{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T18:41:33Z","timestamp":1793904093324,"version":"4.8.0"},"reference-count":81,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2022-142470OB-I00"],"award-info":[{"award-number":["PID2022-142470OB-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003359","name":"Generalitat Valenciana","doi-asserted-by":"publisher","award":["PROMETEO (CIPROM\/2022\/56)"],"award-info":[{"award-number":["PROMETEO (CIPROM\/2022\/56)"]}],"id":[{"id":"10.13039\/501100003359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CB16\/10\/00435"],"award-info":[{"award-number":["CB16\/10\/00435"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","thelancet.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Lancet Healthy Longevity"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1016\/j.lanhl.2026.100904","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:30:29Z","timestamp":1790623829000},"page":"100904","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sarcopenia as a manifestation of systemic energetic failure with ageing"],"prefix":"10.1016","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6273-1613","authenticated-orcid":false,"given":"Luigi","family":"Ferrucci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0669-1618","authenticated-orcid":false,"given":"Stefano","family":"Donega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9567-6983","authenticated-orcid":false,"given":"Anna","family":"Picca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3760-4118","authenticated-orcid":false,"given":"Miguel","family":"Calvo-Rubio Barrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Rolland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6021-6431","authenticated-orcid":false,"given":"Brian C","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carmen","family":"Gomez-Cabrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"suppl 5","key":"10.1016\/j.lanhl.2026.100904_bib1","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1093\/jn\/127.5.990S","article-title":"Sarcopenia: origins and clinical relevance","volume":"127","author":"Rosenberg","year":"1997","journal-title":"J Nutr"},{"key":"10.1016\/j.lanhl.2026.100904_bib2","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2021.688526","article-title":"Sarcopenia: what is the origin of this aging-induced disorder?","volume":"12","author":"Gustafsson","year":"2021","journal-title":"Front Genet"},{"key":"10.1016\/j.lanhl.2026.100904_bib3","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/S0140-6736(14)62000-6","article-title":"Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study","volume":"386","author":"Leong","year":"2015","journal-title":"Lancet"},{"key":"10.1016\/j.lanhl.2026.100904_bib4","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/ageing\/afy169","article-title":"Sarcopenia: revised European consensus on definition and diagnosis","volume":"48","author":"Cruz-Jentoft","year":"2019","journal-title":"Age Ageing"},{"key":"10.1016\/j.lanhl.2026.100904_bib5","doi-asserted-by":"crossref","DOI":"10.1093\/ageing\/afae052","article-title":"The conceptual definition of sarcopenia: Delphi consensus from the global leadership initiative in sarcopenia (GLIS)","volume":"53","author":"Kirk","year":"2024","journal-title":"Age Ageing"},{"key":"10.1016\/j.lanhl.2026.100904_bib6","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1016\/S0140-6736(19)31138-9","article-title":"Sarcopenia","volume":"393","author":"Cruz-Jentoft","year":"2019","journal-title":"Lancet"},{"key":"10.1016\/j.lanhl.2026.100904_bib7","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/jcsm.12268","article-title":"Pitfalls in the measurement of muscle mass: a need for a reference standard","volume":"9","author":"Buckinx","year":"2018","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"10.1016\/j.lanhl.2026.100904_bib8","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1093\/gerona\/61.10.1059","article-title":"The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study","volume":"61","author":"Goodpaster","year":"2006","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"10.1016\/j.lanhl.2026.100904_bib9","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/jcsm.12494","article-title":"Association of change in muscle mass assessed by D3-creatine dilution with changes in grip strength and walking