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The epigenome has been shown to deteriorate with age, potentially impacting on ageing-related disease. tRNA, while arising from only ˜46 kb (<0.002% genome), is the second most abundant cellular transcript. tRNAs also control metabolic processes known to affect ageing, through core translational and additional regulatory roles. Here, we interrogate the DNA methylation state of the genomic loci of human tRNA. We identify a genomic enrichment for age-related DNA hypermethylation at tRNA loci. Analysis in 4,350 MeDIP-seq peripheral-blood DNA methylomes (16-82 years), identifies 44 and 21 hypermethylating specific tRNAs at study-and genome-wide significance, respectively, contrasting with none hypomethylating. Validation and replication (450k array and independent targeted Bisuphite-sequencing) supported the hypermethylation of this functional unit. Tissue-specificity is a significant driver, although the strongest consistent signals, also independent of major cell-type change, occur in tRNA-iMet-CAT-1-4 and tRNA-Ser-AGA-2-6. This study presents a comprehensive evaluation of the genomic DNA methylation state of human tRNA genes and reveals a discreet hypermethylation with advancing age.

Osteosarcopenia is a newly described syndrome that describes the co-existence of osteoporosis and sarcopenia, two chronic musculoskeletal conditions associated with ageing. Osteoporosis, a condition of low bone mass and micro-architectural deterioration of bone, and sarcopenia, the loss of muscle mass, strength and function, often co-exist in a frail subset of the elderly population, leading to significantly worsened outcomes than seen in either condition alone. These include a greater risk of falls, fractures and institutionalization, and significant socioeconomic costs. With our ageing population, osteosarcopenia is a public health concern that will become increasingly relevant in the future. Its aetiology is multifactorial, with mechanical, biochemical, genetic and lifestyle factors all contributing to involution of the 'bone-muscle unit'. Improved understanding of the interactions between muscle and bone could facilitate the development of new therapeutic agents which target muscle and bone as one. Together with existing pharmacological, nutritional and exercise-based therapies, this should enable a more holistic approach to osteosarcopenia in the future.

Characterisation of grip strength (GS) using isometric dynamometry is central to the definition of sarcopenia. Determinants of low GS include: older age, shorter stature, low physical activity, poor nutrition, socioeconomic disadvantage and multimorbidity. Less is known about risk factors for accelerated loss of GS. We investigated determinants of level and 8-year loss of GS in 3703 men and women (aged 52-82 years) in the English Longitudinal Study of Ageing (ELSA). Four hundred and forty-one men and women (aged 59-71 years) who participated in a 10-year follow-up of the Hertfordshire Cohort Study (HCS) were used for replication. Variables were harmonised between cohorts. Change in GS was characterised using mixed-effects models in ELSA and a residual change approach in HCS and analysed for men and women combined. Men in ELSA and HCS had higher average levels of GS at baseline, and accelerated rates of loss, compared with women. In ELSA, older age, shorter stature and multimorbidity were correlated with lower level, and accelerated rate of loss, of GS in both sexes (accelerated loss of 0.04 (95% CI 0.00-0.08) standard deviation scores per additional morbidity after multivariable adjustment). Socioeconomic disadvantage, low level of physical activity and poorer self-reported health were also correlated with low GS level, but not loss rate, after multivariable adjustment. Analysis in HCS yielded similar results. Our results identify multimorbidity as a modifiable determinant of loss of muscle strength in later life, and raise the possibility that developmental influences may impact on rate of involutional decline in muscle strength.

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: poor diet quality is common among older people, but little is known about influences on food choice, including the role of psychosocial factors at this age., Objective: to identify psychosocial correlates of diet quality in a community-dwelling population of men and women aged 59-73 years; to describe relationships with change in diet quality over 10 years., Design: Longitudinal cohort, Hertfordshire Cohort Study (HCS)., Subjects: HCS participants assessed at baseline (1998-2003: 1,048 men, 862 women); 183 men and 189 women re-assessed in 2011., Methods: diet was assessed by administered food frequency questionnaire; diet scores were calculated to describe diet quality at baseline and follow-up. A range of psychosocial factors (social support, social network, participation in leisure activities, depression and anxiety, sense of control) were assessed by questionnaire., Results: at baseline, better diet quality was related to a range of social factors, including increased confiding/emotional social support (men and women), practical support (men) and a larger social network (women) (all P < 0.05). For both men and women, greater participation in social and cognitive leisure activities was related to better diet quality (P < 0.005). There were few associations between measured psychosocial factors at baseline and change in diet score over 10 years, in the follow-up sub-group. However, greater participation in leisure activities, especially cognitive activities, at baseline was associated with smaller declines in diet quality over the 10-year follow-up period for both men (P = 0.017) and women (P = 0.014)., Conclusions: in community-dwelling older adults, a range of social factors, that includes greater participation in leisure activities, were associated with diets of better quality., (© 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)

