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Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities
Open accessAbstract
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.
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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.
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26 Own result · 20 Own interpretation · 8 Not checked yet · 6 Own method · 1 Partly supported · 1 No basis given · accuracy not yet measured
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In the paper
“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).”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Perturbed mitochondrial dynamics and UPRmt in sarcopenic muscle
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“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).”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Perturbed mitochondrial dynamics and UPRmt in sarcopenic muscle
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In the paper
“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.”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Sarcopenia has a common transcriptional profile across ethnicities
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In the paper
“Mitochondrial respiratory chain, TCA cycle regulator, and oxidative phosphorylation gene sets were repressed in sarcopenic muscle with highly significant FDRs (<10E−10).”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Mitochondrial dysfunction is the major transcriptional hallmark of sarcopenic muscle
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“mRNA levels of PGC-1α and ERRα were reduced in sarcopenic muscle (Fig. 2c)”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Altered signaling through ERRα and PGC-1α in sarcopenic muscle
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In the paper
“In addition, the promoters of the genes downregulated in sarcopenic muscle were highly enriched in ERRα and nuclear respiratory factor 1 (NRF1) binding sites (Fig. 2e, f).”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Altered signaling through ERRα and PGC-1α in sarcopenic muscle
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In the paper
“Many genes encoding both the small and large subunits of the mitochondrial ribosome were downregulated in sarcopenic muscle (Fig. 2h; Supplementary Fig. 2e)”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Perturbed mitochondrial dynamics and UPRmt in sarcopenic muscle
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“Sets of genes controlling neuromuscular processes, NMJ structure and acetylcholine receptor signaling were not deregulated in sarcopenic muscle across the three cohorts (Supplementary Fig. 2i, k, l)”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Role of other molecular processes in human sarcopenia
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“The pathway enrichment analyses of sarcopenic muscle also revealed lower expression of the transcriptional networks regulated by the ERRα nuclear receptor (gene name ESRRA) and the PGC-1α transcriptional coactivator (PPARGCA1) (Fig. 2a)”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Altered signaling through ERRα and PGC-1α in sarcopenic muscle
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In the paper
“Case–control analysis in SSS revealed a strong perturbation of muscle gene expression in sarcopenic participants where 179 genes encoding 150 proteins and 29 noncoding RNAs were altered in sarcopenic muscle with false-discovery rate (FDR) < 10% (Fig. 1a; Supplementary Data 2).”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Mitochondrial dysfunction is the major transcriptional hallmark of sarcopenic muscle
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In the paper
“Interestingly, genetic loss of function of Mfn2 and Opa1 in mice is sufficient to cause sarcopenia43–45”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Discussion
What the sources say
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
The Results sections report that mice lacking both Mfn1 and Mfn2 in skeletal muscle had smaller muscle fibers and reduced muscle size. OPA1 loss was examined in cells, not mice, and the paper does not establish sarcopenia as the outcome of Mfn2 and Opa1 loss. Page numbers are unavailable in our copy. (LLM, conf=0.88)
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
The Results section reports that Mfn2-deficient mice develop muscle atrophy and that Mfn2 deficiency promotes sarcopenia during aging. The paper describes OPA1’s role in mitochondrial fusion but does not report that loss of Opa1 causes sarcopenia. It also shows age-related sarcopenia is aggravated by Mfn2 loss, rather than establishing that Mfn2 loss alone is sufficient to cause sarcopenia. (LLM, conf=0.88)
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
The Introduction reports that muscle-specific Opa1 deletion causes muscle loss, and the Discussion reports reduced muscle mass after combined Mfn1/Mfn2 deletion. The paper does not establish that loss of Mfn2 alone causes sarcopenia in mice; its mitofusin comparison concerns deletion of both genes. No page numbers are available in our copy. (LLM, conf=0.86)
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In the paper
“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).”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Role of other molecular processes in human sarcopenia
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In the paper
“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).”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Mitochondrial dysfunction is the major transcriptional hallmark of sarcopenic muscle
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In the paper
“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).”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Sarcopenia has a common transcriptional profile across ethnicities
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In the paper
“NDUFA9, SDHa, UQCR2, and ATP5a, representing complexes I, II, III, and V, respectively, were downregulated by 44–51% in sarcopenic muscle (Fig. 5d).”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Mitochondrial bioenergetics is low in human sarcopenic muscle
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In the paper
“and correlated positively with ALMi, grip strength, gait speed, and complex I activity (Fig. 6c).”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > NAD+ levels are low in human sarcopenic muscle
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In the paper
“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).”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Mitochondrial dysfunction is the major transcriptional hallmark of sarcopenic muscle