speed","volume":"11","author":"Duchowny","year":"2020","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"10.1016\/j.lanhl.2026.100904_bib10","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2508286123","article-title":"Mitochondrial remodeling in skeletal muscle underlies exercise-induced reversal of age-associated functional decline in mice and humans","volume":"123","author":"Garc\u00eda-Dom\u00ednguez","year":"2026","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.lanhl.2026.100904_bib11","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1007\/s41999-025-01230-y","article-title":"The association between muscle mass and change in physical functioning in older adults: a systematic review and meta-analysis of prospective studies","volume":"16","author":"Visser","year":"2025","journal-title":"Eur Geriatr Med"},{"key":"10.1016\/j.lanhl.2026.100904_bib12","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1111\/jgs.14927","article-title":"Treatment of sarcopenia with bimagrumab: results from a phase II, randomized, controlled, proof-of-concept study","volume":"65","author":"Rooks","year":"2017","journal-title":"J Am Geriatr Soc"},{"key":"10.1016\/j.lanhl.2026.100904_bib13","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1164\/rccm.201802-0286OC","article-title":"Activin type II receptor blockade for treatment of muscle depletion in chronic obstructive pulmonary disease. A randomized trial","volume":"199","author":"Polkey","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.lanhl.2026.100904_bib14","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/S2213-8587(15)00298-3","article-title":"Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial","volume":"3","author":"Becker","year":"2015","journal-title":"Lancet Diabetes Endocrinol"},{"key":"10.1016\/j.lanhl.2026.100904_bib15","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/ncpendmet0120","article-title":"Drug insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging","volume":"2","author":"Bhasin","year":"2006","journal-title":"Nat Clin Pract Endocrinol Metab"},{"key":"10.1016\/j.lanhl.2026.100904_bib16","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1136\/bjsports-2017-097608","article-title":"A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults","volume":"52","author":"Morton","year":"2018","journal-title":"Br J Sports Med"},{"key":"10.1016\/j.lanhl.2026.100904_bib17","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.jamda.2015.01.071","article-title":"There are no nonresponders to resistance-type exercise training in older men and women","volume":"16","author":"Churchward-Venne","year":"2015","journal-title":"J Am Med Dir Assoc"},{"key":"10.1016\/j.lanhl.2026.100904_bib18","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1249\/MSS.0b013e3181f1bf0d","article-title":"Individual responses to combined endurance and strength training in older adults","volume":"43","author":"Karavirta","year":"2011","journal-title":"Med Sci Sports Exerc"},{"key":"10.1016\/j.lanhl.2026.100904_bib19","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.ejim.2015.10.025","article-title":"Chronic diseases and geriatric syndromes: the different weight of comorbidity","volume":"27","author":"Vetrano","year":"2016","journal-title":"Eur J Intern Med"},{"key":"10.1016\/j.lanhl.2026.100904_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.metabol.2023.155597","article-title":"Current and investigational medications for the treatment of sarcopenia","volume":"149","author":"Rolland","year":"2023","journal-title":"Metabolism"},{"key":"10.1016\/j.lanhl.2026.100904_bib21","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/S0140-6736(12)62167-9","article-title":"Frailty in elderly people","volume":"381","author":"Clegg","year":"2013","journal-title":"Lancet"},{"key":"10.1016\/j.lanhl.2026.100904_bib22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00421-011-1955-7","article-title":"Muscle intracellular oxygenation during exercise: optimization for oxygen transport, metabolism, and adaptive change","volume":"112","author":"Wagner","year":"2012","journal-title":"Eur J Appl Physiol"},{"key":"10.1016\/j.lanhl.2026.100904_bib23","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s13539-014-0154-x","article-title":"Cachexia: a problem of energetic inefficiency","volume":"5","author":"Argil\u00e9s","year":"2014","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"10.1016\/j.lanhl.2026.100904_bib24","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S1470-2045(10)70218-7","article-title":"Definition and classification of cancer cachexia: an