The world is aging. The population aged over sixty years worldwide is predicted to rise from 841 million in 2013 to more than 2 billion by 2050. Musculoskeletal (MSK) disease is a significant burden on the aging population, contributing 7.5% of the disease burden in those aged over 60 years. MSK diseases have a pronounced effect on disability level and independence in old age, with a consequent significant public health burden and impact on quality of later life. As numbers of older individuals and their disease burden increase, it is important to examine MSK disease in older life in detail. The musculoskeletal aging phenotype comprises four often interwoven key elements - osteoporosis, osteoarthritis, sarcopenia and frailty - and this review will focus on these four themes. It is crucial that we are able to accurately measure each phenotype in order that we might identify those individuals at greatest risk of developing these conditions, and design trials of therapeutic agents that might impact their development. Accurate measurement of the musculoskeletal aging phenotype is necessary firstly to document the burden of each condition, and then to enable factors to be identified which may accelerate or retard their development or progression. In some areas of MSK disease, this work is more advanced (osteoporosis); in other areas (sarcopenia) the field is currently very rapidly evolving. We will explore the tools currently used to measure the musculoskeletal aging phenotype and how they compare, as well as highlight areas where more work is needed., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Loss of bone and muscle with advancing age represent a huge threat to loss of independence in later life. Osteoporosis represents a major public health problem through its association with fragility fractures, primarily of the hip, spine and distal forearm. Sarcopenia, the age related loss of muscle mass and function, may add to fracture risk by increasing falls risk. In the context of muscle aging, it is important to remember that it is not just a decline in muscle mass which contributes to the deterioration of muscle function. Other factors underpinning muscle quality come into play, including muscle composition, aerobic capacity and metabolism, fatty infiltration, insulin resistance, fibrosis and neural activation. Genetic, developmental, endocrine and lifestyle factors, such as physical activity, smoking and poor diet have dual effects on both muscle and bone mass in later life and these will be reviewed here. Recent work has highlighted a possible role for the early environment. Inflammaging is an exciting emerging research field that is likely to prove relevant to future work, including interventions designed to retard to reverse bone and muscle loss with age., (© 2015 Wiley Periodicals, Inc.)

Introduction: sarcopenia is associated with adverse health outcomes. The aim of this study was to describe the prevalence of sarcopenia in community-dwelling older people in the UK using the European Working Group on Sarcopenia in Older People (EWGSOP) consensus definition., Methods: we applied the EWGSOP definition to 103 community-dwelling men participating in the Hertfordshire Sarcopenia Study (HSS) using both the lowest third of dual-energy X-ray absorptiometry (DXA) lean mass (LM) and the lowest third of skin-fold-based fat-free mass (FFM) as markers of low muscle mass. We also used the FFM approach among 765 male and 1,022 female participants in the Hertfordshire Cohort Study (HCS). Body size, physical performance and self-reported health were compared in participants with and without sarcopenia., Results: the prevalence of sarcopenia in HSS men (mean age 73 years) was 6.8% and 7.8% when using the lowest third of DXA LM and FFM, respectively. DXA LM and FFM were highly correlated (0.91, P < 0.001). The prevalence of sarcopenia among the HCS men and women (mean age 67 years) was 4.6% and 7.9%, respectively. HSS and HCS participants with sarcopenia were shorter, weighed less and had worse physical performance. HCS men and women with sarcopenia had poorer self-reported general health and physical functioning scores., Conclusions: this is one of the first studies to describe the prevalence of sarcopenia in UK community-dwelling older people. The EWGSOP consensus definition was of practical use for sarcopenia case finding. The next step is to use this consensus definition in other ageing cohorts and among older people in a range of health-care settings.

Background: reduced grip strength is associated with adverse health consequences, and there is interest in identifying modifiable influences. Cardiovascular drugs are commonly used by older people, but their effect on muscle strength is unclear., Methods: we investigated associations between cardiovascular drug use and grip strength among 1,572 men and 1,415 women, aged 59-73, who participated in the Hertfordshire Cohort Study., Results: Forty-five percent of participants were taking a cardiovascular drug. Furosemide was associated with average decreases in grip strength of 3.15 kg (95% confidence interval [CI] 0.90, 5.39, P < 0.01) among men and 2.35 kg (95% CI 0.93, 3.77, P < 0.01) among women after adjustment for age and height. Corresponding differences for nitrates were 1.84 kg (95% CI 0.29, 3.39, P = 0.02) among men and 3.66 kg (95% CI 1.99, 5.33, P < 0.01) among women. Calcium channel blockers and fibrates were associated with reduced grip among women. Statins were not associated with grip. The associations between grip strength and nitrate use in men and nitrate and fibrate use in women were robust to additional adjustment for co-morbidity., Conclusions: use of some cardiovascular drugs is associated with reduced grip strength in older people. These findings have potential implications for the functional ability of older people treated with these drugs.

