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BackgroundLower urinary tract symptoms (LUTS) are associated with prevalent frailty and functional impairment, but longitudinal associations remain unexplored.ObjectivesTo assess the association of change in phenotypic frailty with concurrent worsening LUTS severity among older men without clinically significant LUTS at baseline.DesignMulticenter, prospective cohort study.SettingPopulation-based.ParticipantsParticipants included community-dwelling men age ≥65 years at enrollment in the Osteoporotic Fractures in Men study.MeasurementsData were collected at 4 visits over 7 years. Phenotypic frailty score (range: 0-5) was defined at each visit using adapted Fried criterion and men were categorized at baseline as robust (0), pre-frail (1-2), or frail (3-5). Within-person change in frailty was calculated at each visit as the absolute difference in number of criteria met compared to baseline. LUTS severity was defined using the American Urologic Association Symptom Index (AUASI; range: 0-35) and men with AUASI ≥8 at baseline were excluded. Linear mixed effects models were adjusted for demographics, health-behaviors, and comorbidities to quantify the association between within-person change in frailty and AUASI.ResultsAmong 3235 men included in analysis, 48% were robust, 45% were pre-frail, and 7% were frail. Whereas baseline frailty status was not associated with change in LUTS severity, within-person increases in frailty were associated with greater LUTS severity (quadratic P

ObjectivesOur aim was to determine the association between protein intake (overall and by source) and all-cause and cause-specific mortality among older men.DesignProspective cohort study.Setting5790 ambulatory community-dwelling older men from multicenter Osteoporotic Fractures in Men (MrOS) study.MeasurementsTotal energy and protein intake, and protein intake by source (dairy, non-dairy animal, plant) were assessed using a 69-item food frequency questionnaire. We included up to 10-year follow-up with adjudicated cardiovascular, cancer and other mortality outcomes. We used time-to-event analysis with protein exposures, mortality outcome, and adjusted for possible confounders including age, center, education, race, smoking, alcohol use, physical activity, weight, total energy intake (TEI), and comorbidities. Hazard ratios were expressed per each unit=2.9% TEI decrement for all protein intake variables.ResultsThe mean (SD) baseline age of 5790 men was 73.6 (5.8) y. There were 1611 deaths and 211 drop-outs prior to 10 years, and 3868 men who were alive at the 10-year follow-up. The mean (SD) total protein intake was 64.7 (25.8) g/d, while the mean (SD) intake expressed as percent of total energy intake (%TEI) was 16.1 (2.9) %TEI. Lower protein intake was associated with an increased risk of death, with unadjusted HR=1.11 (95% CI: 1.06, 1.17) and adjusted HR=1.09 (95% CI: 1.04, 1.14) and the associations for protein intake by source were similar. The adjusted HR for cancer mortality was HR=1.13 (95% CI: 1.03, 1.25) while the association for CVD mortality was HR=1.08 (95% CI: 0.99, 1.18).ConclusionsLow protein intake, irrespective of source, was associated with a modest increase in risk of all-cause and cause-specific mortality among older men. Special consideration should be given to level of protein intake among older adults.

Dairy protein but not plant protein was associated with bone strength of the radius and tibia in older men. These results are consistent with previous results in women and support similar findings related to fracture outcomes. Bone strength differences were largely due to thickness and area of the bone cortex.IntroductionOur objective was to determine the association of protein intake by source (dairy, non-dairy animal, plant) with bone strength and bone microarchitecture among older men.MethodsWe used data from 1016 men (mean 84.3 years) who attended the Year 14 exam of the Osteoporotic Fractures in Men (MrOS) study, completed a food frequency questionnaire (500-5000 kcal/day), were not taking androgen or androgen agonists, and had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and distal or diaphyseal tibia. Protein was expressed as percentage of total energy intake (TEI); mean ± SD for TEI = 1548 ± 607 kcal/day and for total protein = 16.2 ± 2.9%TEI. We used linear regression with standardized HR-pQCT parameters as dependent variables and adjusted for age, limb length, center, education, race/ethnicity, marital status, smoking, alcohol intake, physical activity level, corticosteroids use, supplement use (calcium and vitamin D), and osteoporosis medications.ResultsHigher dairy protein intake was associated with higher estimated failure load at the distal radius and distal tibia [radius effect size = 0.17 (95% CI 0.07, 0.27), tibia effect size = 0.13 (95% CI 0.03, 0.23)], while higher non-dairy animal protein was associated with higher failure load at only the distal radius. Plant protein intake was not associated with failure load at any site.ConclusionThe association between protein intake and bone strength varied by source of protein. These results support a link between dairy protein intake and skeletal health, but an intervention study is needed to evaluate causality.

