Advances in our understanding of the biology of skeletal muscle ageing are being made at pace, with great potential for these findings to inform the identification of novel treatments for sarcopenia. However, translation of findings from animal models to humans has been hampered by limitations of existing human muscle biopsy studies. Devised to directly address this challenge, the Muscle Ageing and Sarcopenia Study (MASS) Lifecourse is a unique resource for the study of human muscle ageing across adulthood. This deep-phenotyped observational study of 260 community-dwelling men and women aged 18 to 85 years living in North East England includes muscle biopsy samples and detailed characterisation of physical function, health status and sociodemographic and behavioural risk factors. Underpinned by broad interdisciplinary research and clinical expertise this study is catalysing cutting-edge translational research on human muscle ageing across the adult life course.

Advances in our understanding of the biology of skeletal muscle ageing are being made at pace, with great potential for these findings to inform the identification of novel treatments for sarcopenia. However, translation of findings from animal models to humans has been hampered by limitations of existing human muscle biopsy studies. Devised to directly address this challenge, the Muscle Ageing and Sarcopenia Study (MASS) Lifecourse is a novel resource for the study of human muscle ageing. This deep-phenotyped observational study of 260 community-dwelling men and women aged 18 to 85 years living in North East England includes muscle biopsy samples and detailed characterisation of physical function, health status and sociodemographic and behavioural risk factors. Few human observational studies, with muscle tissue sample collection, have the breadth and depth of data on such a wide range of other relevant characteristics across the full adult age range as MASS Lifecourse. This study therefore presents new opportunities to catalyse translational research on ageing muscle across the life course, identify novel treatment targets and deliver benefits for patients and the public.

Human skeletal muscle is a complex, dynamic tissue that changes profoundly with age. It comprises heterogenous cells including long, contractile, multinucleated myofibres, broadly classified into type I (slow-twitch/oxidative) fibres and type II (fast-twitch/glycolytic) fibres, as well as a variety of mononucleated cells (e.g., immune, satellite, and endothelial cells), and the extracellular matrix (ECM). Ageing as well as sarcopenia, a muscle condition characterised by progressive loss of muscle strength and mass observed mostly in older adults, appear to disproportionately affect type II fibres. In histomorphometric studies of ageing muscle this has been described as type II myofibres loss, fibre atrophy, and redistribution of fibre types, although some inconsistent findings exist. The precise mechanisms underlying this selective vulnerability remains elusive but are likely attributable to dysregulated nutrient sensing contributing to the deregulation of muscle protein synthesis and degradation cycle, and neuromuscular junction, satellite cells, ECM and mitochondrial dysfunction. This narrative review focuses on the Vastus Lateralis (VL) muscle—a major limb muscle involved in locomotion and one of the most extensively studied human skeletal muscles— and summarises key structural and phenotypic changes that occur with ageing at the organ, tissue, and cell levels, and their relevance to sarcopenia. We also briefly discuss external influences of these changes, highlight gaps in knowledge, and suggest future directions.