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In the paper
“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).”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Mitochondrial dysfunction is the major transcriptional hallmark of sarcopenic muscle
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In the paper
“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.”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Discussion
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In the paper
“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”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Discussion
What the sources say
- Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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
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In the paper
“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.”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > NAD+ levels are low in human sarcopenic muscle
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In the paper
“Reduced complex activity was linked to lower amounts of mitochondria as it was not affected when normalized to CS activity (Supplementary Fig. 3b).”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Mitochondrial bioenergetics is low in human sarcopenic muscle
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In the paper
“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.”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Muscle mass and strength drive the molecular phenotype of sarcopenia
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In the paper
“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”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Discussion
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In the paper
“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.”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Discussion
What the sources say
- Not checked yetcites [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
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In the paper
“Thus, sarcopenia arises from a general bioenergetic deficit which differs mechanistically from primary mitochondrial myopathies caused by decreased activity of a specific complex.”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Mitochondrial bioenergetics is low in human sarcopenic muscle
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In the paper
“Collectively, the MEMOSA study results provide a genome-wide molecular resource of mechanisms and biomarkers of pathological muscle aging across ethnicities.”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Discussion
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In the paper
“The established benefits of physical activity on mitochondrial efficiency in aged skeletal muscle2,47,59”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Discussion
What the sources say
- Not checked yetcites [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 yetcites [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 yetcites [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
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In the paper
“the demonstration that these interventions are safe and increase NAD+ levels in early human clinical testing46,55,56”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Discussion
What the sources say
- Not checked yetcites [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 yetcites [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 yetcites [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
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In the paper
“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.”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Methods > mRNA differential expression & pathway enrichment analyses
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In the paper
“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.”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Discussion
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Probably not a substantial claim. It may be too vague to check against evidence.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All RNA samples were homogeneous and passed quality control with 260/280 nm ratio > 1.8 and RIN scores > 7.”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Methods > RNA extraction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Methods > Western blot
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“provides a strong rationale for intervention trials targeting muscle mitochondrial bioenergetics to manage sarcopenia in older people.”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Discussion
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
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.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Mitochondrial dysfunction and low nicotinamide adenine dinucleotide (NAD+) levels are hallmarks of skeletal muscle ageing and sarcopenia1–3”
From Trigonelline Is an NAD+ Precursor That Improves Muscle Function during Ageing and Is Reduced in Human Sarcopenia (2024) · cites this paper as [3]
Experimental — accuracy not yet measuredIn the citing paper
“Our previous profiling of muscle biopsies from patients with sarcopenia versus age-matched healthy controls revealed that mitochondrial dysfunction and reduced NAD+, two well-established molecular hallmarks of organismal ageing11, are prominent features of pathological progression and sarcopenia3.”
From Trigonelline Is an NAD+ Precursor That Improves Muscle Function during Ageing and Is Reduced in Human Sarcopenia (2024) · cites this paper as [3]
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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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Results > Mitochondrial dysfunction is the major transcriptional hallmark of sarcopenic muscle
“179 genes encoding 150 proteins and 29 noncoding RNAs were altered in sarcopenic muscle”
§ Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities > Methods > Network and gene ontology analyses
“Protein interaction networks were generated with the 149 protein coding genes differentially regulated in sarcopenia”
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Sarcopenia definition, diagnosis and treatment: consensus is growing
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Molecular Mechanisms of Inflammation in Sarcopenia: Diagnosis and Therapeutic Update
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“As aforementioned, NAD biosynthesis is reduced in skeletal muscle from Caucasian, African, and Asian sarcopenic cohorts [35].”
