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Cited by 365Muscle Physiology and DisordersNutrition and Health in AgingMitochondrial Function and Pathology

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

Open access
Migliavacca, Eugenia, Tay, Stacey K. H., Patel, Harnish P., Sonntag, Tanja, Civiletto, Gabriele, McFarlane, Craig, Forrester, Terence, Barton, Sheila J. +35 more·2019·Nature Communications
DOI 10.1038/s41467-019-13694-1PMC PMC6925228
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Abstract

The 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-1α/ERRα 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.

AI snapshot

Written from the paper’s full text.

TL;DR

In a multi-ethnic case-control study of muscle biopsies from older men, sarcopenia was reproducibly characterized by a dominant transcriptional signature of mitochondrial bioenergetic dysfunction, including low PGC-1α/ERRα signaling and downregulated oxidative phosphorylation and mitochondrial proteostasis genes. These changes translated into fewer mitochondria, reduced respiratory complex expression and activity, and 32% lower muscle NAD+ through perturbed NAD+ biosynthesis and salvage.

Key findings

  • In the Singapore Sarcopenia Study (SSS), 179 genes were altered in sarcopenic muscle at FDR < 10% (133 downregulated, 46 upregulated), with 133 genes annotated to the mitochondrion GO term; oxidative phosphorylation, mitochondrial respiratory chain, and TCA cycle gene sets were repressed at FDR < 10E−10, and age-adjusted gene ranks were highly conserved (Spearman rs = 0.95).
  • Mitochondrial dysfunction replicated across ethnicities: HSS and JSS showed lower oxidative phosphorylation, mitochondrial respiratory ETC, and TCA cycle gene sets at FDR < 10E−04 and 10%, respectively; low ALMi and low muscle function also associated with depleted mitochondrial gene sets.
  • Functional validation showed NDUFA9, SDHa, UQCR2, and ATP5a protein levels down by 44–51%, lower complexes I–IV activity, strongly reduced citrate synthase and succinate dehydrogenase activity, and 32% lower muscle NAD+; NAD+ correlated positively with ALMi, grip strength, gait speed, and complex I activity, while NMNAT1 and NAMPT were reduced and CD38, PARPs, and sirtuins were not increased.
  • Other signatures included repressed mTOR signaling (FDR = 1.2E−02) but less than OXPHOS; no denervation/NMJ or inflammatory signatures except weak inflammation in JSS; ALMi associated with 318 genes at FDR < 10%, whereas grip strength and gait speed associated with only 7 and 9 genes at nominal p < 0.001 but FDR > 10%.

Methods

  • Multi-ethnic case-control MEMOSA study of 119 older men from Singapore (SSS), Hertfordshire UK (HSS), and Jamaica (JSS); SSS included 20 sarcopenic Chinese men and 20 age-matched controls, HSS included 40 Caucasian men, and JSS included 40 Afro-Caribbean men. Sarcopenia was defined by AWGSOP (SSS) or EWGSOP (HSS/JSS) criteria using ALMi, grip strength, and gait speed.
  • Vastus lateralis muscle biopsies were profiled by high-coverage total RNA sequencing (>70 million reads per sample; SSS 75–104 million, HSS 51–110 million, JSS 55–88 million); differential expression used limma/edgeR, pathway enrichment used CAMERA with MSigDB, and selected genes were validated by nanoString nCounter.
  • Functional assays included mitochondrial enzymatic activity on mitochondrial fractions from 15–30 mg muscle, western blot for respiratory complex subunits and mitochondrial proteins, and NAD+ quantification in remaining biopsies, benchmarked against UHPLC-MS.

Limitations

  • Stated: NAD+ results require further validation because they were analyzed in a subset of SSS individuals with sufficient remaining muscle biopsy (Fig. 6b, n = 4–6 per group); complex IV western blot was detected in less than 20% of samples and was excluded from analysis.
  • Stated/evident: the cross-sectional case-control design cannot establish causality, and all cohorts were older men, so findings may not generalize to women.
  • Evident: functional validation sample sizes were small and varied by assay and cohort; replication cohorts had variable sample sizes per phenotype (e.g., NAD+ metabolic process gene-set analysis n = 4–28 per group), and no independent prospective validation is reported.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s41467-019-13694-1

Cites

75 of 75 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 24 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Expression profiles of genes controlling mitochondrial dynamics through fusion and fission were lower in sarcopenic individuals.