Dietary intake is increasingly recognised as a modifiable determinant of cognitive function, with emerging evidence linking higher intake of ultra-processed foods (UPF) to poorer cognitive outcome, especially in older adults aged 60 and above(1-3). However, evidence on specifically the very old (aged 85 and above) are scarce. Since they are a rapidly growing population in the United Kingdom (UK) where the number of adults aged 85 and over has increased by 186% between 1981 and 2021 (4) . Due to this demographic shift, it is essential to study specifically this populations UPF intake in relation to cognition. The Newcastle 85+ Study (n = 790) provides a unique opportunity to investigate nutritional determinants of cognition in the very old (≥ 85 y); the mean (standard deviation) age at baseline was 85.5 (0.4) y. Baseline diet (2006/07) was assessed with two non-consecutive 24-h recalls (5) and foods were classified according to the NOVA food classification system (6) . Global cognition (Mini-Mental State Examination, MMSE) were assessed at baseline and at 1.5, 3 and 5 years, while the Clinical Dementia Rating (CDR), composite attention scores [Power of Attention (PoA), Continuity of Attention (CoA), Reaction-Time Variability (RTA)] and single-task reaction times [simple reaction time (SRT), choice reaction time (CRT), and vigilance reaction time (VIGRT)] times were assessed at baseline, and at 1.5 and 3 years. UPF intake was categorised into tertiles using the Nova system as a proportion of total energy (%TE). UPF intake supplied 56 % of total energy intake at baseline. Cross-sectionally, higher UPF intake was associated with poorer baseline performance on selected attention and processing-speed measures, but not with global cognition. In fully adjusted regression models, each standard-deviation increase in UPF intake was associated with worse baseline PoA (β = 0.020, SE = 0.010, P = 0.045) and slower baseline SRT (β = 0.049, SE = 0.023, P = 0.032). No statistically significant associations were observed for MMSE, CoA, RTV, CRT, VIGRT, or CDR after full adjustment. Additionally, longitudinal mixed-effects models showed no statistically significant associations between baseline UPF intake and subsequent change in MMSE, attention domains, reaction-time measures, or CDR over up to five years of follow-up. Findings indicate that a higher intake of %TE of UPF was cross-sectionally associated with poorer attention and processing-speed performance, but not global cognition, while longitudinal mixed-effects models showed no association with cognitive decline over three and five years. These findings suggest that associations between UPF intake and cognition may vary within older age groups, highlighting the need to avoid treating adults aged ≥60 years as a homogeneous population and to adopt age-stratified approaches in research on UPF. Further research is needed to confirm whether these observed links reflect a causal influence of high UPF intake on cognition or whether the links are driven by overall diet quality, is essential. Future work should also test how the United Kingdom food-policy initiatives could improve both dietary quality and cognitive health in the very old.

Objectives To estimate the contribution of ultraprocessed foods (UPF) to total energy intake and to macronutrient and micronutrient intakes among very old people aged 85 years in the Newcastle 85+ Study.Design Cross-sectional observational analysis of baseline dietary and demographic data from the Newcastle 85+ cohort.Setting Community-dwelling and institutionalised adults in Newcastle on Tyne and North Tyneside, UK, recruited through general practice registered between June 2006 and October 2007.Participants Eight hundred participants (62% female) aged 85 years at baseline, with two complete non-consecutive 24-hour dietary recalls.Primary outcome The primary outcome was the contribution of UPF (Nova group 4) to total energy intake, macronutrient intakes, expressed as percentage of total energy for carbohydrate, protein, total fat, saturated fat and added sugars, as grams per day for fibre and to micronutrient intakes (vitamins A, B₆, B₁₂, C, D, E and folate) and minerals (calcium, potassium, magnesium, zinc, selenium, phosphorus, iron and sodium). All evaluated across sex, education and socioeconomic status, adjusted tertiles of UPF intake.Results Among the 800 participants included in the analysis, UPF contributed 56% of total energy intake, surpassing that from unprocessed foods (27%). Total energy intake did not differ across tertiles of UPF consumption (lowest vs highest tertile: 1759.5 kcal/day (95% CI 1684.6 to 1834.4) vs 1740.0 kcal/day (1667.3 to 1812.7)). Higher UPF intake was associated with a higher proportion of energy from carbohydrates and added sugars, and a lower proportion from protein and saturated fat. Intakes of several micronutrients were lower in the highest versus the lowest UPF tertile, including vitamin C (59.9 mg/day (49.8 to 70.0) vs 94.0 mg/day (83.7 to 104.4)) and potassium (2455.9 mg/day (2334.1 to 2577.6) vs 2786.3 mg/day (2660.8 to 2911.8)). By contrast, calcium from fortified foods increased across tertiles (6.3 mg/day (3.7 to 8.9) to 15.4 mg/day (12.9 to 17.9)).Conclusions This study highlights the potential role of UPF in the diets of very old people: higher UPF intake was not associated with higher energy intakes often observed in younger populations. Some UPF, particularly fortified products, may contribute to meeting micronutrient requirements in very old people where dietary inadequacies are common. Further research is needed to confirm these findings and to inform dietary guidance for very old people.

