years to 65% in those aged 90 or over. Frailty occurred more frequently in women than in men (16 versus 12%). Mobility difficulties were very common: 93% of frail individuals had such difficulties versus 58% of the non-frail individuals. Among frail individuals, difficulties in performing activities or instrumental activities of daily living were reported by 57 or 64%, respectively, versus 13 or 15%, respectively, among the non-frail individuals. Among those with difficulties with mobility or other daily activities, 71% of frail individuals and 31% of non-frail individuals said that they received help. Of those with difficulties, 63% of frail individuals and 20% of non-frail individuals used a walking stick, but the use of other assistive devices was uncommon., Conclusions: frailty becomes increasingly common in older age groups and is associated with a sizeable burden as regards difficulties with mobility and other everyday activities., (© The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: low muscle strength is central to geriatric syndromes including sarcopenia and frailty. It is well described in community-dwelling older people, but the epidemiology of grip strength of older people in rehabilitation or long-term care has been little explored., Objective: to describe grip strength of older people in rehabilitation and nursing home settings., Design: cross-sectional epidemiological study., Setting: three healthcare settings in one town., Subjects: hundred and one inpatients on a rehabilitation ward, 47 community rehabilitation referrals and 100 nursing home residents., Methods: grip strength, age, height, weight, body mass index, number of co-morbidities and medications, Barthel score, Mini-Mental State Examination (MMSE), nutritional status and number of falls in the last year were recorded., Results: grip strength differed substantially between healthcare settings for both men and women (P < 0.0001). Nursing home residents had the lowest age-adjusted mean grip strength and community rehabilitation referrals the highest. Broadly higher grip strength was associated in univariate analyses with younger age, greater height and weight, fewer comorbidities, higher Barthel score, higher MMSE score, better nutritional status and fewer falls. However, after mutual adjustment for these factors, the difference in grip strength between settings remained significant. The Barthel score was the characteristic most strongly associated with grip strength., Conclusions: older people in rehabilitation and care home settings had lower grip strength than reported for those living at home. Furthermore grip strength varied widely between healthcare settings independent of known major influences. Further research is required to ascertain whether grip strength may help identify people at risk of adverse health outcomes within these settings.

Background: It is widely believed that females have longer telomeres than males, although results from studies have been contradictory., Methods: We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression., Results: Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p=1.00) or cell type (p=0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error., Conclusions: Telomere length is longer in females than males, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required., (Copyright © 2013. Published by Elsevier Inc.)

Cross-sectional studies show that older people with better cognition tend to walk faster. Whether this association reflects an influence of fluid cognition upon walking speed, vice versa, a bidirectional relationship or the effect of common causes is unclear. We used linear mixed effects models to examine the dynamic relationship between usual walking speed and fluid cognition, as measured by executive function, verbal memory and processing speed, in 2,654 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing. There was a bidirectional relationship between walking speed and fluid cognition. After adjusting for age and sex, better performance on executive function, memory and processing speed was associated with less yearly decline in walking speed over the 6-year follow-up period; faster walking speed was associated with less yearly decline in each cognitive domain; and less yearly decline in each cognitive domain was associated with less yearly decline in walking speed. Effect sizes were small. After further adjustment for other covariates, effect sizes were attenuated but most remained statistically significant. We found some evidence that walking speed and the fluid cognitive domains of executive function and processing speed may change in parallel with increasing age. Investigation of the association between walking speed and cognition earlier in life is needed to better understand the origins of this relation and inform the development and timing of interventions.