UnlabelledVitamin D is hypothesized to suppress inflammation. We tested total and free vitamin D metabolites and their association with inflammatory markers. Interleukin-6 levels were lower with higher 25-hydroxyvitamin D. 1,25-dihydroxyvitamin D and free 25OHD associations mirrored those of 25OHD. However, associations for the two metabolites diverged for tumor necrosis factor alpha (TNF-α) soluble receptors.IntroductionVitamin D is hypothesized to suppress inflammation, and circulating 25-hydroxyvitamin D (25OHD) and inflammatory markers are inversely correlated. However, total serum 25OHD may not be the best indicator of biologically active vitamin D.MethodsWe tested serum total 25OHD, total 1,25(OH)2D, vitamin D binding protein (DBP), and estimated free 25OHD and free 1,25(OH)2D associations with inflammatory markers serum interleukin-6 (IL-6), TNF-α and their soluble receptors, interleukin-10 (IL-10), and C-reactive protein (CRP) as continuous outcomes and the presence of ≥2 inflammatory markers in the highest quartile as a dichotomous outcome, in a random subcohort of 679 men in the Osteoporotic Fractures in Men (MrOS) study.ResultsIL-6 was lower in men with higher 25OHD (-0.23 μg/mL per standard deviation (SD) increase in 25OHD, 95 % confidence intervals (CI) -0.07 to -0.38 μg/mL) and with higher 1,25(OH)2D (-0.20 μg/mL, 95 % CI -0.0004 to -0.39 μg/mL); free D associations were slightly stronger. 25OHD and DBP, but not 1,25(OH)2D, were independently associated with IL-6. TNF-α soluble receptors were inversely associated with 1,25(OH)2D but positively associated with 25OHD, and each had independent effects. The strongest association with ≥2 inflammatory markers in the highest quartile was for free 1,25(OH)2D (odds ratios (OR) 0.70, 95 % CI 0.54 to 0.89 per SD increase in free 1,25(OH)2D).ConclusionsAssociations of 1,25(OH)2D and free 25OHD with IL-6 mirrored those of 25OHD, suggesting that 1,25(OH)2D and free D do not improve upon 25OHD in population-based IL-6 studies. However, associations for the two metabolites diverged for TNF-α soluble receptor, warranting examination of both metabolites in studies of TNF-α and its antagonists.

© 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on

ObjectiveTo assess bone-muscle (B-M) indices as risk factors for incident fractures in men.MethodsParticipants of the Osteoporotic Fractures in Men (MrOS) Study completed a peripheral quantitative computed tomography scan at 66% of their tibial length. Bone macrostructure, estimates of bone strength, and muscle area were computed. Areal bone mineral density (aBMD) and body composition were assessed with dual-energy X-ray absorptiometry. Four year incident non-spine and clinical vertebral fractures were ascertained. B-M indices were expressed as bone-to-muscle ratios for: strength, mass and area. Discriminative power and hazards ratios (HR) for fractures were reported.ResultsIn 1163 men (age: 77.2±5.2 years, body mass index (BMI): 28.0±4.0 kg/m(2), 4.1±0.9 follow-up years, 7.7% of men ⋝1 fracture), B-M indices were smaller in fractured men except for bending and areal indices. Smaller B-M indices were associated with increased fracture risk (HR: 1.30 to 1.74) independent of age and BMI. Strength and mass indices remained significant after accounting for lumbar spine but not total hip aBMD. However, aBMD correlated significantly with B-M indices.ConclusionMass and bending B-M indices are risk factors for fractures in men, but may not improve fracture risk prediction beyond that provided by total hip aBMD.