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.)

In humans, cortisol and GH are secreted in a pulsatile manner, and an interaction between GH and the hypothalamic-pituitary-adrenal axis has been established. In view of the sexually dimorphic pattern in GH secretion, we investigated the GH-cortisol bihormonal secretory dynamics in male and female healthy older individuals. We studied the GH and cortisol secretory patterns in 83 healthy subjects (45 men and 38 women; age range, 59.4-73.0 yr) by determining serum GH and cortisol concentrations at 20-min intervals for 24 h. The irregularity of GH and cortisol secretion was assessed using approximate entropy (ApEn), a scale- and model-independent statistic. The synchrony of joint GH-cortisol spontaneous secretion was quantified using the cross-ApEn statistic. Cross-correlation analysis of GH and cortisol patterns was computed at various time lags covering the 24-h period. Mean 24-h serum GH concentrations were significantly higher in females (mean, 1.31 mU/L; SD, 0.87) than in males (mean, 0.88 mU/L; SD, 0.42; P = 0.009), whereas mean 24-h serum total cortisol concentrations were higher in males (mean, 9.0 microg/dL; SD, 1.4) than in females (mean, 7.3 microg/dL; SD, 1.4; P = 0.0001). GH secretion was more irregular in females (mean ApEn, 0.81; SD, 0.23) than in males (mean ApEn, 0.60; SD, 0.20; P < 0.001). No significant difference in the regularity of cortisol secretion was noted between sexes. Cross-ApEn values of paired GH-cortisol were higher in females (mean, 1.15; SD, 0.18) than in males (mean, 1.01; SD, 0.16; P = 0.0003). Stepwise multiple linear regression analysis indicated that estradiol and insulin-like growth factor-binding protein-3 concentrations were independently related to GH ApEn values (r(2) = 0.14; P = 0.01), whereas cross-ApEn values of paired GH-cortisol were best predicted by FSH concentrations (r(2) = 0.37; P = 0.003). Cross-correlation analysis revealed a significant positive correlation between GH and cortisol, peaking at lag time of 4.7 h in males (r = 0.30; P < 0.0001) and 4.3 h in females (r = 0.14; P < 0.0001), with GH leading cortisol by these time intervals. In addition, a significant negative correlation between the two hormones was noted over time, peaking at 4.7 h in males (r = -0.21; P < 0.0001) and 6.3 h in females (r = -0.25; P < 0.0001), with cortisol leading GH by these time intervals. The above results indicate that in the elderly, females have a more disordered GH secretory pattern and a more asynchronous joint GH-cortisol secretion than their male counterparts. These observations most likely reflect bidirectional interactions between the GH and hypothalamic-pituitary-adrenal axis in humans as well as diminution of subsystem integrity and synchronous control of interconnected hormonal systems with advancing age.

Exogenous glucocorticoids are known to increase the risk of osteoporosis. However, the contribution made by endogenous circulating cortisol concentrations to adult skeletal status remains unknown. We examined this issue in a sample of 34 healthy men, aged 61-72 yr. Venous blood samples were obtained under standard conditions every 20 min over a 24-h period. Measurements were made of serum cortisol and cortisol-binding globulin. Bone mineral density was measured at the lumbar spine and proximal femur using dual energy x-ray absorptiometry. Measurements were made at baseline and 4 yr later. There was a weak negative association between integrated cortisol concentration and lumbar spine bone density (r = -0.37; P < 0.05); similar relationships (P < 0.05) existed at three of five proximal femoral sites. There were also statistically significant positive associations between the trough cortisol concentration and bone loss rate at the lumbar spine (r = 0.38; P < 0.05), femoral neck (r = 0.47; P < 0.001), and the trochanteric region (r = 0.41; P = 0.02) over the 4-yr follow-up period. The cross-sectional relationships between cortisol concentration and bone density were removed by adjustment for body mass index, but the influence on bone loss rate remained significant after adjusting for adiposity, cigarette smoking, alcohol consumption, dietary calcium intake, physical activity, and serum testosterone and estradiol levels. These observations suggest that the endogenous cortisol profile of healthy elderly men is a determinant of their bone mineral density and their rate of involutional bone loss.