The APOE ε2/3/4 genotype has been associated with low-density lipoprotein cholesterol (LDL-C) and Alzheimer disease. However, evidence for associations with measures of cognitive performance in adults without dementia has been mixed, as it is for physical performance. Associations may also be evident in other genotypes implicated in LDL-C levels. As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, genotypic information was obtained for APOE ε2/3/4, rs515135 (APOB), rs2228671 (LDLR) and rs629301 (SORT1) from eight cohorts of adults aged between 44 and 90 + years. We investigated associations with four measures of cognitive (word recall, phonemic fluency, semantic fluency and search speed) and physical capability (grip strength, get up and go/walk speed, timed chair rises and ability to balance) using meta-analyses. Overall, little evidence for associations between any of the genotypes and measures of cognitive capability was observed (e.g. pooled beta for APOE ε4 effect on semantic fluency z score = -0.02; 95 % CI = -0.05 to 0.02; p value = 0.3; n = 18,796). However, there was borderline evidence within studies that negative effects of APOE ε4 on nonverbal ability measures become more apparent with age. Few genotypic associations were observed with physical capability measures. The findings from our large investigation of middle-aged to older adults in the general population suggest that effects of APOE on cognitive capability are at most modest and are domain- and age-specific, while APOE has little influence on physical capability. In addition, other LDL-C-related genotypes have little impact on these traits.

Cross-sectional studies show that frailty is common in older people with cardiovascular disease. Whether older people at higher risk of developing cardiovascular disease are more likely to become frail is unclear. We used multinomial logistic regression to examine the prospective relation between Framingham cardiovascular disease risk scores and incidence of physical frailty or pre-frailty, defined according to the Fried criteria, in 1,726 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing who had no history of cardiovascular disease at baseline. Men and women with higher Framingham cardiovascular risk scores were more likely to become frail over the 4-year follow-up period. For a standard deviation higher score at baseline, the relative risk ratio (95 % confidence interval) for incident frailty, adjusted for sex and baseline frailty status, was 2.76 (2.18, 3.49). There was a significant association between Framingham cardiovascular risk score and risk of pre-frailty: 1.69 (1.46, 1.95). After further adjustment for other potential confounding factors, the relative risk ratios for frailty and pre-frailty were 2.15 (1.68, 2.75) and 1.50 (1.29, 1.74), respectively. The associations were unchanged after excluding incident cases of cardiovascular disease. Separate adjustment for each component of the risk score suggested that no single component was driving the associations between cardiovascular risk score and incident pre-frailty or frailty. Framingham cardiovascular risk scores may be useful for predicting the development of physical frailty in older people. We now need to understand the biological mechanisms whereby cardiovascular risk increases the risk of frailty.

Cross-sectional studies show that higher blood concentrations of inflammatory markers tend to be more common in frail older people, but longitudinal evidence that these inflammatory markers are risk factors for frailty is sparse and inconsistent. We investigated the prospective relation between baseline concentrations of the inflammatory markers C-reactive protein (CRP) and fibrinogen and risk of incident frailty in 2,146 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing. The relationship between CRP and fibrinogen and risk of incident frailty differed significantly by sex (p for interaction terms <0.05). In age-adjusted logistic regression analyses, for a standard deviation (SD) increase in CRP or fibrinogen, odds ratios (95% confidence intervals) for incident frailty in women were 1.69 (1.32, 2.17) and 1.39 (1.12, 1.72), respectively. Further adjustment for other potential confounding factors attenuated both these estimates. For an SD increase in CRP and fibrinogen, the fully-adjusted odds ratio (95% confidence interval) for incident frailty in women was 1.27 (0.96, 1.69) and 1.31 (1.04, 1.67), respectively. Having a high concentration of both inflammatory markers was more strongly predictive of incident frailty than having a high concentration of either marker alone. In men, there were no significant associations between any of the inflammatory markers and risk of incident frailty. High concentrations of the inflammatory markers CRP and fibrinogen are more strongly predictive of incident frailty in women than in men. Further research is needed to understand the mechanisms underlying this sex difference.

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.

Sarcopenia is the age-related loss of skeletal muscle mass and function. It is now recognised as a major clinical problem for older people and research in the area is expanding exponentially. One of the most important recent developments has been convergence in the operational definition of sarcopenia combining measures of muscle mass and strength or physical performance. This has been accompanied by considerable progress in understanding of pathogenesis from animal models of sarcopenia. Well-described risk factors include age, gender and levels of physical activity and this knowledge is now being translated into effective management strategies including resistance exercise with recent interest in the additional role of nutritional intervention. Sarcopenia is currently a major focus for drug discovery and development although there remains debate about the best primary outcome measure for trials, and various promising avenues to date have proved unsatisfactory. The concept of 'new tricks for old drugs' is, however, promising, for example, there is some evidence that the angiotensin-converting enzyme inhibitors may improve physical performance. Future directions will include a deeper understanding of the molecular and cellular mechanisms of sarcopenia and the application of a lifecourse approach to understanding aetiology as well as to informing the optimal timing of interventions.