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Self-citationSarcopenia and Cognitive Function: Role of Myokines in Muscle Brain Cross-Talk
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BackgroundThe role of NAD+ metabolism and its modulation of mitochondria in aging and disease
Yusri, K., Jose, S., Vermeulen, K. S., Tan, T. C. M., & Sorrentino, V. (2025) · npj Metabolic Health and Disease · doi:10.1038/s44324-025-00067-0 · Cited by 194
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InfluentialMuscle Wasting and Sarcopenia in Heart Failure—The Current State of Science
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Self-citationExercise and mitochondrial mechanisms in patients with sarcopenia
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Impact of Adipose Tissue and Lipids on Skeletal Muscle in Sarcopenia
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“Furthermore, human sarco-penic muscle showed reduced expression of genes regulating mitochondrial unfolded protein response (UPRmt), whose function is a repair or salvage of dysfunctional mitochondria [47].”
NAD+ repletion with niacin counteracts cancer cachexia
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“In a recent multi-ethnic study (MEMOSA—Multi-Ethnic Molecular determinants of Sarcopenia) involving participants from Singapore, the UK, and Jamaica [9], the genome-wide transcriptomic profiles of skeletal muscle biopsies in 119 older men diagnosed with sarcopenia compared with age-matched controls were examined using…”
MethodBrain-muscle communication prevents muscle aging by maintaining daily physiology
Kumar, A., Vaca-Dempere, M., Mortimer, T., Deryagin, O., Smith, J. G., Petrus, P., Koronowski, K. B., Greco, C. M., Segalés, J., Andrés, E., et al. (2024) · Science · doi:10.1126/science.adj8533 · Cited by 72
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“These data were also supported by a recent study in humans, which showed that sarcopenia is associated with altered expression of genes regulating mitochondrial energy production in skeletal muscle (Migliavacca et al., 2019).”
BackgroundResultHosoda, R., Nakashima, R., Yano, M., Iwahara, N., Asakura, S., Nojima, I., Saga, Y., Kunimoto, R., Horio, Y., & Kuno, A. (2023) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2023.04.001 · Cited by 77
Basse, A. L., Agerholm, M., Farup, J., Dalbram, E., Nielsen, J., Ørtenblad, N., Altıntaş, A., Ehrlich, A. M., Krag, T. O. B., Bruzzone, S., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101271 · Cited by 61
“NAMPT and NADþ levels were previously found to be decreased in muscle from a small number of individuals with sarcopenia [68].”
BackgroundReactive oxygen species in the pathogenesis of sarcopenia
Xu, H., Brown, J. L., Bhaskaran, S., & Van Remmen, H. (2025) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2024.11.046 · Cited by 61
“Patients experiencing sarcopenia have reduced expression and activity of mitochondrial respiratory complexes and downregulated oxidative phosphorylation and mitochondrial protein homeostasis genes in skeletal muscle when compared to patients without sarcopenia [74].”
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Neuromuscular impairment at different stages of human sarcopenia
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“…with recent data showing that gene sets involved in NMJ regulation were not altered in sarcopenic compared with non-sarcopenic individuals of different ethnicities, 29 although a caveat of that study is that it used bulk RNA-Seq and did not assess the signalling from single subsynaptic myonuclei.”
BackgroundMitochondrial Quality Control in Sarcopenia: Updated Overview of Mechanisms and Interventions
Liu, D., Fan, Y., Tao, X., Pan, W., Wu, Y., Wang, X., He, Y., Xiao, W., & Li, Y. (2021) · Aging and Disease · doi:10.14336/ad.2021.0427 · Cited by 62
“Notably, three prominent metabolic regulators (AMPK, PGC-1α and SIRT1) apparently cooperate to hinder the progression of sarcopenia.”