international consensus","volume":"12","author":"Fearon","year":"2011","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.lanhl.2026.100904_bib25","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.bone.2015.03.015","article-title":"Inflammation induced loss of skeletal muscle","volume":"80","author":"Londhe","year":"2015","journal-title":"Bone"},{"key":"10.1016\/j.lanhl.2026.100904_bib26","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1093\/ajcn\/71.5.1033","article-title":"Skeletal muscle dysfunction in chronic obstructive pulmonary disease and chronic heart failure: underlying mechanisms and therapy perspectives","volume":"71","author":"Gosker","year":"2000","journal-title":"Am J Clin Nutr"},{"key":"10.1016\/j.lanhl.2026.100904_bib27","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s10741-016-9593-0","article-title":"Skeletal muscle inflammation and atrophy in heart failure","volume":"22","author":"Lavine","year":"2017","journal-title":"Heart Fail Rev"},{"key":"10.1016\/j.lanhl.2026.100904_bib28","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s40520-016-0709-0","article-title":"Nutrition, frailty, and sarcopenia","volume":"29","author":"Cruz-Jentoft","year":"2017","journal-title":"Aging Clin Exp Res"},{"key":"10.1016\/j.lanhl.2026.100904_bib29","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41569-018-0064-2","article-title":"Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty","volume":"15","author":"Ferrucci","year":"2018","journal-title":"Nat Rev Cardiol"},{"key":"10.1016\/j.lanhl.2026.100904_bib30","article-title":"Links between testosterone, oestrogen, and the growth hormone\/insulin-like growth factor axis and resistance exercise muscle adaptations","volume":"11","author":"Gharahdaghi","year":"2020","journal-title":"Front Physiol"},{"key":"10.1016\/j.lanhl.2026.100904_bib31","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1038\/s41591-020-0945-x","article-title":"Antibody-mediated inhibition of GDF15-GFRAL activity reverses cancer cachexia in mice","volume":"26","author":"Suriben","year":"2020","journal-title":"Nat Med"},{"key":"10.1016\/j.lanhl.2026.100904_bib32","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Lopez-Otin","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.lanhl.2026.100904_bib33","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","article-title":"Hallmarks of aging: an expanding universe","volume":"186","author":"L\u00f3pez-Ot\u00edn","year":"2023","journal-title":"Cell"},{"key":"10.1016\/j.lanhl.2026.100904_bib34","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1093\/gerona\/glv202","article-title":"Physical resilience in older adults: systematic review and development of an emerging construct","volume":"71","author":"Whitson","year":"2016","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"10.1016\/j.lanhl.2026.100904_bib35","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1101\/gad.353106.125","article-title":"Mitochondria dysfunction: cause or consequence of physiologic aging?","volume":"39","author":"Budinger","year":"2025","journal-title":"Genes Dev"},{"key":"10.1016\/j.lanhl.2026.100904_bib36","doi-asserted-by":"crossref","DOI":"10.1111\/acel.13942","article-title":"Interactions between mitochondrial dysfunction and other hallmarks of aging: paving a path toward interventions that promote healthy old age","volume":"23","author":"Li","year":"2024","journal-title":"Aging Cell"},{"key":"10.1016\/j.lanhl.2026.100904_bib37","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1093\/gerona\/glv070","article-title":"Reconsidering the role of mitochondria in aging","volume":"70","author":"Gonzalez-Freire","year":"2015","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"10.1016\/j.lanhl.2026.100904_bib38","doi-asserted-by":"crossref","first-page":"4473","DOI":"10.1113\/JP279223","article-title":"August Krogh's theory of muscle microvascular control and oxygen delivery: a paradigm shift based on new data","volume":"598","author":"Poole","year":"2020","journal-title":"J Physiol"},{"key":"10.1016\/j.lanhl.2026.100904_bib39","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1161\/CIRCRESAHA.107.162701","article-title":"Mechanisms of endothelial dysfunction induced by aging: role of arginase I","volume":"101","author":"Katusic","year":"2007","journal-title":"Circ Res"},{"key":"10.1016\/j.lanhl.2026.100904_bib40","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1042\/CS20100476","article-title":"Aging and vascular endothelial