Background: Osteoporosis is generally thought of as a "woman's disease" because the prevalence of osteoporosis and the rate of fractures are much higher in postmenopausal women than in older men. However, the absolute number of men affected by osteoporosis and fractures is large, as at least 2.8 million men in the United States are thought to have osteoporosis.Questions/purposes: The purposes of this review are to (1) highlight gender differences in osteoporosis and fracture risk, (2) describe disparities in treatment and outcomes after fractures between men and women, and (3) propose solutions to reducing disparities in treatment and prevention.Methods: A literature survey was conducted using MEDLINE with a variety of search terms and using references from the author's personal collection of articles. A formal search strategy and exclusion criteria were not employed and the review is therefore selective. WHERE ARE WE NOW?: Postmenopausal women have a higher prevalence of osteoporosis and greater incidence of fracture than older men. Despite the higher fracture risk in postmenopausal women, older men tend to have worse outcomes after fracture and poorer treatment rates, although less is known about the disease course in men. Multifaceted interventions to improve the screening and treatment for osteoporosis were recently developed. WHERE DO WE NEED TO GO?: Improvement in treatment rates of those at risk, regardless of gender, is an important goal in osteoporosis management. HOW DO WE GET THERE?: Further development and evaluation of cost-effective, multifaceted interventions for screening and treatment of osteoporosis and fractures are needed; such interventions will likely improve the primary prevention of fractures. [ABSTRACT FROM AUTHOR]

This study examined the consistency of the Nottingham power rig in assessing leg extension power in older men, assessed between different examiners with adjustment for the order of measurement (time) and clinic. Fifty-five men (mean, 73 yrs) enrolled in the Osteoporotic Fractures in Men Study had maximum leg extension power of each leg measured at baseline and remeasured 1 wk later. There was a significant effect of time (P < 0.01). The second visit had an average increase in leg extension power (right leg, 14.2 W; left leg, 16.5 W). After accounting for the effect of time, a low coefficient of variation was observed between examiners (right leg 3.49%; left leg 3.46%). Data from the two time points corresponded reasonably well. The effect of time and fatigue should be considered when performing this measurement. The Nottingham power rig provided a reproducible measure of leg extension power in this multisite study of older men. [ABSTRACT FROM AUTHOR]

Background: A standard phenotype of frailty was associated with an increased risk of adverse outcomes including mortality in a recent study of older adults. However, the predictive validity of this phenotype for fracture outcomes and across risk subgroups is uncertain.Methods: To determine whether a standard frailty phenotype was independently associated with risk of adverse health outcomes in older women and to evaluate the consistency of associations across risk subgroups defined by age and body mass index (BMI), we ascertained frailty status in a cohort of 6724 women>or=69 years and followed them prospectively for incident falls, fractures, and mortality. Frailty was defined by the presence of three or more of the following criteria: unintentional weight loss, weakness, self-reported poor energy, slow walking speed, and low physical activity. Incident recurrent falls were defined as at least two falls during the subsequent year. Incident fractures (confirmed with x-ray reports), including hip fractures, and deaths were ascertained during an average of 9 years of follow-up.Results: After controlling for multiple confounders such as age, health status, medical conditions, functional status, depressive symptoms, cognitive function, and bone mineral density, frail women were subsequently at increased risk of recurrent falls (multivariate odds ratio=1.38, 95% confidence interval [CI], 1.02-1.88), hip fracture (multivariate hazards ratio [MHR]=1.40, 95% CI, 1.03-1.90), any nonspine fracture (MHR=1.25, 95% CI, 1.05-1.49), and death (MHR=1.82, 95% CI, 1.56-2.13). The associations between frailty and these outcomes persisted among women>or=80 years. In addition, associations between frailty and an increased risk of falls, fracture, and mortality were consistently observed across categories of BMI, including BMI>or=30 kg/m2.Conclusion: Frailty is an independent predictor of adverse health outcomes in older women, including very elderly women and older obese women. [ABSTRACT FROM AUTHOR]