BackgroundInfluentialAutophagy in sarcopenia: Possible mechanisms and novel therapies
Xie, G., Jin, H., Mikhail, H., Pavel, V., Yang, G., Ji, B., Lu, B., & Li, Y. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115147 · Cited by 62
Sarcopenia in aging, obesity, and cancer
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“By preserving NAD+ pools, PARP inhibitors, commonly used in chemotherapy, can improve mitochondrial metabolism, which may preserve muscle mass (34-40).”
BackgroundGDF‐15 is associated with sarcopenia and frailty in acutely admitted older medical patients
Kamper, R. S., Nygaard, H. H., Praeger‐Jahnsen, L., Ekmann, A., Ditlev, S. B., Schultz, M., Hansen, S. K., Hansen, P., Pressel, E., & Suetta, C. (2024) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13513 · Cited by 55
Evidence of superconducting Fermi arcs
Kuibarov, A., Suvorov, O., Vocaturo, R., Fedorov, A. V., Lou, R., Merkwitz, L., Voroshnin, V. Y., Facio, J. I., Koepernik, K., Yaresko, A. N., et al. (2024) · Nature · doi:10.1038/s41586-023-06977-7 · Cited by 58
SIRT1 signaling pathways in sarcopenia: Novel mechanisms and potential therapeutic targets
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Standpoints in mitochondrial dysfunction: Underlying mechanisms in search of therapeutic strategies
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Impaired age-associated mitochondrial translation is mitigated by exercise and PGC-1α
de Smalen, L. M., Börsch, A., Leuchtmann, A. B., Gill, J. F., Ritz, D., Zavolan, M., & Handschin, C. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2302360120 · Cited by 46
“Given that we and others (35) did not observe any upregulation of UPR mt markers in sarcopenic muscle, it is unlikely that the reduced translation rates that we observed are caused by this mechanism.”
BackgroundInfluentialNunes-Pinto, M., de Mello, R. G. B., Pinto, M. N., Moro, C., Vellas, B. J., Martinez, L. O., Rolland, Y., & Barreto, P. D. S. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102587 · Cited by 52
Endoplasmic reticulum stress in human chronic wound healing: Rescue by 4‐phenylbutyrate
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“Seattle, WA) to measure the gene expression levels of candidate genes, as previously described.(47)”
MethodShavlakadze, T., Xiong, K., Mishra, S., McEwen, C., Gadi, A., Wakai, M., Salmon, H. A., Stec, M. J., Negron, N., Ni, M., et al. (2023) · Skeletal Muscle · doi:10.1186/s13395-023-00321-3 · Cited by 48
Muscle aging and sarcopenia: The pathology, etiology, and most promising therapeutic targets
Grima-Terrén, M., Campanario, S., Ramírez‐Pardo, I., Cisneros, A., Hong, X., Perdiguero, E., Serrano, A. L., Isern, J., & Muñoz‐Cánoves, P. (2024) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2024.101319 · Cited by 52
Antoun, E., Garratt, E. S., Taddei, A., Burton, M. A., Barton, S. J., Titcombe, P., Westbury, L. D., Baczynska, A., Migliavacca, E., Feige, J. N., et al. (2021) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12876 · Cited by 47
“RNA was extracted from frozen muscle tissue using the mirVana miRNA Isolation Kit (Ambion, Life Technologies), and RNA sequencing carried out as described in Migliavacca et al.(17)”
InfluentialSelf-citationNAD+ Precursors: A Questionable Redundancy
Cantó, C. (2022) · Metabolites · doi:10.3390/metabo12070630 · Cited by 41
Nicotinamide Adenine Dinucleotide in Aging Biology: Potential Applications and Many Unknowns
Bhasin, S., Seals, D. R., Migaud, M. E., Musi, N., & Baur, J. A. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad019 · Cited by 50
Dozio, E., Vettoretti, S., Lungarella, G., Messa, P., & Romanelli, M. M. C. (2021) · Biomedicines · doi:10.3390/biomedicines9040405 · Cited by 45
“Worth noting is the observation that one molecular signature of the transition between healthy to sarcopenic muscle is low mitochondrial bioenergetic capacity [54].”