function in humans","volume":"120","author":"Seals","year":"2011","journal-title":"Clin Sci (Lond)"},{"key":"10.1016\/j.lanhl.2026.100904_bib41","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2022.980524","article-title":"Does sympathetic vasoconstriction contribute to metabolism: perfusion matching in exercising skeletal muscle?","volume":"13","author":"DeLorey","year":"2022","journal-title":"Front Physiol"},{"key":"10.1016\/j.lanhl.2026.100904_bib42","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1152\/japplphysiol.00113.2018","article-title":"Microvascular mechanisms limiting skeletal muscle blood flow with advancing age","volume":"125","author":"Socha","year":"2018","journal-title":"J Appl Physiol (1985)"},{"key":"10.1016\/j.lanhl.2026.100904_bib43","article-title":"Capillary-mitochondrial oxygen transport in muscle: paradigm shifts","volume":"4","author":"Poole","year":"2023","journal-title":"Function (Oxf)"},{"key":"10.1016\/j.lanhl.2026.100904_bib44","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s00421-021-04854-7","article-title":"Oxygen flux from capillary to mitochondria: integration of contemporary discoveries","volume":"122","author":"Poole","year":"2022","journal-title":"Eur J Appl Physiol"},{"key":"10.1016\/j.lanhl.2026.100904_bib45","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1113\/JP281726","article-title":"Ageing and exercise-induced motor unit remodelling","volume":"600","author":"Jones","year":"2022","journal-title":"J Physiol"},{"key":"10.1016\/j.lanhl.2026.100904_bib46","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1179\/016164104225013806","article-title":"Adaptive and maladaptive motor axonal sprouting in aging and motoneuron disease","volume":"26","author":"Gordon","year":"2004","journal-title":"Neurol Res"},{"key":"10.1016\/j.lanhl.2026.100904_bib47","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/j.devcel.2026.03.010","article-title":"A skeletal muscle atlas shows neuromuscular junction adaptations to growth and atrophy","volume":"61","author":"Campanario","year":"2026","journal-title":"Dev Cell"},{"key":"10.1016\/j.lanhl.2026.100904_bib48","doi-asserted-by":"crossref","DOI":"10.1016\/j.arr.2023.101966","article-title":"Neuromuscular junction transmission failure in aging and sarcopenia: the nexus of the neurological and muscular systems","volume":"89","author":"Arnold","year":"2023","journal-title":"Ageing Res Rev"},{"key":"10.1016\/j.lanhl.2026.100904_bib49","doi-asserted-by":"crossref","DOI":"10.1098\/rsif.2018.0541","article-title":"Metabolic cost underlies task-dependent variations in motor unit recruitment","volume":"15","author":"Lai","year":"2018","journal-title":"J R Soc Interface"},{"issue":"suppl 1","key":"10.1016\/j.lanhl.2026.100904_bib50","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1093\/gerona\/glad029","article-title":"Neural mechanisms of age-related loss of muscle performance and physical function","volume":"78","author":"Clark","year":"2023","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"10.1016\/j.lanhl.2026.100904_bib51","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.freeradbiomed.2024.09.047","article-title":"The repeated bout effect evokes the training-induced skeletal muscle cellular memory","volume":"225","author":"Calvo-Rubio","year":"2024","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.lanhl.2026.100904_bib52","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1016\/j.cmet.2022.10.008","article-title":"Mitochondrial signal transduction","volume":"34","author":"Picard","year":"2022","journal-title":"Cell Metab"},{"key":"10.1016\/j.lanhl.2026.100904_bib53","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1046\/j.1365-201x.2000.00696.x","article-title":"Structural and functional limits for oxygen supply to muscle","volume":"168","author":"Hoppeler","year":"2000","journal-title":"Acta Physiol Scand"},{"key":"10.1016\/j.lanhl.2026.100904_bib54","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/s41586-024-07348-6","article-title":"Multimodal cell atlas of the ageing human skeletal muscle","volume":"629","author":"Lai","year":"2024","journal-title":"Nature"},{"key":"10.1016\/j.lanhl.2026.100904_bib55","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/s42255-023-00783-1","article-title":"Multifaceted mitochondria: moving mitochondrial science beyond function and dysfunction","volume":"5","author":"Monzel","year":"2023","journal-title":"Nat