Background: Prediction of long-term survival in healthy adults requires recognition of features that serve as early indicators of successful aging. The aims of this study were to identify predictors of long-term survival in older women and to develop a multivariable model based upon longitudinal data from the Study of Osteoporotic Fractures (SOF).Methods: We considered only the youngest subjects (n = 4,097) enrolled in the SOF cohort (65 to 69 years of age) and excluded older SOF subjects more likely to exhibit a "frail" phenotype. A total of 377 phenotypic measures were screened to determine which were of most value for prediction of long-term (19-year) survival. Prognostic capacity of individual predictors, and combinations of predictors, was evaluated using a cross-validation criterion with prediction accuracy assessed according to time-specific AUC statistics.Results: Visual contrast sensitivity score was among the top 5 individual predictors relative to all 377 variables evaluated (mean AUC = 0.570). A 13-variable model with strong predictive performance was generated using a forward search strategy (mean AUC = 0.673). Variables within this model included a measure of physical function, smoking and diabetes status, self-reported health, contrast sensitivity, and functional status indices reflecting cumulative number of daily living impairments (HR >or= 0.879 or RH Conclusions: The multivariate model we developed characterizes a "healthy aging" phenotype based upon an integration of measures that together reflect multiple dimensions of an aging adult (65-69 years of age). Age-sensitive components of this model may be of value as biomarkers in human studies that evaluate anti-aging interventions. Our methodology could be applied to data from other longitudinal cohorts to generalize these findings, identify additional predictors of long-term survival, and to further develop the "healthy aging" concept. [ABSTRACT FROM AUTHOR]

Background: This study quantifies incremental healthcare expenditures of functional impairments and phenotypic frailty in specific healthcare sectors., Methods: Pooled 2023 analysis of 4 prospective cohort studies linked with Medicare claims including 4 318 women and 3 847 men attending an index examination (2002-2011). Annualized inpatient, skilled nursing facility (SNF), home healthcare (HHC), and outpatient costs (2023 dollars) ascertained for 36 months following index examination. Functional impairments (difficulty performing 4 activities of daily living) and frailty phenotype (operationalized using 5 components) derived from cohort data. Weighted multimorbidity index including demographics derived from claims., Results: Mean age at index examination was 79.2 years. After accounting for multimorbidity and each other, average annualized incremental costs of 3-4 functional impairments versus no impairment in women (men) were $2 838 ($5 516) in inpatient, $1 572 ($1 446) in SNF, and $1 349 ($1 060) in HHC sectors; average incremental costs of phenotypic frailty versus robust in women (men) was $4 100 (not significant for men) in inpatient, $1 579 ($1 254) in SNF, and $645 ($526) in HHC sectors. Incremental inpatient costs were primarily due to a higher hospitalization risk, while incremental SNF and HHC costs were related to both increased risks of utilization and higher costs among individuals with utilization. Neither geriatric domain was associated with outpatient costs., Conclusions: In this study of community-dwelling beneficiaries, functional impairments were independently associated with higher subsequent expenditures in inpatient, SNF, and HHC sectors among both sexes. Phenotypic frailty was independently associated with higher subsequent inpatient costs in women, and higher SNF and HHC costs in both sexes., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Muscle strength, as measured by handgrip strength (HGS), is associated with physical function and mortality. Yet the environmental context that influences muscle strength is poorly understood. We evaluated built and social neighborhood characteristics and their association with muscle strength over time., Methods: Using data from the Health and Retirement Study (2006-2018), linear mixed models assessed how 11 built and social neighborhood variables were associated with baseline levels and changes in HGS over time., Results: Among the 20 045 respondents (mean age = 63 years, standard deviation = 9.7) with up to 4 HGS measures, 8 455 were men and 11 590 were women. Among men, residing in a neighborhood with a 10% increment higher score on neighborhood disadvantage was associated with a ~1 kg lower HGS at baseline (B = -0.96 kg, 95% confidence interval [CI] = -1.39 to -0.53). Similarly, each 1-point increment on the physical disorder scale was associated with a -0.39 kg lower (95% CI = -0.65 to -0.12) baseline HGS value. Among women, each 10% increment in neighborhood disadvantage was associated with a 0.29 kg lower HGS at baseline (B = -0.29 kg for each 10% increment, 95% CI = -0.46, -0.13). Each 1-unit increment in