Regulatory T cells (Tregs) are important in maintaining tolerance and are key players in immunity. In aging, increased Treg function along with low-grade inflammation has been reported. This dichotomy of enhanced Treg function along with inflammation highlights the importance of understanding Treg biology and communication patterns in the very old. In this proof-of-concept study, we demonstrate that aged Tregs (85 years) do not significantly communicate with CD4+ and CD8+ T effectors when compared with healthy < 66-year-olds. Of note was the enhanced communication of aged Tregs with CD3+CD8+CD56+CD161- NK-like T-cell populations, which are important in antitumor and chronic viral diseases in older individuals. We found that in turn this population of killer-like T cells showed diminished cytotoxic characteristics, and killer receptor expression. Taken together, our proof-of-concept study delineates the biology of Tregs and identifies previously undefined communication patterns in the very old.

Carrot consumption reduces tumour development in several animal models, possibly as sources of polyacetylenes, resistant starch, carotenes or other active constituents. In a recent systematic review and meta-analysis of prospective studies(1), we showed that carrot intake measured directly or using α-carotene as a marker of carrot intake was associated with reduced risk of cancer incidence. However, since the incidence of cancers among very old people (aged 85 and over) is lower than in those aged 65 to 85(2), it is of interest to understand how carrot intake affects cancer risk across different age groups. Here we compare the results from the Newcastle 85+ study3 and a meta-analysis of prospective studies1 of older adults aged 65-85 years at baseline.In the Newcastle 85+ study(3) (n = 387, 65% women), baseline dietary carrot intake was assessed using a multiple-pass recall tool (2×24 h recalls) and α-carotene concentration measured in plasma samples by reverse phase high-performance liquid chromatography. Cancer incidence data were ascertained from medical records, and the association between carrot intake and α-carotene and cancer risk (any type) tested using multivariable Cox proportional hazard regression models. For the meta-analysis(1), mean ± SD of the reported upper age range at baseline in 50 studies (with 52000 cases) with data on carrot intake reported directly or indirectly (as α-carotene intake) was 68 ± 12 years, and in 30 studies (9331 cases) reporting plasma concentration of α-carotene it was 69 ± 9 years.In the Newcastle 85+ study, the summary risk ratio (RR) for cancer incidence was 0.82 (95% CI: 0.24 – 2.79, n = 129 cases, 258 non-cases) for consumption of ≥ 1 vs < 1 serving/day of carrots after adjusting for key confounders. RR for cancer for the highest compared with lowest quartile of plasma α-carotene was 0.68 (0.33 –1.39). The corresponding values comparing highest versus lowest exposure groups for the younger age groups in the meta-analysis(1) were: RRs (95% CI) for carrot intake 0·90 (0·87–0·94) and 0·80 (0·72–0·89) for plasma α-carotene. For most (67 of 80) of the individual studies included in the meta-analysis, the RRs were not statistically significantly different from 1, as was the case for the Newcastle 85+ study, due to small sample size and limited duration of the dietary records. However, the similarity of the RR values from the Newcastle 85+ study with the two corresponding independent datasets in the meta-analysis means that the results do not support a difference in effect between the age groups.The association of carrot consumption with incident cancer in the very old does not differ from younger age groups of older adults. Carrot consumption should be encouraged among the very old, and the causal mechanisms further investigated.

Objectives This study aims to determine whether machine learning can identify specific combinations of long-term conditions (LTC) associated with increased sarcopenia risk and hence address an important evidence gap—people with multiple LTC (MLTC) have increased risk of sarcopenia but it has not yet been established whether this is driven by specific combinations of LTC.Design Decision trees were used to identify combinations of LTC associated with increased sarcopenia risk. Participants were classified as being at risk of sarcopenia based on maximum grip strength of <32 kg for men and <19 kg for women. The combinations identified were triangulated with logistic regression.Setting UK Biobank.Participants UK Biobank participants with MLTC (two or more LTC) at baseline.Results Of 140 001 participants with MLTC (55.3% women, median age 61 years), 21.0% were at risk of sarcopenia. Decision trees identified several LTC combinations associated with an increased risk of sarcopenia. These included drug/alcohol misuse and osteoarthritis, and connective tissue disease and osteoporosis in men, which showed the relative excess risk of interaction of 3.91 (95% CI 1.71 to 7.51) and 2.27 (95% CI 0.02 to 5.91), respectively, in age-adjusted models.Conclusion Knowledge of LTC combinations associated with increased sarcopenia risk could aid the identification of individuals for targeted interventions, recruitment of participants to sarcopenia studies and contribute to the understanding of the aetiology of sarcopenia.

