Skeletal Muscle Energetics Explain the Sex Disparity in Mobility Impairment in the Study of Muscle, Mobility and Aging
Open accessPublished version of a preprint
Abstract
The age-related decline in muscle mitochondrial energetics contributes to the loss of mobility in older adults. Women experience a higher prevalence of mobility impairment compared to men, but it is unknown whether sex-specific differences in muscle energetics underlie this disparity. In the Study of Muscle, Mobility and Aging (SOMMA), muscle energetics were characterized using in vivo phosphorus-31 magnetic resonance spectroscopy and high-resolution respirometry of vastus lateralis biopsies in 773 participants (56.4% women, age 70–94 years). A Short Physical Performance Battery (SPPB) score ≤8 was used to define lower-extremity mobility impairment. Muscle mitochondrial energetics were lower in women compared to men (eg, Maximal Complex I&II OXPHOS: Women = 55.06 ± 15.95; Men = 65.80 ± 19.74; p < .001) and in individuals with mobility impairment compared to those without (eg, Maximal Complex I&II OXPHOS in women: SPPB ≥ 9 = 56.59 ± 16.22; SPPB ≤ 8 = 47.37 ± 11.85; p < .001). Muscle energetics were negatively associated with age only in men (eg, Maximal ETS capacity: R = −0.15, p = .02; age/sex interaction, p = .04), resulting in muscle energetics measures that were significantly lower in women than men in the 70–79 age group but not the 80+ age group. Similarly, the odds of mobility impairment were greater in women than men only in the 70–79 age group (70–79 age group, odds ratio [OR]age-adjusted = 1.78, 95% confidence interval [CI] = 1.03, 3.08, p = .038; 80+ age group, ORage-adjusted = 1.05, 95% CI = 0.52, 2.15, p = .89). Accounting for muscle energetics attenuated up to 75% of the greater odds of mobility impairment in women. Women had lower muscle mitochondrial energetics compared to men, which largely explain their greater odds of lower-extremity mobility impairment.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Epidemiology of sarcopenia: Prevalence, risk factors, and consequences
Yuan, S., & Larsson, S. C. (2023) · Metabolism · doi:10.1016/j.metabol.2023.155533 · Cited by 1,114 · see citing works
Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition
Haizlip, K. M., Harrison, B. C., & Leinwand, L. A. (2015) · Physiology · doi:10.1152/physiol.00024.2014 · Cited by 521 · see citing works
Ansdell, P., Thomas, K., Hicks, K. M., Hunter, S. K., Howatson, G., & Goodall, S. (2020) · Experimental Physiology · doi:10.1113/ep088548 · Cited by 403 · see citing works
Mitochondria: A central target for sex differences in pathologies
Ventura-Clapier, R., Moulin, M., Piquereau, J., Lemaire, C., Mericskay, M., Veksler, V., & Garnier, A. (2017) · Clinical Science · doi:10.1042/cs20160485 · Cited by 371 · see citing works
Coen, P. M., Jubrias, S. A., Distefano, G., Amati, F., Mackey, D. C., Glynn, N. W., Manini, T. M., Wohlgemuth, S. E., Leeuwenburgh, C., Cummings, S. R., et al. (2013) · The Journals of Gerontology: Series A · doi:10.1093/gerona/gls196 · Cited by 323 · see citing works
Self-citationGrevendonk, L., Connell, N. J., McCrum, C., Fealy, C. E., Bilet, L., Bruls, Y. M. H., Mevenkamp, J., Schrauwen-Hinderling, V. B., Jörgensen, J. A., Moonen-Kornips, E., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24956-2 · Cited by 298 · see citing works
Age, Obesity, and Sex Effects on Insulin Sensitivity and Skeletal Muscle Mitochondrial Function
Karakelides, H., Irving, B. A., Short, K. R., O'Brien, P., & Nair, K. S. (2010) · Diabetes · doi:10.2337/db09-0591 · Cited by 293 · see citing works
Lundsgaard, A.-M., & Kiens, B. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00195 · Cited by 289 · see citing works
Billot, M., Calvani, R., Urtamo, A., Sánchez-Sánchez, J. L., Ciccolari-Micaldi, C., Chang, M., Roller-Wirnsberger, R., Wirnsberger, G., Sinclair, A., Vaquero-Pinto, M. N., et al. (2020) · Clinical Interventions in Aging · doi:10.2147/cia.s253535 · Cited by 242 · see citing works
Sex differences in mitochondrial (dys)function: Implications for neuroprotection
Demarest, T. G., & McCarthy, M. M. (2015) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-014-9583-7 · Cited by 192 · see citing works
Konopka, A. R., Asante, A., Lanza, I. R., Robinson, M. M., Johnson, M. L., Dalla Man, C., Cobelli, C., Amols, M. H., Irving, B. A., & Nair, K. S. (2015) · Diabetes · doi:10.2337/db14-1701 · Cited by 112 · see citing works
Integrating and evaluating sex and gender in health research
Day, S., Mason, R., Lagosky, S., & Rochon, P. A. (2016) · Health Research Policy and Systems · doi:10.1186/s12961-016-0147-7 · Cited by 107 · see citing works
From mitochondria to sarcopenia: role of 17β-estradiol and testosterone
Tian, X., Lou, S., & Shi, R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1156583 · Cited by 54 · see citing works
Flagged first, then by citations
- Authors
- Kramer, P. A., Coen, P. M., Cawthon, P. M., Distefano, G., Cummings, S. R., Goodpaster, B. H., Hepple, R. T., Kritchevsky, S. B., Shankland, E. G., Marcinek, D. J., Toledo, F. G. S., Duchowny, K. A., Ramos, S. V., Harrison, S., Newman, A. B., & Molina, A. J. A.
- Affiliations
- Wake Forest University Health Sciences (US)
- AdventHealth Orlando (US)
- University of California, San Francisco (US)
- AdventHealth, Translational Research Institute , Orlando, Florida , USA
- University of Florida Health (US)
- University of Washington (US)
- University of Pittsburgh (US)
- University of Michigan (US)
- California Pacific Medical Center (US)
- University of California San Diego (US)
- Corresponding author
- Kramer, Philip A
- Molina, Anthony J A
- ORCID
- Venue
- The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2023-12-27
- Volume
- 79
- Issue
- 4
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC10960628
- OpenAlex
- W4390258132
- Cited by
- 8
- References
- 13
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- National Institute on Aging (R01AG059416, R01 AG054523, R01AG061805, U01 AG060897, R56 AG057864)
- American Diabetes Association (1-19- PDF-006)
- NIA Claude D. Pepper Older American Independence Centers (P30AG024827)
- Wake Forest University (P30AG021332)
- National Center for Advancing Translational Sciences (UL1TR001420)
- Topics
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- skeletal muscle energetics, mitochondrial function, sex differences, mobility impairment, older adults, aging, vastus lateralis, phosphorus-31 magnetic resonance spectroscopy, high-resolution respirometry, Short Physical Performance Battery, age-related muscle loss
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