    “Expression profiles of genes controlling mitochondrial dynamics through fusion and fission were lower in sarcopenic individuals, both through single gene and pathway enrichment analyses (Fig. 2g; Fig. S2d).”
    Quote in the paperSubstantial claim
  • Findingown data

    Many genes controlling the UPRmt were strongly downregulated in muscle of sarcopenic participants, including mitochondrial heat-shock proteins, protease CLPP and transcriptional effectors UBL5, ATF4, and CHOP/DDIT3.

    “Interestingly, many genes controlling the UPRmt were strongly downregulated in the muscle of sarcopenic participants, including those encoding the mitochondrial heat-shock proteins, the protease CLPP and their transcriptional effectors UBL5, ATF4, and CHOP/DDIT3 (Fig. 2i; Supplementary Fig. 2f).”
    Quote in the paperSubstantial claim
  • Findingown data

    Gene sets controlling mitochondrial function were consistently depleted in participants with low ALMi and low muscle function in HSS and JSS cohorts.

    “Gene sets controlling mitochondrial function were also consistently depleted in participants with low ALMi (Fig. 3b) and low muscle function (Fig. 3c) in HSS and JSS cohorts.”
    Quote in the paperSubstantial claim
  • Findingown data

    Mitochondrial respiratory chain, TCA cycle regulator, and oxidative phosphorylation gene sets were repressed in sarcopenic muscle with FDRs < 10E−10.

    “Mitochondrial respiratory chain, TCA cycle regulator, and oxidative phosphorylation gene sets were repressed in sarcopenic muscle with highly significant FDRs (<10E−10).”
    Quote in the paperSubstantial claim
  • Findingown data

    mRNA levels of PGC-1α and ERRα were reduced in sarcopenic muscle.

    “mRNA levels of PGC-1α and ERRα were reduced in sarcopenic muscle (Fig. 2c)”
    Quote in the paperSubstantial claim
  • May combine two claims. 17
  • Classified as probably not a substantial claim. 11

  • May combine two claims.

    Findingown data

    mTOR signaling was repressed in sarcopenic muscle (FDR = 1.2E−02), but to a much lesser extent than oxidative phosphorylation (FDR < 10E−10).

    “As a sign of altered protein anabolism, mTOR signaling was repressed in sarcopenic muscle (FDR = 1.2E−02; Supplementary Fig. 2g), but to a much lesser extent than oxidative phosphorylation (FDR < 10E−10; Supplementary Fig. 1b).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The sarcopenic transcriptional signature was enriched in downregulated genes, with 133 genes annotated under the mitochondrion GO term.

    “This sarcopenic signature was enriched in downregulated genes, out of which 133 genes were annotated under the mitochondrion gene ontology term (Fig. 1b, green ticks).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Gene-set enrichment analysis confirmed mitochondrial bioenergetic dysfunction is a strong signature of sarcopenia in all cohorts/ethnicities, including lower oxidative phosphorylation, mitochondrial respiratory ETC and TCA cycle at FDR < 10E−04 and 10% in HSS and JSS.

    “Gene-set enrichment analysis following high coverage RNA sequencing of sarcopenic and control muscle confirmed that mitochondrial bioenergetic dysfunction is a strong signature of sarcopenia in all cohorts/ethnicities (Fig. 3a), including lower oxidative phosphorylation, mitochondrial respiratory ETC and TCA cycle at FDR < 10E−04 and 10% in HSS and JSS, respectively (Fig. 3a).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    NDUFA9, SDHa, UQCR2, and ATP5a, representing complexes I, II, III, and V, were downregulated by 44-51% in sarcopenic muscle.

    “NDUFA9, SDHa, UQCR2, and ATP5a, representing complexes I, II, III, and V, respectively, were downregulated by 44–51% in sarcopenic muscle (Fig. 5d).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Muscle NAD+ levels correlated positively with ALMi, grip strength, gait speed, and complex I activity.

    “and correlated positively with ALMi, grip strength, gait speed, and complex I activity (Fig. 6c).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Age-adjustment slightly decreased statistical significance of differentially expressed genes but the rank of genes differentially expressed in sarcopenic muscle was highly conserved (Spearman rs = 0.95).