Maximising the potential benefit of resistance exercise (RE) programs by ensuring optimal recovery is an important aim of exercise prescription. Despite this, research surrounding recovery from RE in older adults is limited and inconsistent. The following randomised controlled trial was designed to investigate the efficacy of milk consumption for improving recovery from RE in older adults. However, the study encountered various challenges that may be applicable to similar studies. These include recruitment issues, a lack of measurable perturbations in muscle function following RE, and potential learning effects amongst participants. Various considerations for exercise research have arisen from the data which could inform the design of future studies in this area. These include (i) recruitment—consider ways in which the study design could be altered to aid recruitment or allow a longer recruitment period; (ii) learning effects and familiarisation—consider potential learning effects of outcome measures and adjust familiarisation accordingly; (iii) identify, validate and optimise protocols for outcome measures that are applicable for the specific population; (iv) adjust the exercise protocol according to the specific aims of the study (e.g., are you replicating a usual exercise bout or is the intent to cause large amounts of muscle damage?).

Immunosenescence describes dysregulation of the immune system with ageing manifested in both the innate and adaptive immunity, including changes in T-cell checkpoint signaling. Through complex and nuanced process, T-cells lose excitatory signaling pathways and upregulate their inhibitory signaling, leading to ineffective immune responses that contribute to the formation of the ageing phenotype. Here we expand on the expression, function, and clinical potential of targeting the T-cell checkpoint signaling in age and highlight interventions offering the most benefits to older adults’ health. Notably, modifications in vaccination such as with mTOR inhibitors show immediate clinical relevance and good tolerability. Other proposed treatments, including therapies with monoclonal antibodies fail to show clinical efficacy or tolerability needed for implementation at present. Although T-cell co-signaling fits a valuable niche for translational scientists to manage immunosenescence, future study would benefit from the inclusion of older adults with multiple long-term conditions and polypharmacy, ensuring better applicability to actual patients seen in clinical settings.

Loss of skeletal muscle strength and mass (sarcopenia) is common in older adults and associated with an increased risk of disability, frailty and premature death. Finding cost-effective prevention and treatment strategies for sarcopenia for the growing ageing population is therefore of great public health interest. Although nutrition is considered an important factor in the aetiology of sarcopenia, its potential for sarcopenia prevention and/or treatment is still being evaluated. Nutrition research for sarcopenia utilises three main approaches to understand muscle-nutrition relationships, evaluating: single nutrients, whole foods and whole diet effects - both alone or combined with exercise. Applying these approaches, we summarise recent evidence from qualitative and quantitative syntheses of findings from observational and intervention studies of healthy older adults, and those with sarcopenia. We consider protein supplements, whole foods (fruits and vegetables) and the Mediterranean diet as exemplars. There is some evidence of beneficial effects of protein supplementation ≥ 0·8 g/kg body weight/d on muscle mass when combined with exercise training in intervention studies of healthy and sarcopenic older adults. In contrast, evidence for effects on muscle function (strength and physical performance) is inconclusive. There is reasonably consistent epidemiological evidence suggesting benefits of higher fruits and vegetables consumption for better physical performance. Similarly, higher adherence to the Mediterranean diet is associated with beneficial effects on muscle function in observational studies. However, intervention studies are lacking. This review discusses how current evidence may inform the development of preventive and intervention strategies for optimal muscle ageing and nutritional public policy aimed at combatting sarcopenia.

To investigate cross-sectional and longitudinal associations between glycaemic measures (HbA1c and random glucose) and grip strength (GS) in middle-aged and older adults without prevalent diabetes. A unit increase in HbA1c was associated with 1–3