Metab"},{"key":"10.1016\/j.lanhl.2026.100904_bib56","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/s41574-021-00626-7","article-title":"Mitochondrial and metabolic dysfunction in ageing and age-related diseases","volume":"18","author":"Amorim","year":"2022","journal-title":"Nat Rev Endocrinol"},{"key":"10.1016\/j.lanhl.2026.100904_bib57","doi-asserted-by":"crossref","DOI":"10.1111\/acel.13552","article-title":"Muscle mitochondrial energetics predicts mobility decline in well-functioning older adults: the Baltimore longitudinal study of aging","volume":"21","author":"Tian","year":"2022","journal-title":"Aging Cell"},{"key":"10.1016\/j.lanhl.2026.100904_bib58","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/apha.12307","article-title":"Quantification of skeletal muscle mitochondrial function by 31P magnetic resonance spectroscopy techniques: a quantitative review","volume":"213","author":"Kemp","year":"2015","journal-title":"Acta Physiol (Oxf)"},{"key":"10.1016\/j.lanhl.2026.100904_bib59","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.49874","article-title":"Discovery proteomics in aging human skeletal muscle finds change in spliceosome, immunity, proteostasis and mitochondria","volume":"8","author":"Ubaida-Mohien","year":"2019","journal-title":"eLife"},{"key":"10.1016\/j.lanhl.2026.100904_bib60","doi-asserted-by":"crossref","first-page":"4436","DOI":"10.1002\/alz.13388","article-title":"Skeletal muscle mitochondrial function predicts cognitive impairment and is associated with biomarkers of Alzheimer's disease and neurodegeneration","volume":"19","author":"Tian","year":"2023","journal-title":"Alzheimers Dement"},{"key":"10.1016\/j.lanhl.2026.100904_bib61","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-024-55009-z","article-title":"Higher skeletal muscle mitochondrial oxidative capacity is associated with preserved brain structure up to over a decade","volume":"15","author":"Tian","year":"2024","journal-title":"Nat Commun"},{"key":"10.1016\/j.lanhl.2026.100904_bib62","doi-asserted-by":"crossref","DOI":"10.1093\/gerona\/glaf112","article-title":"Mitochondrial bioenergetic profiling in T cell subsets associates with functional health in older adults: a cross-sectional analysis from the INSPIRE-T cohort","volume":"80","author":"Jabrane-Ferrat","year":"2025","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"10.1016\/j.lanhl.2026.100904_bib63","doi-asserted-by":"crossref","DOI":"10.1126\/science.aat5314","article-title":"The integrated stress response: from mechanism to disease","volume":"368","author":"Costa-Mattioli","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.lanhl.2026.100904_bib64","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/s43587-021-00112-9","article-title":"Perspective: modulating the integrated stress response to slow aging and ameliorate age-related pathology","volume":"1","author":"Derisbourg","year":"2021","journal-title":"Nat Aging"},{"key":"10.1016\/j.lanhl.2026.100904_bib65","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41580-019-0101-y","article-title":"The proteostasis network and its decline in ageing","volume":"20","author":"Hipp","year":"2019","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1016\/j.lanhl.2026.100904_bib66","doi-asserted-by":"crossref","DOI":"10.1172\/JCI158448","article-title":"Connecting aging biology and inflammation in the omics era","volume":"132","author":"Walker","year":"2022","journal-title":"J Clin Invest"},{"key":"10.1016\/j.lanhl.2026.100904_bib67","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.3390\/cells13161364","article-title":"Molecular mechanisms of autophagy decline during aging","volume":"13","author":"Lim","year":"2024","journal-title":"Cells"},{"key":"10.1016\/j.lanhl.2026.100904_bib68","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1038\/s42255-025-01411-w","article-title":"Chaperone-mediated autophagy sustains muscle stem cell regenerative functions but declines with age","volume":"7","author":"Ram\u00edrez-Pardo","year":"2025","journal-title":"Nat Metab"},{"key":"10.1016\/j.lanhl.2026.100904_bib69","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/nrd4467","article-title":"Muscle wasting in disease: molecular mechanisms and promising therapies","volume":"14","author":"Cohen","year":"2015","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.lanhl.2026.100904_bib70","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1038\/s41467-023-38410-y","article-title":"Peripheral modulation of antidepressant targets MAO-B and GABAAR by harmol