The association between functioning of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages remains poorly understood. We carried out meta-analyses to test the hypothesis that dysregulation of the HPA axis, as indexed by patterns of diurnal cortisol release, is associated with worse physical performance. Data from six adult cohorts (ages 50-92 years) were included in a two stage meta-analysis of individual participant data. We analysed each study separately using linear and logistic regression models and then used meta-analytic methods to pool the results. Physical performance outcome measures were walking speed, balance time, chair rise time and grip strength. Exposure measures were morning (serum and salivary) and evening (salivary) cortisol. Total sample sizes in meta-analyses ranged from n=2146 for associations between morning Cortisol Awakening Response and balance to n=8448 for associations between morning cortisol and walking speed. A larger diurnal drop was associated with faster walking speed (standardised coefficient per SD increase 0.052, 95% confidence interval (CI) 0.029, 0.076, p<0.001; age and gender adjusted) and a quicker chair rise time (standardised coefficient per SD increase -0.075, 95% CI -0.116, -0.034, p<0.001; age and gender adjusted). There was little evidence of associations with balance or grip strength. Greater diurnal decline of the HPA axis is associated with better physical performance in later life. This may reflect a causal effect of the HPA axis on performance or that other ageing-related factors are associated with both reduced HPA reactivity and performance., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: There is a growing literature that links greater duration and exclusivity of breastfeeding to beneficial effects on adult health outcomes. Muscle growth in the neonatal period may be very sensitive to variations in early nutrition, but little is known about long-term effects of infant feeding on muscle strength., Methods: In 2,983 community-dwelling older men and women born 1931-1939, we examined the relationship between their type of milk feeding in infancy and their muscle strength in adult life. Information about milk feeding for each participant was abstracted from their infant record; grip strength was measured using a Jamar dynamometer., Results: Sixty percent (1,783) of the participants were breastfed only, 31% (926) were breast- and bottle-fed, and 9% (274) were bottle-fed only. There were no differences in type of milk feeding between men and women or according to social class at birth. Among the men studied, grip strength was related to the type of milk feeding, such that greater exposure to breast milk in infancy was associated with greater grip strength in adult life (p = .023). This association remained after adjustment for the effects of a range of confounding influences (birthweight, infant growth, height, age at measurement, adult diet, and level of physical activity). In contrast, the type of milk feeding in infancy was not related to grip strength among the women studied (p = .807)., Conclusions: These data suggest that in men, differences in nutritional exposure in the early postnatal period may have lifelong implications for muscle strength.

Background and Aims: Muscle strength may decline with age differentially in the upper and lower limbs. This information is difficult to capture through a single measure. The present study therefore aimed to characterize the relative changes in handgrip and lower limb muscle strength with aging by expressing them as a ratio., Methods: Thirty-eight healthy volunteers aged 20-82 years performed maximal voluntary contractions (MVC) of quadriceps and handgrip using a custom-built transducer and a Jamar dynamometer respectively., Results: The grip-quadriceps ratios for young adults was similar in males and females (0.75); indicating knee extensor force exceeded grip force by approximately 25%. Ratios were increased in older adults (p=0.05), and strength of the two muscle groups was approximately equal (1.1). Pearson's correlation coefficients for grip against quadriceps strength were r=0.63 (young males), r=0.83 (young females), r=0.35 (older males) and r=0.05 (older females)., Conclusions: The ratio used demonstrated clear differences between the age groups. The reduced muscle strength with increasing age was expected, but the higher grip/quadriceps strength ratios quantify a greater loss of quadriceps than grip strength with aging. It remains to be investigated whether the relatively greater rate of decline in quadriceps strength seen in healthy older people is more exaggerated in those who are frail, which would have implications for using grip strength as a physical marker of lower limb strength and function in those at risk of immobility and falls.