Background Older adults living with multiple long-term conditions (MLTC, also known as multimorbidity) and frailty are more likely to experience a deterioration in their health requiring specialist referral or hospital admission than individuals without these syndromes. However, this group of older people are underserved by research meaning that there is a limited evidence base for their care. This study therefore aimed 1) to determine if it is feasible to recruit and collect quantitative data to describe the health and lifestyle of older adults living with MLTC, frailty and a recent deterioration in health and 2) to assess if taking part in research is acceptable to this group of older adults. Methods Participants were approached and recruited for this study via an Older People’s Medicine Day Unit in Newcastle upon Tyne, UK. The study took a mixed methods approach, involving quantitative and qualitative data collection. To determine the feasibility of carrying out research in this group, we quantified recruitment rate and collected data on the health and lifestyle, including diet and physical activity, of the participants. Qualitative semi-structured interviews were undertaken to assess acceptability. Two separate interviews were carried out focusing on involving older adults in research and the participants’ experiences of taking part in the research. Interviews were analysed using thematic analysis. Results Fifty patients were approached to participate in the study with twenty-nine (58%) successfully recruited. It was feasible to collect information to describe the health and lifestyle of these older adults who demonstrated very low levels of physical activity. Participants reported that taking part in the research was acceptable to them with interview analysis generating three themes 1) developing a meaningful partnership, 2) enabling factors to participation: research at home with flexible delivery and 3) social and psychological benefits of research participation. Conclusions It is feasible and acceptable to recruit and carry out research with this underserved group of older adults. Participants found taking part in this research to be acceptable and reported overall positive experiences of their involvement in the study and indicated that they would be willing to contribute to further research in the future.

Background Sarcopenia is a skeletal muscle disorder involving accelerated loss of muscle mass and function. Both the presence of two or more long-term conditions, known as multiple long-term conditions (MLTC) or multimorbidity, and specific long-term conditions (LTC), including diabetes and osteoarthritis, are associated with increased risk of sarcopenia. However, it is unclear whether some combinations of LTC are more strongly associated with sarcopenia than others. We aimed to explore this in UK Biobank using decision tree classification techniques. Methods Our analysis included 140,001 UK Biobank participants (55% women) with two or more self-reported LTC at baseline, taken from a list of 53 conditions identified as those which should always or usually be included in MLTC studies. We used grip strength to classify participants as at 'risk of sarcopenia' by applying T-scores of <2 standard deviations below the mean for healthy young adults [<32 kg for men; <19 kg for women]. Decision tree classifiers were then trained on 1000 bootstrap samples of the sex-stratified analytic dataset. We examined the outputs of the decision tree ensembles to identify combinations of conditions most consistently identified with risk of sarcopenia. Odds ratios (OR) of risk of sarcopenia for the highest risk combinations were estimated using logistic regression models, and interactions between LTC explored. Results The decision tree ensembles identified the six highest risk combinations for sarcopenia risk for men as connective tissue disease with any other condition (OR:2.55, 95% CI:2.33–2.80), osteoarthritis with stroke (OR:2.88, CI:2.34–3.54), connective tissue disease with diabetes (OR:3.41, CI:2.66–4.37), diabetes with stroke (OR:2.68, CI:2.30–3.12), diabetes with uncorrectable visual problems (OR:2.33, CI:2.06–2.64), and drug/alcohol misuse with osteoarthritis (OR:4.50, CI:2.73–7.43). For women the combinations identified were multiple sclerosis (MS) with osteoporosis (OR:3.31, CI:1.89–5.78), connective tissue disease with any other condition (OR:2.86, CI:2.70–3.03), chronic obstructive pulmonary disease (COPD) with stroke (OR:3.35, CI:2.50–4.50), coronary artery disease with osteoarthritis (OR:2.43, CI:2.19–2.71), hypertension with MS (OR:2.32, CI:1.80–2.99), and osteoarthritis with osteoporosis (OR:2.42, CI:2.15–2.71). Amongst these combinations, there was some evidence of multiplicative interactions between: osteoarthritis and stroke, diabetes and stroke, diabetes and uncorrectable visual problems, and drug/alcohol misuse and osteoarthritis in men; and COPD and stroke, and hypertension and MS in women. Conclusion We found specific combinations of LTC associated with increased risk of sarcopenia, some of which showed evidence of synergistic effects. Knowledge of these combinations could help to identify individuals for targeted interventions, recruit participants to sarcopenia studies, and contribute to understanding the aetiology of sarcopenia.