BackgroundKim, J., Lee, J.-Y., & Kim, C. Y. (2023) · Nutrients · doi:10.3390/nu15112625 · Cited by 45
“In a human biopsy study, the protein expression levels of mitochondrial fusion factor Mfn2 were revealed to be significantly reduced in older individuals with sarcopenia than those in control individuals [75].”
BackgroundFrom mitochondria to sarcopenia: Role of inflammaging and RAGE-ligand axis implication
Daussin, F., Boulanger, É., & Lancel, S. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2021.111247 · Cited by 42
The Role of Mitochondria in Mediation of Skeletal Muscle Repair
Alway, S. E., Paez, H. G., & Pitzer, C. R. (2023) · Muscles · doi:10.3390/muscles2020011 · Cited by 48
Identification of a KLF5-dependent program and drug development for skeletal muscle atrophy
Liu, L., Koike, H., Ono, T., Hayashi, S., Kudo, F., Kaneda, A., Kagechika, H., Manabe, I., Nakashima, T., & Oishi, Y. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2102895118 · Cited by 42
“GSE111017 contained data from three cohorts.”
InfluentialKameda, M., Teruya, T., Yanagida, M., & Kondoh, H. (2021) · Aging · doi:10.18632/aging.203498 · Cited by 40
“Consistently, recent comparative RNA analysis in muscle biopsy also identified mitochondrial dysfunction in sarcopenia [52].”
BackgroundAging and putative frailty biomarkers are altered by spaceflight
Camera, A., Tabetah, M., Castañeda, V., Kim, J., Galsinh, A. S., Haro-Vinueza, A., Salinas, I., Seylani, A., Arif, S., Das, S., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-57948-5 · Cited by 43
“…from 118 people with and without sarcopenia (GSE111006, GSE111010, and GSE111016) 27 , 6,892 DEGs were identified by performing Mann–Whitney U tests 28 on gene expression data for every single gene (i.e., 65,217 genes) in a pair-wise manner across samples from both sets of patients (Supplementary…”
MethodZeng, H., Xu, J., Wang, X., Li, S., & Han, Z. (2022) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2022.113441 · Cited by 39
NAD+ centric mechanisms and molecular determinants of skeletal muscle disease and aging
Wagner, S., Manickam, R., Brotto, M. A. P., & Tipparaju, S. M. (2022) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-022-04408-1 · Cited by 39
“Further investigation demonstrated a significant decrease in many mitochondrial genes, including those forming the electron transport chain, Complex I–V in the sarcopenia muscle biopsies [73].”
BackgroundShero, J. A., Lindholm, M. E., Sandri, M. F., & Stanford, K. I. (2025) · Circulation Research · doi:10.1161/circresaha.124.325614 · Cited by 45
Physiological Systems in Promoting Frailty
Perazza, L. R., Brown‐Borg, H. M., & Thompson, L. V. (2022) · Comprehensive physiology · doi:10.1002/cphy.c210034 · Cited by 69
A transition to degeneration triggered by oxidative stress in degenerative disorders
Stern, M., & McNew, J. A. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-00943-9 · Cited by 33
Mitochondrial mechanisms in the pathogenesis of chronic inflammatory musculoskeletal disorders
Wu, K., Shieh, J.-S., Qin, L., & Guo, J. J. (2024) · Cell & Bioscience · doi:10.1186/s13578-024-01259-9 · Cited by 39
Romani, M., Berger, M. M., & D’Amelio, P. (2022) · Nutrients · doi:10.3390/nu14030483 · Cited by 34
“Mitochondrial potential and transport, two altered features of sarcopenic muscles, are essential for mitochondrial quality control mechanisms; hence, UPRmt and mitophagy are altered during pathological muscle aging [53,54] (Figure 2).”