    “Age-adjustment slightly decreased the statistical significance of the differentially expressed genes (Supplementary Fig. 1c), but the rank of genes differentially expressed in sarcopenic muscle was highly conserved (Supplementary Fig. 1d, Spearman rank correlation rs = 0.95).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Independent nanoString nCounter mRNA profiling of 80 selected genes tightly correlated with RNAseq data and confirmed lower expression of mitochondrial function genes in sarcopenic muscle.

    “Independent mRNA gene expression validation of 80 selected genes using nanoString nCounter demonstrated tight correlation with RNAseq data (Supplementary Fig. 1a; Supplementary Data 3), and confirmed lower expression of mitochondrial function genes in sarcopenic muscle (Fig. 1c).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    A large cluster of MRPs was downregulated in sarcopenia and likely contributed to decreased protein expression of mitochondrial respiratory chain subunits.

    “Translational mechanisms also overlapped with this transcriptional regulation as a large cluster of MRPs was downregulated in sarcopenia and likely contributed to the decreased protein expression of mitochondrial respiratory chain subunits.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Reduced NAD+ levels in skeletal muscle of aged or Nampt deficient mice alter mitochondrial bioenergetics and impair muscle mass, strength and endurance.

    “Reduced NAD+ levels in skeletal muscle of aged or Nampt deficient mice alter mitochondrial bioenergetics and impair muscle mass, strength and endurance49,50,52,53”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [49] Camacho-Pereira, J. et al. CD38 dictates age-related NAD Decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell Metab. 23, 1127–1139 (2016). source

      Not checked in the free run.

    • cites [50] Gomes, A. P. et al. Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 155, 1624–1638 (2013). source

      Not checked in the free run.

    • cites [52] Frederick, D. W. et al. Loss of NAD homeostasis leads to progressive and reversible degeneration of skeletal muscle. Cell Metab. 24, 269–282 (2016). source

      Not checked in the free run.

    • cites [53] Zhang, H. et al. NAD(+) repletion improves mitochondrial and stem cell function and enhances life span in mice. Science 352, 1436–1443 (2016). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Human sarcopenia is driven by a major mitochondrial deficit detected both transcriptionally and functionally, for which reduced levels of NAD+ in muscle impair metabolic homeostasis and contribute to functional decline by altering muscle bioenergetics.

    “Thus, human sarcopenia is driven by a major mitochondrial deficit detected both transcriptionally and functionally, for which reduced levels of NAD+ in muscle impair metabolic homeostasis and contribute to functional decline by altering muscle bioenergetics.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Reduced complex activity was linked to lower amounts of mitochondria, as it was not affected when normalized to CS activity.

    “Reduced complex activity was linked to lower amounts of mitochondria as it was not affected when normalized to CS activity (Supplementary Fig. 3b).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    All clinical parameters used to diagnose sarcopenia contribute to the molecular profiles of sarcopenic muscle, with the strongest contribution from low muscle mass followed by grip strength and gait speed.

    “Together, these results demonstrate that all clinical parameters used to diagnose sarcopenia contribute to the molecular profiles of sarcopenic muscle, with the strongest contribution from low muscle mass followed by grip strength and gait speed.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Genetic loss of function of Mfn2 and Opa1 in mice is sufficient to cause sarcopenia.

    “Interestingly, genetic loss of function of Mfn2 and Opa1 in mice is sufficient to cause sarcopenia43–45”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [43] Chen, H. et al. Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations. Cell 141, 280–289 (2010). source

      Not checked in the free run.

    • cites [44] Sebastian, D. et al. Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway. EMBO J. 35, 1677–1693 (2016). source

      Not checked in the free run.

    • cites [45] Tezze, C. et al. Age-associated Loss of OPA1 in muscle impacts muscle mass, metabolic homeostasis, systemic inflammation, and epithelial senescence. Cell Metab. 25, 1374–1389.e6 (2017). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The NAD+ results require further validation as they were analyzed in a subset of individuals with sufficient remaining muscle biopsy from SSS.

    “Although our NAD+ results require further validation as they were analyzed in a subset of individuals with sufficient amounts of remaining muscle biopsy from SSS”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    NAD+ decline during aging is well documented in preclinical models and has recently emerged in humans where skin and brain NAD+ decreases across the lifespan.