the number of neighborhood gyms at baseline was associated with a 0.50 kg lower HGS (B = -0.50, 95% CI = -0.76 to -0.23). Each 1-point increment in physical disorder was associated with a -0.12 kg lower (95% CI = -0.24 to -0.00) baseline HGS value. None of the neighborhood features were associated with the HGS rate of change., Conclusions: Findings suggest that residing in neighborhoods with greater disadvantages and physical disorders may pose challenges for HGS among middle-aged adults as they enter into older adulthood., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: Very little is known about specific trajectories or patterns of falls over time. Using the well-characterized cohort of the Osteoporotic Fractures in Men Study (MrOS), we classified individuals by fall trajectories across age and identified predictors of group assignment based on characteristics at baseline., Methods: Using an analysis sample of 5 976 MrOS participants and 15 years of follow-up data on incident falls, we used group-based trajectory models (PROC TRAJ in SAS) to identify trajectories of change. We assessed the association of baseline characteristics with group assignment using 1-way analysis of variance and chi-square tests. Multivariable logistic regression was used to analyze the outcome of the high-risk fall trajectory groups compared to the low-risk groups., Results: Changes in rates of falls were relatively constant or increasing with 5 distinct groups identified. Mean posterior probabilities for all 5 trajectories were similar and consistently above 0.8 indicating a reasonable model fit. Among the 5 fall trajectory groups, 2 were deemed high risk, those with steeply increasing fall risk and persistently high fall risk. Factors associated with fall risk included body mass index, use of central nervous agents, prior history of diabetes and Parkinson's disease, back pain, grip strength, and physical and mental health scores., Conclusions: Two distinct groups of high fall risk individuals were identified among 5 trajectory groups, those with steeply increasing fall risk and persistently high fall risk. Statistically significant characteristics for group assignment suggest that future fall risk of older men may be predictable at baseline., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Greater perceived physical fatigability and lower skeletal muscle energetics are both predictors of mobility decline. Characterizing associations between muscle energetics and perceived fatigability may provide insight into potential targets to prevent mobility decline. We examined associations of in vivo (maximal ATP production, ATPmax) and ex vivo (maximal carbohydrate supported oxidative phosphorylation [max OXPHOS] and maximal fatty acid supported OXPHOS [max FAO OXPHOS]) measures of mitochondrial energetics with two measures of perceived physical fatigability, Pittsburgh Fatigability Scale (PFS, 0-50, higher = greater) and Rating of Perceived Exertion (RPE Fatigability, 6-20, higher = greater) after a slow treadmill walk. Participants from the Study of Muscle, Mobility and Aging (N = 873) were 76.3 ± 5.0 years old, 59.2% women, and 85.3% White. Higher muscle energetics (both in vivo and ex vivo) were associated with lower perceived physical fatigability, all p < 0.03. When stratified by sex, higher ATPmax was associated with lower PFS Physical for men only; higher max OXPHOS and max FAO OXPHOS were associated with lower RPE Fatigability for both sexes. Higher skeletal muscle energetics were associated with 40-55% lower odds of being in the most (PFS ≥ 25, RPE Fatigability ≥ 12) vs least (PFS 0-4, RPE Fatigability 6-7) severe fatigability strata, all p < 0.03. Being a woman was associated with 2-3 times higher odds of being in the most severe fatigability strata when controlling for ATPmax but not the ex vivo measures (p < 0.05). Better mitochondrial energetics were linked to lower fatigability and less severe fatigability in older adults. Findings imply that improving skeletal muscle energetics may mitigate perceived physical fatigability and prolong healthy aging., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Background: A higher difference in estimated glomerular filtration rate by cystatin C versus creatinine (eGFRDiff = eGFRCys - eGFRCreat) is associated with decreased frailty risk. Since eGFRCreat is influenced by muscle more than eGFRCys, muscle mass may explain this association. Previous work could not account for this when considering regional muscle measures by imaging. Deuterated creatine (D 3 Cr) dilution measures whole body muscle mass (kilograms). We aimed to determine whether eGFRDiff is associated with D 3 Cr muscle mass and whether muscle mass explains the association between eGFRDiff and frailty., Methods: Cross-sectional analysis within the multicenter MrOS Study at Year 14 (visit 4). 