induces mitohormesis and delays aging in preclinical models","volume":"14","author":"Costa-Machado","year":"2023","journal-title":"Nat Commun"},{"key":"10.1016\/j.lanhl.2026.100904_bib71","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/s42255-019-0073-4","article-title":"The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans","volume":"1","author":"Andreux","year":"2019","journal-title":"Nat Metab"},{"key":"10.1016\/j.lanhl.2026.100904_bib72","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2021.44279","article-title":"Effect of urolithin A supplementation on muscle endurance and mitochondrial health in older adults: a randomized clinical trial","volume":"5","author":"Liu","year":"2022","journal-title":"JAMA Netw Open"},{"key":"10.1016\/j.lanhl.2026.100904_bib73","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1038\/s41467-023-36185-w","article-title":"Defective excitation-contraction coupling and mitochondrial respiration precede mitochondrial Ca2+ accumulation in spinobulbar muscular atrophy skeletal muscle","volume":"14","author":"Marchioretti","year":"2023","journal-title":"Nat Commun"},{"key":"10.1016\/j.lanhl.2026.100904_bib74","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ebiom.2017.03.020","article-title":"Mitochondria in cell senescence: is mitophagy the weakest link?","volume":"21","author":"Korolchuk","year":"2017","journal-title":"EbioMedicine"},{"key":"10.1016\/j.lanhl.2026.100904_bib75","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1113\/jphysiol.2007.139477","article-title":"Muscle fatigue: what, why and how it influences muscle function","volume":"586","author":"Enoka","year":"2008","journal-title":"J Physiol"},{"key":"10.1016\/j.lanhl.2026.100904_bib76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1476-5381.2012.01970.x","article-title":"Exercise acts as a drug; the pharmacological benefits of exercise","volume":"167","author":"Vina","year":"2012","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.lanhl.2026.100904_bib77","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1136\/bjsports-2018-100328","article-title":"Precision exercise medicine: understanding exercise response variability","volume":"53","author":"Ross","year":"2019","journal-title":"Br J Sports Med"},{"key":"10.1016\/j.lanhl.2026.100904_bib78","doi-asserted-by":"crossref","DOI":"10.1111\/acel.70026","article-title":"The mitochondria-targeted peptide therapeutic elamipretide improves cardiac and skeletal muscle function during aging without detectable changes in tissue epigenetic or transcriptomic age","volume":"24","author":"Mitchell","year":"2025","journal-title":"Aging Cell"},{"key":"10.1016\/j.lanhl.2026.100904_bib79","article-title":"The effect of SGLT-2 inhibitors on cardiorespiratory fitness capacity: a systematic review and meta-analysis","volume":"13","author":"Peng","year":"2022","journal-title":"Front Physiol"},{"key":"10.1016\/j.lanhl.2026.100904_bib80","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1002\/jcsm.12413","article-title":"Dietary nitrate intake is associated with muscle function in older women","volume":"10","author":"Sim","year":"2019","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"10.1016\/j.lanhl.2026.100904_bib81","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1249\/MSS.0000000000003708","article-title":"BEETter AGING: short-term dietary nitrate supplementation enhances muscle contractile properties in older but not in young adults","volume":"57","author":"Rasica","year":"2025","journal-title":"Med Sci Sports Exerc"}],"container-title":["The Lancet Healthy Longevity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666756826000887?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666756826000887?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:39:09Z","timestamp":1792449549000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2666756826000887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":81,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["S2666756826000887"],"URL":"https:\/\/doi.org\/10.1016\/j.lanhl.2026.100904","relation":{},"ISSN":["2666-7568"],"issn-type":[{"value":"2666-7568","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Sarcopenia as a manifestation of systemic energetic failure with ageing","name":"articletitle","label":"Article Title"},{"value":"The Lancet Healthy Longevity","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.lanhl.2026.100904","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"100904"}}