Epidemiological studies suggest that retarded growth in infancy is associated with low adult bone mass. The mechanism underlying this association is unknown, but the programming of GH secretion or sensitivity by environmental influences during early development may play a role. We examined this issue in a sample of 37 healthy men, aged 63-73 yr, whose weight gain in infancy had been recorded. Venous blood samples were obtained under standard conditions every 20 min over a 24-h period. Measurements were made of the GH secretory profile, insulin-like growth factor I (IGF-I), IGF-binding protein-1 and -3, and GH-binding protein. Bone mineral density was measured at the lumbar spine and femoral neck using dual energy x-ray absortiometry. There was a statistically significant association between peak GH concentration (r = 0.46; P < 0.01) and fasting IGF-I concentration (r = 0.46; P < 0.01) with femoral neck bone density. After allowing for the peak GH concentration, median GH was negatively (P < 0.05) associated with bone mineral density. Weight at 1 yr was not related to peak GH, but was strongly related to the median GH concentration (r = 0.42; P = 0.01). These observations are consistent with a dual effect of GH secretion on bone density. High peak GH values drive IGF-I production and maintain bone mineralization in adult life. However, integrated GH secretion, after adjusting for the effect of pulse amplitude, is negatively associated with bone density in adult life. This particular characteristic of the GH secretory profile correlates with growth during infancy and might be programmed by environmental factors during intrauterine or early postnatal life.

PurposeTo conduct a review of the current state of the evidence for rehabilitation strategies post-fragility fracture.MethodsNarrative review conducted by the Rehabilitation Working Group of the International Osteoporosis Foundation Committee of Scientific Advisors characterizing the range of rehabilitation modalities instrumental for the management of fragility fractures.ResultsMulti-modal exercise post-fragility fracture to the spine and hip is strongly recommended to reduce pain, improve physical function, and improve quality of life. Outpatient physiotherapy post-hip fracture has a stronger evidence base than outpatient physiotherapy post-vertebral fracture. Appropriate nutritional care after fragility fracture provides a large range of improvement in morbidity and mortality. Education increases understanding of osteoporosis which in turn increases utilization of other rehabilitation services. Education may improve other health outcomes such as pain and increase a patient's ability for self-advocacy.ConclusionRehabilitation interventions are inter-reliant, and research investigating the interaction of exercise, nutrition, and other multi-modal therapies may increase the relevance of rehabilitation research to clinical care.

We investigated the relationship between lower limb osteoarthritis (OA) and muscle strength and power (assessed by jumping mechanography) in UK community-dwelling older adults. We recruited 249 older adults (144 males, 105 females). OA was assessed clinically at the knee according to ACR criteria and radiographically, at the knee and hip, using Kellgren and Lawrence grading. Two-footed jumping tests were performed using a Leonardo Mechanography Ground Reaction Force Platform to assess maximum muscle force, power and Esslinger Fitness Index. Linear regression was used to assess the relationship between OA and jumping outcomes. Results are presented as β (95% confidence interval). The mean age of participants was 75.2 years (SD 2.6). Males had a significantly higher maximum relative power during lift off (mean 25.7 W/kg vs. 19.9 W/kg) and maximum total force during lift off (mean 21.0 N/kg vs. 19.1 N/kg) than females. In adjusted models, we found significant associations in males between clinical knee OA and maximum relative power [- 6.00 (CI - 9.10, - 2.94)] and Esslinger Fitness Index [- 19.3 (- 29.0, - 9.7)]. In females, radiographic knee OA was associated with total maximum power [- 2.0 (- 3.9, - 0.1)] and Esslinger Fitness Index [- 8.2 (- 15.9, - 0.4)]. No significant associations were observed for maximum total force. We observed significant negative associations between maximum relative power and Esslinger Fitness Index and clinical knee OA in males and radiographic knee OA in females. We have used novel methodology to demonstrate relationships between muscle function and OA in older adults. [ABSTRACT FROM AUTHOR]

Osteoporosis is a common condition which mainly affects older individuals and is more common in women than in men. Rates vary significantly across the world with higher rates in Northern Europe, North America, and Australasia. There are also differences by country and sometimes on a more local level. This review describes the variation and explores how secular trends in fracture rates have changes over recent years and may alter in the future. Although overall rates tend to be increasing, due largely to an ageing population, age-specific rates appear to be declining in some areas. This has considerable importance for the socioeconomic burden of the disease in years to come. Osteoporotic fractures are associated with significant morbidity and in some cases mortality. Consequently, they often require hospital treatment and may lead to long-term institutional care. This leads not only to effects on the individual's quality of life but also to major health care and social costs. [ABSTRACT FROM AUTHOR]