BackgroundMakhnovskii, P. A., Bokov, R. O., Kolpakov, F., & Popov, D. V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031208 · Cited by 32
“Notably, a previous study found that the same number of genes encoding mitochondrial proteins were expressed at lower levels in sarcopenic human VL muscle showing low mitochondrial density than in age-matched controls [70].”
ResultMeng, L., Yang, R., Wang, D., Wu, W., Shi, J. C., Shen, J., Dang, Y.-M., Fan, G., Shi, H., Dong, J., et al. (2022) · BMC Geriatrics · doi:10.1186/s12877-022-02953-4 · Cited by 32
“The results provided an integrated molecular profile of human sarcopenia across ethnicities, demonstrating a fundamental role of altered mitochondrial metabolism in the pathological losses of skeletal muscle mass and function in older people [60].”
BackgroundAssociation of plasma mitochondrial DNA with COPD severity and progression in the SPIROMICS cohort
Zhang, W. Z., Hoffman, K. L., Schiffer, K. T., Oromendia, C., Rice, M. C., Barjaktarević, I., Peters, S. P., Putcha, N., Bowler, R. P., Wells, J. M., et al. (2021) · Respiratory Research · doi:10.1186/s12931-021-01707-x · Cited by 29
“grip strength), phenotypes which are commonly observed in patients with severe COPD and which may be attributable to mitochondrial dysfunction [47, 48].”
BackgroundParathyroid hormone-related peptide.
Kaiser, S. M., & Goltzman, D. (1993) · PubMed · Cited by 30
Jeong, I., Cho, E., Yook, J.-S., Choi, Y., Park, D., Kang, J., Lee, S.-H., Seo, D. Y., Jung, S., & Kwak, H. (2024) · Life · doi:10.3390/life14080962 · Cited by 35
“…adults with sarcopenia, skeletal muscle mitochondria demonstrate a characteristic decline in the expression and activity of mitochondrial respiratory complexes, accompanied by suppressed oxidative phosphorylation and downregulation of genes responsible for mitochondrial protein quality control [9].”
BackgroundXu, J., Wakai, M., Xiong, K., Yang, Y., Prabakaran, A., Wu, S. P., Ahrens, D., Molina‐Portela, M. D. P., Ni, M., Bai, Y., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115403 · Cited by 35
Implications of NAD + boosters in translational medicine
Kang, B. E., Choi, J., Stein, S., & Ryu, D. (2020) · European Journal of Clinical Investigation · doi:10.1111/eci.13334 · Cited by 32
Ginseng and ginsenosides: Therapeutic potential for sarcopenia
Zha, W., Sun, Y., Gong, W., Li, L., Kim, W., & Li, H. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113876 · Cited by 31
Relevance of endoplasmic reticulum and mitochondria interactions in age-associated diseases
Gil-Hernández, A., & Silva‐Palacios, A. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101193 · Cited by 30
Mau, T., Barnes, H. N., BLACKWELL, T. L., Kramer, P. A., Bauer, S. R., Marcinek, D. J., Ramos, S. V., Forman, D. E., Toledo, F. G. S., Hepple, R. T., et al. (2023) · GeroScience · doi:10.1007/s11357-023-01002-1 · Cited by 27
“2 and 3 Discussion Frailty may stem from individuals having diminished or scarcer energy reserves in musculoskeletal systems [8, 33, 34], where some older adults could become frail sooner due to an accelerated onset of muscle and physical decline.”
Mishra, S., Welch, N., Karthikeyan, M., Bellar, A., Musich, R. J., Singh, S. S., Zhang, D., Sekar, J., Attaway, A. H., Chelluboyina, A. K., et al. (2023) · Aging Cell · doi:10.1111/acel.13852 · Cited by 28
FOXO-regulated DEAF1 controls muscle regeneration through autophagy
Goh, K. Y., Lee, W. X., Choy, S. M., Priyadarshini, G. K., Chua, K., Tan, Q. H., Low, S. Y., Chin, H. S., Wong, C. S., Huang, S., et al. (2024) · Autophagy · doi:10.1080/15548627.2024.2374693 · Cited by 33
“RNA-seq data investigating sarcopenia in human patients was downloaded from GEO (GSE111010 and GSE111016) [71].”