490 men of the original cohort of 5994 MrOS participants (aged ≥65 at enrollment) were included. Exposure was eGFRDiff (= eGFRCys - eGFRCreat), calculated using CKD-EPI equations 2012/2021. Primary outcome was D 3 Cr muscle mass. Secondary outcome was phenotypic pre-frailty (one or two criteria) and frailty (≥three criteria) including the following: weight loss, weakness, slow gait, physical activity, poor energy. The association of eGFRDiff with D 3 Cr muscle mass was examined by linear regression, that with prefrailty / frailty by multinomial logistic regression., Results: Mean ± SD age was 84 ± 4 years, eGFRCreat 68 ± 16, eGFRCys 52 ± 16, eGFRDiff -15 ± 12 mL/min/1.73 m 2 and D 3 Cr muscle mass 24 ± 4 kg. For each SD increment in eGFRDiff, D3Cr muscle mass was 1.4 kg higher on average, p < 0.0001 (fully adjusted). Higher eGFRDiff was associated with lower odds of frailty (OR = 0.63 95% CI [0.45;0.89]), but this was partially attenuated and insignificant after additionally adjusting for D 3 Cr muscle mass (OR = 0.85 95% CI [0.58; 1.24])., Conclusions: Higher eGFRDiff is associated with lower odds of frailty among late-life men. D 3 Cr muscle mass accounts for some of this association. This suggests that non-GFR determinants of creatinine and cystatin C, such as muscle mass, play a role in explaining the association of eGFRDiff with frailty. Future studies are needed to confirm., (© 2024 The Author(s). Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Physical activity (PA), sedentary behavior (SB), and sleep are each individually associated with falls and fractures, but often are not examined simultaneously. Compositional data analysis examined the combined prospective associations between the proportion of time in PA, SB, and sleep relative to the remaining behaviors with recurrent falls (2+ falls in any year), any fractures, and major osteoporotic fracture (MOF) from tri-annual questionnaires, with adjudication for fractures, in 2918 older men aged 78.9 ± 5.1 years in the Osteoporotic Fractures in Men (MrOS) Study. Accelerometers were worn on the right tricep for seven consecutive 24-hour periods and measured PA (>1.5 METs), SB (≤1.5 METs), and sleep. Generalized Estimating Equations evaluated associations with recurrent falls. Cox proportional hazards regression estimated any incident fracture and MOF risk separately. Over four years of follow-up 1025 (35.2%) experienced recurrent falls; over 10 ± 4 years of follow-up, 669 (22.9%) experienced incident fractures and 370 (12.7%) experienced a MOF. Higher proportions of PA relative to SB and sleep were associated with a lower odds of recurrent falls [Odds Ratio (OR): 0.87, 95% CI: 0.76-0.99]. Higher proportions of SB relative to PA and sleep were associated with a higher odds of recurrent falls (OR: 1.38, 95% CI: 1.06-1.81) and higher risk of any fracture [Hazard Ratio (HR): 1.42, 95% CI: 1.05-1.92]. Higher proportions of sleep relative to PA and SB were associated with a lower risk of fracture (HR: 0.74, 95% CI: 0.54-0.99). No associations of activity composition with MOF were observed. When accounting for the co-dependence of daily activities, higher proportions of SB relative to the proportion of PA and sleep were associated with higher odds of recurrent falls and fracture risk. Results suggest reducing SB (and increasing PA) may lower fall and fracture risk in older men, which could inform future interventions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Sarcopenia is the accelerated loss of skeletal muscle mass and function commonly, but not exclusively, associated with advancing age. It is observed across many species including humans in whom it can lead to decline in physical function and mobility as well as to increased risk of adverse outcomes including falls, fractures and premature mortality. Although prevalence estimates vary because sarcopenia has been defined in different ways, even using a conservative approach, the prevalence is between 5% and 10% in the general population. A life course framework has been proposed for understanding not only the occurrence of sarcopenia in later life but also influences operating at earlier life stages with potentially important implications for preventive strategies. Harnessing progress in understanding the hallmarks of ageing has been key to understanding sarcopenia pathophysiology. Considerable convergence in approaches to diagnosis of sarcopenia has occurred over the last 10 years, with a growing emphasis on the central importance of muscle strength. Resistance exercise is currently the mainstay of treatment; however, it is not suitable for all. Hence, adjunctive and alternative treatments to improve quality of life are needed. An internationally agreed approach to definition and diagnosis will enable a step change in the field and is likely to be available in the near future through the Global Leadership Initiative in Sarcopenia., (© 2024. Springer Nature Limited.)