Background: Age-related hearing loss is a common disabling condition but its causes are not well understood and the role of inflammation as an influencing factor has received little consideration in the literature., Objective: To investigate the association between inflammatory markers and hearing in community-dwelling older men and women., Design: Cross-sectional analysis within a cohort study., Setting: The Hertfordshire Ageing Study., Participants: A total of 343 men and 268 women aged 63-74 years on whom data on audiometric testing, inflammatory markers and covariates were available at follow-up in 1995., Main Outcome Measures: Average hearing threshold level (across 500-4,000 Hz) of the worst hearing ear and audiometric slope in dB/octave from 500 to 4,000 Hz., Results: Older age, smoking, history of noise exposure and male gender (all P < 0.001) were associated with higher mean hearing threshold in the worse ear in univariate analysis. After adjustment for these factors in multiple regression models, four measures of immune or inflammatory status were significantly associated with hearing threshold, namely white blood cell count (r = 0.13, P = 0.001), neutrophil count (r = 0.13, P = 0.002), IL-6 (r = 0.10, P = 0.05) and C-reactive protein (r = 0.11, P = 0.01). None of the inflammatory markers was associated with maximum audiometric slope in adjusted analyses., Conclusions: Markers of inflammatory status were significantly associated with degree of hearing loss in older people. The findings are consistent with the possibility that inflammatory changes occurring with ageing may be involved in age-related hearing loss. Longitudinal data would enable this hypothesis to be explored further.

Background: Low muscle mass and function have been associated with poorer indicators of physical capability in older people, which are in-turn associated with increased mortality rates. The growth hormone/insulin-like growth factor (GH/IGF) axis is involved in muscle function and genetic variants in genes in the axis may influence measures of physical capability., Methods: As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women from seven UK cohorts aged between 52 and 90 years old were genotyped for six polymorphisms: rs35767 (IGF1), rs7127900 (IGF2), rs2854744 (IGFBP3), rs2943641 (IRS1), rs2665802 (GH1) and the exon-3 deletion of GHR. The polymorphisms have previously been robustly associated with age-related traits or are potentially functional. Meta-analysis was used to pool within-study genotypic effects of the associations between the polymorphisms and four measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance., Results: Few important associations were observed among the several tests. We found evidence that rs2665802 in GH1 was associated with inability to balance for 5 s (pooled odds ratio per minor allele = 0.90, 95% CI: 0.82-0.98, p-value = 0.01, n = 10,748), after adjusting for age and sex. We found no evidence for other associations between the polymorphisms and physical capability traits., Conclusion: Our findings do not provide evidence for a substantial influence of these common polymorphisms in the GH/IGF axis on objectively measured physical capability levels in older adults.

Several age-related traits are associated with shorter telomeres, the structures that cap the end of linear chromosomes. A common polymorphism near the telomere maintenance gene TERT has been associated with several cancers, but relationships with other aging traits such as physical capability have not been reported. As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and women aged between 44 and 90 years from nine UK cohorts were genotyped for the single-nucleotide polymorphism (SNP) rs401681. We then investigated relationships between the SNP and 30 age-related phenotypes, including cognitive and physical capability, blood lipid levels and lung function, pooling within-study genotypic effects in meta-analyses. No significant associations were found between the SNP and any of the cognitive performance tests (e.g. pooled beta per T allele for word recall z-score = 0.02, 95% CI: -0.01 to 0.04, P-value = 0.12, n = 18,737), physical performance tests (e.g. pooled beta for grip strength = -0.02, 95% CI: -0.045 to 0.006, P-value = 0.14, n = 11,711), blood pressure, lung function or blood test measures. Similarly, no differences in observations were found when considering follow-up measures of cognitive or physical performance after adjusting for its measure at an earlier assessment. The lack of associations between SNP rs401681 and a wide range of age-related phenotypes investigated in this large multicohort study suggests that while this SNP may be associated with cancer, it is not an important contributor to other markers of aging., (© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.)