Targeting Mitochondria to Control Ageing and Senescence
Protasoni, M., & Serrano, M. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020352 · Cited by 30
Vintila, A. R., Slade, L., Cooke, M., Willis, C. R. G., Torregrossa, R., Rahman, M., Anupom, T., Vanapalli, S. A., Gaffney, C. J., Gharahdaghi, N., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2216141120 · Cited by 25
“Conversely, sarcopenia associates with postdevelopmental FoxO upregulation across species (58), corresponding with later life metabolic reprogramming to compensate for aging health decline (57, 58).”
Wang, Y., Li, J., Zhang, Z., Wang, R., Hai, B., & Zhang, Y. (2023) · Life · doi:10.3390/life13041006 · Cited by 29
“In skeletal muscle from aging mice, the levels of UPRmt proteins are reduced, and in muscle biopsy samples from sarcopenic humans, the expression of UPRmt genes is decreased, indicating an insufficient UPRmt response to repair or neutralize oxidative stress-induced damage to mitochondrial proteins [82,83].”
BackgroundSong, L., Xue, J., Xu, L., Cheng, L., Zhang, Y., & Wang, X. (2024) · Experimental Gerontology · doi:10.1016/j.exger.2024.112468 · Cited by 28
“Many studies have shown that PGC-1 α degradation is closely associated with mitochondrial dysfunction in aged sarcopenia (Migliavacca et al., 2019; Ji and Kang, 2015; Fern ´ andez-L ´ azaro et al., 2022; Derbr ´ e et al., 2012).”
BackgroundExercise reduces intramuscular stress and counteracts muscle weakness in mice with breast cancer
Mader, T., Chaillou, T., Alves, E. S., Jude, B., Cheng, A. J., Kenne, E. M., Mijwel, S., Kurzejamska, E., Vincent, C. T., Rundqvist, H., et al. (2022) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12944 · Cited by 25
“Reduced mitochondrial function and mitochondrial damage is linked to reduced muscle function and muscle weakness.(13,20,21) Moreover, recent transcriptomics and proteomics analyses showed that mitochondrial ETC genes and proteins were lower in skeletal muscle from breast cancer patients than healthy controls.”
BackgroundPulse Wave Velocity and Sarcopenia in Older Persons—A Systematic Review and Meta-Analysis
Piotrowicz, K., Klich‐Rączka, A., Skalska, A., Gryglewska, B., Grodzicki, T. K., & Gąsowski, J. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19116477 · Cited by 26
Wu, W., Yuan, S., Tang, Y., Meng, X., Peng, M., Hu, Z., & Liu, W. (2023) · Nutrients · doi:10.3390/nu15132851 · Cited by 33
Artificial‐intelligence‐driven discovery of prognostic biomarker for sarcopenia
Chung, H., Jo, Y., Ryu, D., Jeong, C., Choe, S., & Lee, J. (2021) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12840 · Cited by 25
“Sarcopenia is often associated with physical frailty,(23) reduced muscle function,(27) and mitochondrial dysfunction.(14) In addition, recent studies revealed that amyloidosis in skeletal muscle is associated with mitochondrial dysfunction(28,29) and muscle diseases including inclusion body myositis,(30,31) indicating…”
InfluentialNAD depletion in skeletal muscle does not compromise muscle function or accelerate aging
Chubanava, S., Karavaeva, I. E., Ehrlich, A. M., Justicia, R. M., Basse, A. L., Kulik, I., Dalbram, E., Ahwazi, D., Heaselgrave, S. R., Trôst, K., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.04.002 · Cited by 30
Bae, J., Jo, A., Cho, S. C., Lee, Y., Kam, T., You, C.-L., Jeong, H., Kim, H., Jeong, M., Jeong, Y., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.abh3489 · Cited by 23
Aging-Related Sarcopenia: Metabolic Characteristics and Therapeutic Strategies
Chen, Y., & Wu, J. (2024) · Aging and Disease · doi:10.14336/ad.2024.0407 · Cited by 24
“Not only that, but several studies have also indicated an age-related decline in both the quantity and functionality of mitochondria in skeletal muscle [130-133].”
