Mitochondrial oxidative capacity and NAD(+) biosynthesis are reduced in human sarcopenia across ethnicities

Migliavacca, EugeniaTay, Stacey K. H.Patel, Harnish P.Sonntag, TanjaCiviletto, GabrieleMcFarlane, CraigForrester, TerenceBarton, Sheila J.Leow, Melvin K.Antoun, ElieCharpagne, AlineChong, Yap SengDescombes, PatrickFeng, LeiFrancis-Emmanuel, PatriceGarratt, Emma S.Giner, Maria PilarGreen, Curtis O.Karaz, SoniaKothandaraman, NarasimhanMarquis, JulienMetairon, SylvianeMoco, SofiaNelson, GailNgo, SherryPleasants, TonyRaymond, FredericSayer, Avan A.Sim, Chu MingSlater-Jefferies, JoSyddall, Holly E.Tan, Pei FangTitcombe, PhilipVaz, CandidaWestbury, Leo D.Wong, GerardWu, YonghuiCooper, CyrusSheppard, AllanGodfrey, Keith M.Lillycrop, Karen A.Karnani, NeerjaFeige, Jerome N.2020-02-082020-02-082020-02-082019-12-2010.1038/s41467-019-13694-1https://infoscience.epfl.ch/handle/20.500.14299/165209WOS:000509780300012The causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related muscle wasting and weakness termed sarcopenia, which directly impacts physical autonomy and survival. Here, we compare genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 older men from Singapore, Hertfordshire UK and Jamaica. Individuals with sarcopenia reproducibly demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1 alpha/ERR alpha signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced mitochondrial respiratory complex expression and activity, and low NAD(+) levels through perturbed NAD(+) biosynthesis and salvage in sarcopenic muscle. We provide an integrated molecular profile of human sarcopenia across ethnicities, demonstrating a fundamental role of altered mitochondrial metabolism in the pathological loss of skeletal muscle mass and function in older people.Multidisciplinary SciencesScience & Technology - Other Topicshuman skeletal-musclenicotinamide ribosidemolecular signaturemicrorna expressiongene-expressionolder-adultslife-spanstrengthhealthhomeostasisMitochondrial oxidative capacity and NAD(+) biosynthesis are reduced in human sarcopenia across ethnicitiestext::journal::journal article::research article