Background Many older adults live with the combination of multiple long-term conditions (MLTC) and frailty and are at increased risk of a deterioration in health requiring interaction with healthcare services. Low skeletal muscle strength is observed in individuals living with MLTC and is central to physical frailty. Resistance exercise (RE) is the best available treatment for improving muscle strength, but little is known about the attitudes and barriers to RE in this group of older adults. This study therefore aimed to explore the knowledge of and attitudes towards RE, as well as the barriers and enabling factors, in older adults living with MLTC, frailty and a recent deterioration in health. Methods Fourteen participants aged 69–92 years (10 women) from the Lifestyle in Later Life – Older People’s Medicine (LiLL-OPM) study were recruited from an Older People’s Medicine Day Unit in Newcastle, UK. Participants were invited to take part in a semi-structured interview exploring their knowledge and attitudes as well as barriers and enabling factors to RE. Data were analysed using thematic analysis. Results The analysis generated three themes (1) a lack of awareness and understanding of RE, (2) a self-perceived inability to perform RE; physical and psychological barriers and (3) willingness to perform RE under expert guidance. There was a general lack of awareness and understanding of RE, with most participants having never heard of the term and being unaware of its potential benefits. When RE was described, participants stated that they would be willing to try RE, but it was apparent that an individualised approach underpinned by expert guidance would be required to support engagement. Conclusions Older adults living with MLTC, frailty and a recent deterioration in health lack awareness and understanding of RE. Despite a range of barriers, this group appear willing to engage in RE if they are appropriately supported. There is a need to co-design and deliver effective strategies, including education, to raise awareness and understanding of RE, as well as promote engagement in RE, in this group of older adults.

Cellular senescence may be associated with morphological changes in skeletal muscle and changes in physical function with age although there have been few human studies. We aimed to determine the feasibility of characterising cellular senescence in skeletal muscle and explored sex-specific associations between markers of cellular senescence, muscle morphology, and physical function in participants from the MASS_Lifecourse Study. Senescence markers ( p16 , TAF (Telomere-Associated DNA Damage Foci), HMGB1 (High Mobility Group Box 1), and Lamin B1) and morphological characteristics (fibre size, number, fibrosis, and centrally nucleated fibres) were assessed in muscle biopsies from 40 men and women (age range 47–84) using spatially-resolved methods (immunohistochemistry, immunofluorescence, and RNA and fluorescence in situ hybridisation). The associations between senescence, morphology, and physical function (muscle strength, mass, and physical performance) at different ages were explored. We found that most senescence markers and morphological characteristics were weakly associated with age in men but more strongly, although non-significantly, associated with age in women. Associations between senescence markers, morphology, and physical function were also stronger in women for HMGB1 and grip strength ( r = 0.52); TAF, BMI, and muscle mass ( r > 0.4); Lamin B1 and fibrosis ( r = − 0.5); fibre size and muscle mass ( r ≥ 0.4); and gait speed ( r = − 0.5). However, these associations were non-significant. In conclusion, we have demonstrated that it is feasible to characterise cellular senescence in human skeletal muscle and to explore associations with morphology and physical function in women and men of different ages. The findings require replication in larger studies.

Dietary intake information is key to understanding nutrition-related outcomes. Intake changes with age and some older people are at increased risk of malnutrition. Application, difficulties, and advantages of the 24-hour multiple pass recall (24hr-MPR) dietary assessment method in three cohorts of advanced age in the United Kingdom (UK) and New Zealand (NZ) is described. The Newcastle 85+ study (UK) recruited a single year birth cohort of people aged 85 years during 2006–7. LiLACS NZ recruited a 10-year birth cohort of Māori (indigenous New Zealanders) aged 80–90 years and a single year birth cohort of non-Māori aged 85 years in 2010. Two 24hr-MPR were conducted on non-consecutive days by trained assessors. Pictorial resources and language were adapted for the New Zealand and Māori contexts. Detailed methods are described. In the Newcastle 85+ study, 805 (93%) participants consented to the 24-MPR, 95% of whom completed two 24hr-MPR; in LiLACS NZ, 218 (82%) consented and 203 (76%) Māori and 353 (90%) non-Māori completed two 24hr-MPR. Mean time to complete each 24hr-MPR was 22 minutes in the Newcastle 85+ study, and 45 minutes for Māori and 39 minutes for non-Māori in LiLACS NZ. Dietary assessment of participants residing in residential care and those requiring proxy respondents were successfully included in both studies. Most participants (83–94%) felt that data captured by the 24hr-MPR reflected their usual dietary intake. Dietary assessment using 24hr-MPR was successful in capturing detailed dietary data including information on portion size and time of eating for over 1300 octogenarians in the UK and New Zealand (Māori and non- Māori). The 24hr-MPR is an acceptable method of dietary assessment in this age group.