New insights into healthy ageing, inflammageing and frailty using metabolomics
Abdullah, G. A., Akpan, A., Phelan, M. M., & Wright, H. L. (2024) · Frontiers in Aging · doi:10.3389/fragi.2024.1426436 · Cited by 22
The recent development, application, and future prospects of muscle atrophy animal models
Zhang, G., Hu, F., Huang, T., Ma, X., Cheng, Y., Liu, X., Jiang, W., Dong, B., & Fu, C. (2024) · MedComm – Future Medicine · doi:10.1002/mef2.70008 · Cited by 29
Meng, L., Shi, H., Wang, D., Shi, J. C., Wu, W., Dang, Y.-M., Fan, G., Shen, J., Yu, P., Dong, J., et al. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.816045 · Cited by 23
“Of importance, the causes of impaired muscle mass and strength with aging were examined in 119 older men; the results demonstrated a fundamental role of altered mitochondrial metabolism in the pathological losses in sarcopenia among older people (67).”
BackgroundVo, T. T. T., Huynh, T. D., Wang, C., Lai, K.-H., Lin, Z., Lin, W., Chen, Y., Peng, T., Wu, H., & Lee, I. (2022) · Antioxidants · doi:10.3390/antiox11081619 · Cited by 24
“Suggestive of potential relevance in mammals, the UPRmt network is also active in various tissues [73], which is deregulated in age-related diseases such as sarcopenia (muscle wasting and weakness) [74] and Alzheimer’s disease [75,76].”
BackgroundMaruta, H., Abe, R., & Yamashita, H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094691 · Cited by 22
“The bioenergetics of skeletal muscle largely rely on the metabolic flexibility of its mitochondria [3,4].”
BackgroundFu, Y., Tao, L., Wang, X., Wang, B., Qin, W., & Song, L. (2024) · Experimental Gerontology · doi:10.1016/j.exger.2024.112428 · Cited by 21
Age-related decline of chaperone-mediated autophagy in skeletal muscle leads to progressive myopathy
Santiago‐Fernández, O., Coletto, L., Tasset, I., Kaushik, S., Concepcion, A. R., Qaisar, R., Macho-González, A., Lindenau, K. L., Díaz, A., Khawaja, R. R., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01412-9 · Cited by 30
“…the Singapore Sarcopenia Study (SSS), which includes skeletal muscle biopsies from males who were either healthy or with sarcopenia (ages 65–79) 61 , revealed two distinct transcriptional profiles in the sarcopenic group: SP1 with low LAMP2 and CMA chaperone expression, and SP2 with higher…”
Metadata
- 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
- Migliavacca, Eugenia
- Tay, Stacey K. H.
- Patel, Harnish P.
- Civiletto, Gabriele
- McFarlane, Craig
- Barton, Sheila J.
- Leow, Melvin K.
- Antoun, Elie
- Charpagne, Aline
- Seng Chong, Yap
- Descombes, Patrick
- Francis-Emmanuel, Patrice
- Garratt, Emma S.
- Giner, Maria Pilar
- Marquis, Julien
- Metairon, Sylviane
- Moco, Sofia
- Raymond, Frederic
- Sayer, Avan A.
- Slater-Jefferies, Jo
- Syddall, Holly E.
- Titcombe, Philip
- Vaz, Candida
- Westbury, Leo D.
- Cooper, Cyrus
- Godfrey, Keith M.
- Lillycrop, Karen A.
- Karnani, Neerja
- Feige, Jerome N.
- Venue
- Nature Communications
- Published
- 2019-12-20
- Volume
- 10
- Issue
- 1
- Pages
- 5808-5808
- ISSN
- 2041-1723 (ISSN-L)
- 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
- gold
- doi.org
- 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 (medical) › 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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