Background: Sarcopenia is defined as the loss of muscle mass and strength with age. Although a number of adult influences are recognised, there remains considerable unexplained variation in muscle mass and strength between older individuals. This has focused attention on influences operating earlier in life. Our objective for this study was to identify life course influences on muscle mass and strength in an established birth cohort and develop methodology for collection of muscle tissue suitable to investigate underlying cellular and molecular mechanisms., Methods: One hundred and five men from the Hertfordshire Cohort Study (HCS), born between 1931 and 1939 who have historical records of birth weight and weight at one year took part in the Hertfordshire Sarcopenia Study (HSS). Each participant consented for detailed characterisation of muscle mass, muscle function and aerobic capacity. In addition, a muscle biopsy of the vastus lateralis using a Weil-Blakesley conchotome was performed. Data on muscle mass, function and aerobic capacity was collected on all 105 participants. Muscle biopsy was successfully carried out in 102 participants with high rates of acceptability. No adverse incidents occurred during the study., Discussion: The novel approach of combining epidemiological and basic science characterisation of muscle in a well established birth cohort will allow the investigation of cellular and molecular mechanisms underlying life course influences on sarcopenia.

Background: dietary patterns analysis takes account of the combined effects of foods and may be a more meaningful way of assessing dietary exposure than considering individual nutrients. Little is known about the dietary patterns of older adults in the UK., Objective: to describe the dietary patterns of a population of community-dwelling older men and women and to examine factors associated with compliance with these patterns., Setting and Participants: 3,217 men and women aged 59-73 years who were participants in the Hertfordshire Cohort Study., Methods: diet was assessed using an administered food frequency questionnaire; dietary patterns were identified using principal component analysis., Results: two dietary patterns were identified. The first was characterised by high consumption of fruit, vegetables, oily fish and wholemeal cereals ('prudent' pattern); the second was characterised by high consumption of vegetables, processed and red meat, fish and puddings ('traditional' pattern). High 'prudent' diet scores were more common in women, in men and women in non-manual classes and in non-smokers (all P < 0.05), whilst high 'traditional' diet scores were more common in men, in men and women who had partners and were associated with higher alcohol consumption (all P < 0.05)., Conclusions: we have described large variations in food consumption and nutrient intake amongst older adults that are likely to have implications for future health. The specific socio-demographic correlates of the dietary patterns provide insights into the contexts within which good and poor diets exist, and may help in the identification of opportunities for dietary intervention.

Background: Reduced physical performance and physical activity have serious health consequences, but adult determinants do not fully explain variation in older people., Objective: Our objective was to investigate the relationship between early growth, physical performance and physical activity in older people., Methods: We studied 349 men and 280 women born 1931-1939 with known birth weight and weight at 1 year who were taking part in the Hertfordshire Cohort Study, UK. Physical performance was measured (3-m walk, chair rises and standing balance) and physical activity was assessed by questionnaire and converted to estimated energy expenditure., Results: Poor balance was associated with lower birth weight (odds ratio [OR] for poor balance per standard deviation [SD] increase in birth weight = 0.68, p=0.01) and weight at 1 year (OR for poor balance per SD increase in weight at 1 year=0.67, p=0.03) after adjustment for age and current size in men, but not in women. There were no significant positive relationships between early size and growth and the other measures of physical performance or physical activity in men or women., Conclusion: Current lifestyle factors, particularly those affecting adult weight, may be more important than developmental influences on most measures of physical performance and physical activity in older people., (Copyright 2008 S. Karger AG, Basel.)

Objectives: To examine relationships between diet and grip strength in older men and women and to determine whether prenatal growth modifies these relationships., Design: Cross-sectional and retrospective cohort study., Setting: Hertfordshire, United Kingdom., Participants: Two thousand nine hundred eighty-three men and women aged 59 to 73 who were born and still living in Hertfordshire, United Kingdom., Measurements: Weight at birth recorded in Health Visitor ledgers; current food and nutrient intake assessed using an administered food frequency questionnaire; and grip strength measured using a handheld dynamometer., Results: Grip strength was positively associated with height and weight at birth and inversely related to age (all P<.001). Of the dietary factors considered in relation to grip strength, the most important was fatty fish consumption. An increase in grip strength of 0.43 kg (95% confidence interval (CI)=0.13-0.74) in men (P=.005) and 0.48 kg (95% CI=0.24-0.72) in women (P<.001) was observed for each additional portion of fatty fish consumed per week. These relationships were independent of adult height, age, and birth weight, each of which had additive effects on grip strength. There was no evidence of interactive effects of weight at birth and adult diet on grip strength., Conclusion: These data suggest that fatty fish consumption can have an important influence on muscle function in older men and women. This raises the possibility that the antiinflammatory actions of omega-3 fatty acids may play a role in the prevention of sarcopenia.