    “NAD+ decline during aging is well documented in preclinical models and has recently emerged in humans where skin and brain NAD+ decreases across the lifespan46.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Rajman, L., Chwalek, K. & Sinclair, D. A. Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell Metab. 27, 529–547 (2018). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Sarcopenia arises from a general bioenergetic deficit which differs mechanistically from primary mitochondrial myopathies caused by decreased activity of a specific complex.

    “Thus, sarcopenia arises from a general bioenergetic deficit which differs mechanistically from primary mitochondrial myopathies caused by decreased activity of a specific complex.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationown data

    The MEMOSA study results provide a genome-wide molecular resource of mechanisms and biomarkers of pathological muscle aging across ethnicities.

    “Collectively, the MEMOSA study results provide a genome-wide molecular resource of mechanisms and biomarkers of pathological muscle aging across ethnicities.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Physical activity has established benefits on mitochondrial efficiency in aged skeletal muscle.

    “The established benefits of physical activity on mitochondrial efficiency in aged skeletal muscle2,47,59”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [2] Cartee, G. D., Hepple, R. T., Bamman, M. M. & Zierath, J. R. Exercise promotes healthy aging of skeletal muscle. Cell Metab. 23, 1034–1047 (2016). source

      Not checked in the free run.

    • cites [47] Greggio, C. et al. Enhanced respiratory chain supercomplex formation in response to exercise in human skeletal muscle. Cell Metab. 25, 301–311 (2017). source

      Not checked in the free run.

    • cites [59] Broskey, N. T. et al. Skeletal muscle mitochondria in the elderly: effects of physical fitness and exercise training. J. Clin. Endocrinol. Metab. 99, 1852–1861 (2014). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NAD+ precursor interventions are safe and increase NAD+ levels in early human clinical testing.

    “the demonstration that these interventions are safe and increase NAD+ levels in early human clinical testing46,55,56”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [46] Rajman, L., Chwalek, K. & Sinclair, D. A. Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell Metab. 27, 529–547 (2018). source

      Not checked in the free run.

    • cites [55] Elhassan, Y. S. et al. Nicotinamide riboside augments the aged human skeletal muscle NAD(+) metabolome and induces transcriptomic and anti-inflammatory signatures. Cell Rep. 28, 1717–1728 (2019). e1716. source

      Not checked in the free run.

    • cites [56] Martens, C. R. et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD(+) in healthy middle-aged and older adults. Nat. Commun. 9, 1286 (2018). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    One sample from the SSS cohort was excluded from the analysis because it did not reach the threshold of >35 million uniquely mapped reads due to an abnormally low percentage of uniquely mapped reads.

    “One sample (from the SSS cohort) which did not reach this threshold because of an abnormally low percentage of uniquely mapped reads was excluded from the analysis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    The study creates the mechanistic basis to test the clinical efficacy of NAD+ precursors on muscle strength and physical function in older people with sarcopenia.

    “our study creates the mechanistic basis to test the clinical efficacy of NAD+ precursors on muscle strength and physical function in older people with sarcopenia.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    All RNA samples were homogeneous and passed quality control with 260/280 nm ratio > 1.8 and RIN scores > 7.

    “All RNA samples were homogeneous and passed quality control with 260/280 nm ratio > 1.8 and RIN scores > 7.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Complexes I-III and V were correctly detected in all samples but complex IV was only detected in less than 20% of samples and was excluded from the analysis.

    “Complexes I–III and V were correctly detected in all samples but complex IV was only detected in less than 20% of samples and was excluded from the analysis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    The study provides a strong rationale for intervention trials targeting muscle mitochondrial bioenergetics to manage sarcopenia in older people.

    “provides a strong rationale for intervention trials targeting muscle mitochondrial bioenergetics to manage sarcopenia in older people.”
    Quote in the paperNot a substantial claim
24 of 24

  • The paper relies on this without support.

    Little is known about the molecular processes of pathological sarcopenia compared with healthy muscle aging.

    “While the molecular processes associated with the average functional decline of muscle in the healthy population have been well studied, little is known about the pathological state of sarcopenia, the pathological muscle wasting and weakness of the old age recently assigned an ICD-10 disease code due to its negative impact on physical function, quality of life, and survival6,19–21.”

  • The paper relies on this without support.