AbstractMilk is a source of several nutrients which may be beneficial for skeletal muscle. Evidence that links lower milk intake with declines in muscle strength from midlife to old age is lacking. We used data from the Medical Research Council National Survey of Health and Development to test sex-specific associations between milk consumption from age 36 to 60–64 years, low grip strength (GS) or probable sarcopenia, and GS decline from age 53 to 69 years. We included 1340 men and 1383 women with at least one measure of both milk intake and GS. Milk intake was recorded in 5-d food diaries (aged 36, 43, 53 and 60–64 years), and grand mean of total, reduced-fat and full-fat milk each categorised in thirds (T1 (lowest) to T3 (highest), g/d). GS was assessed at ages 53, 60–64, and 69 years, and probable sarcopenia classified at the age of 69 years. We employed logistic regression to examine the odds of probable sarcopenia and multilevel models to investigate decline in GS in relation to milk intake thirds. Compared with T1, only T2 (58·76–145·25 g/d) of reduced-fat milk was associated with lower odds of sex-specific low GS at the age of 69 years (OR (95 % CI): 0·59 (0·37, 0·94), P = 0·03). In multilevel models, only T3 of total milk (≥ 237·52 g/d) was associated with stronger GS in midlife in men (β (95 % CI) = 1·82 (0·18, 3·45) kg, P = 0·03) compared with T1 (≤ 152·0 g/d), but not with GS decline over time. A higher milk intake across adulthood may promote muscle strength in midlife in men. Its role in muscle health in late life needs further examination.

Sarcopenia, the age-related loss of muscle strength and mass or quality, is a common condition with major adverse consequences. Although the pathophysiology is incompletely understood, there are common mechanisms between sarcopenia and the phenomenon of accelerated ageing seen in diabetes mellitus. Drugs currently used to treat type 2 diabetes mellitus may have mechanisms of action that are relevant to the prevention and treatment of sarcopenia, for those with type 2 diabetes and those without diabetes. This review summarises shared pathophysiology between sarcopenia and diabetes mellitus, including the effects of advanced glycation end products, mitochondrial dysfunction, chronic inflammation and changes to the insulin signalling pathway. Cellular and animal models have generated intriguing, albeit mixed, evidence that supports possible beneficial effects on skeletal muscle function for some classes of drugs used to treat diabetes, including metformin and SGLT2 inhibitors. Most human observational and intervention evidence for the effects of these drugs has been derived from populations with type 2 diabetes mellitus, and there is a need for intervention studies for older people with, and at risk of, sarcopenia to further investigate the balance of benefit and risk in these target populations. Not all diabetes treatments will be safe to use in those without diabetes because of variable side effects across classes. However, some agents [including glucagon-like peptide (GLP)-1 receptor agonists and SGLT2 inhibitors] have already demonstrated benefits in populations without diabetes, and it is these agents, along with metformin, that hold out the most promise for further investigation in sarcopenia.

Ageing is a complex biological process associated with increased morbidity and mortality. Nine classic, interdependent hallmarks of ageing have been proposed involving genetic and biochemical pathways that collectively influence ageing trajectories and susceptibility to pathology in humans. Ageing skeletal muscle undergoes profound morphological and physiological changes associated with loss of strength, mass, and function, a condition known as sarcopenia. The aetiology of sarcopenia is complex and whilst research in this area is growing rapidly, there is a relative paucity of human studies, particularly in older women. Here, we evaluate how the nine classic hallmarks of ageing: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication contribute to skeletal muscle ageing and the pathophysiology of sarcopenia. We also highlight five novel hallmarks of particular significance to skeletal muscle ageing: inflammation, neural dysfunction, extracellular matrix dysfunction, reduced vascular perfusion, and ionic dyshomeostasis, and discuss how the classic and novel hallmarks are interconnected. Their clinical relevance and translational potential are also considered.