Somatic mutation in the mitochondrial genome occurs much more rapidly than in the nuclear genome and is a feature, possibly contributory, of the aging of cells and tissues. Identifying mitochondrial sequence changes in blood DNA of elderly subjects may provide a maker for the epigenetic changes of mitochondrial DNA known to occur in tissues with lower cellular turnover, and would also have implications for immunosenescence. No large-scale epidemiological studies have been reported previously. In this study we have established long-PCR banks of the mitochondrial genome from peripheral lymphocytes for an elderly cohort of 716 individuals with a range of measured aging phenotypes, and we have established assays for three widely reported mutations: the 4977 bp and 8048 bp deletions and point mutation A3243G. No individuals were identified with detectable heteroplasmy for these changes. Implications for tissue and population prevalence are discussed. The mitochondrial long-PCR DNA banks established will be useful for a wide range of studies of somatic mutation and of germline haplotypes in relation to aging.

The modification of ageing by nutritional intervention is well recognised. Post-weaning diet restriction is the only widely reproducible method to slow ageing, but the effects of prenatal and preweaning diet restriction have been less well characterised. There is some evidence that diet restriction instituted in utero or shortly after birth may have an opposite effect and be associated with increased ageing, and recent work suggests that it may shorten lifespan. Interest in this area has been rekindled by the growing body of epidemiological evidence showing that a number of age-related diseases are associated with poor growth and inadequate nutrition in early life. The relevance of this association to structural and functional ageing changes in different systems is now being considered. Work on musculo-skeletal ageing has demonstrated that loss of muscle strength and bone mass is greater in individuals who did not grow well in early life, and a range of studies suggests that maternal, developmental and nutritional factors are important. The underlying mechanisms remain speculative, and it remains to be determined whether they are system-specific or universal throughout the body. A new cohort of subjects aged between 60 and 70 years is being established to investigate how genetic factors interact with growth and nutritional influences to programme musculo-skeletal ageing in later life.

Background: epidemiological studies have shown that poor early growth is associated with cardiovascular and other degenerative diseases. This has been explained by programming, whereby undernutrition and other influences which restrict early growth permanently change the structure and physiology of the body. The long-term effects of poor early nutrition on ageing have been demonstrated in animals but not studied in man., Objectives: to determine if poor early growth was associated with increased markers of ageing in later life., Methods: we traced 1428 men and women, born in Hertfordshire between 1920 and 1930, for whom records of early weight were available. 824 (58%) were interviewed at home and 717 (50%) attended clinic for eye examination, audiometry, grip strength measurement, skin thickness ultrasound and anthropometry., Results: lower weight at 1 year was associated with increased lens opacity score, higher hearing threshold, reduced grip strength and thinner skin. Visual acuity, macular degeneration and intraocular pressure were not related to early growth., Conclusions: the associations between early growth and markers of ageing suggest that in some systems, ageing may be programmed by events in early life. A potential mechanism is the impaired development of repair systems.

We investigated the relationship between visual acuity, early growth and eye disease in a retrospective cohort study of 700 individuals in North Hertfordshire. Records of birth weight and weight at one year were used to determine early growth. We measured visual acuity and age-related eye diseases using standard instruments in those same individuals (now aged 63 to 73). Visual acuity below the legal threshold for driving in the UK (6/11 or poorer) was present in 13% of subjects. There was no clear association between birth weight or weight at one year and visual acuity. Vision impairment was found to be associated with refractive error, cataract, age-related maculopathy, and elevated macular threshold. After controlling for the effects of eye disease, increasing age remained a significant predictor of poorer visual acuity.