    The clinical definition of sarcopenia is standardized enough to characterize a molecular signature of sarcopenia in older people.

    “Standardization of the clinical definition now provides an opportunity to characterize the molecular “signature” of sarcopenia in older people.”
2 of 2

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Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Protein-coding differential gene count differs by one

    Minor

    The Results count 150 protein-encoding genes among the 179 differentially expressed genes, while the Methods describe 149 protein-coding genes differentially regulated in sarcopenia.

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Authors
Migliavacca, E., Tay, S. K. H., Patel, H. P., Sonntag, T., Civiletto, G., McFarlane, C., Forrester, T., Barton, S. J., Leow, M. K., Antoun, E., Charpagne, A., Seng Chong, Y., Descombes, P., Feng, L., Francis-Emmanuel, P., Garratt, E. S., Giner, M. P., Green, C. O., Karaz, S., Kothandaraman, N., Marquis, J., Metairon, S., Moco, S., Nelson, G., Ngo, S., Pleasants, T., Raymond, F., Sayer, A. A., Ming Sim, C., Slater-Jefferies, J., Syddall, H. E., Fang Tan, P., Titcombe, P., Vaz, C., Westbury, L. D., Wong, G., Yonghui, W., Cooper, C., Sheppard, A., Godfrey, K. M., Lillycrop, K. A., Karnani, N., & Feige, J. N.
Affiliations
  • École Polytechnique Fédérale de Lausanne (CH)
  • National University of Singapore (SG)
  • University Hospital Southampton NHS Foundation Trust (GB)
  • James Cook University (AU)
  • University of the West Indies (JM)
  • MRC Lifecourse Epidemiology Unit (GB)
  • Agency for Science, Technology and Research (SG)
  • University of Southampton (GB)
  • University of Auckland (NZ)
  • NIHR Newcastle Biomedical Research Centre (GB)
Corresponding author
  • Godfrey, Keith M.
  • Lillycrop, Karen A.
  • Karnani, Neerja
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-12-20
Volume
10
Issue
1
Pages
5808-5808
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-13694-1
PMC
PMC6925228
OpenAlex
W2992356442
Semantic Scholar
d022163e1837e1b77bb72fbeb26e8415b92d6063
Cited by
365
References
75
Citations by year
2026: 66 · 2025: 74 · 2024: 65 · 2023: 56 · 2022: 50 · 2021: 37 · 2020: 16
FWCI
8.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ResearchOnline at James Cook University (James Cook University) (submittedVersion)
  • ePrints Soton (University of Southampton) (submittedVersion)
  • National University of Singapore (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Funders
  • University Hospital Southampton NHS Foundation Trust
  • National Institute for Health and Care Research (NF-SI-0515-10042, NIHR200286, NF-SI-0508-10082, U24AG047867, 289346, CL-2011-26-002, NF-SI-0617-10109, NF-SI-0513-10085)
  • National Osteoporosis Society
  • University of Southampton
  • University of Oxford
  • European Commission (FP7/2007, 289346)
  • Agency for Science, Technology and Research
  • National University of Singapore
  • Singapore Institute for Clinical Sciences
  • International Osteoporosis Foundation
  • National Institute for Health Research Southampton Biomedical Research Centre (289346)
  • National Institutes of Health
  • Directorate for Biological Sciences
  • Medical Research Council (MC_UU_20/4, MC_UU_12011/4, MC_UU_12011/2, MC_U47585827, MC_UU_12011/1, MC_ST_U2055)
  • Biotechnology and Biological Sciences Research Council (ES/M0099X)
  • Economic and Social Research Council
  • National Institute on Aging (U24AG047867)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
sarcopenia, mitochondrial oxidative capacity, NAD biosynthesis, NAD+ salvage pathway, skeletal muscle aging, oxidative phosphorylation, mitochondrial proteostasis, mitochondrial respiratory chain, mitochondrial mass, ethnic differences, older men
MeSH terms
Proteostasis, Aged, Aged, 80 and over, Aging, Biopsy, Energy Metabolism, United Kingdom, Humans, Jamaica, Male, Middle Aged, Mitochondria, NAD, Oxidation-Reduction, Oxidative Phosphorylation, Singapore, Case-Control Studies, Oxidative Stress, Muscle, Skeletal, Sarcopenia

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