Muscle mitochondrial bioenergetic capacities are associated with multimorbidity burden in older adults: the Study of Muscle, Mobility and Aging (SOMMA)

Theresa Mau; Terri L Blackwell; Peggy M Cawthon; Anthony J A Molina; Paul M Coen; Giovanna Distefano; Philip A Kramer; Sofhia V Ramos; Daniel E Forman; Bret H Goodpaster; Frederico G S Toledo; Kate A Duchowny; Lauren M Sparks; Anne B Newman; Stephen B Kritchevsky; Steven R Cummings

doi:10.1093/gerona/glae101

Muscle mitochondrial bioenergetic capacities are associated with multimorbidity burden in older adults: the Study of Muscle, Mobility and Aging (SOMMA)

J Gerontol A Biol Sci Med Sci. 2024 Apr 12:glae101. doi: 10.1093/gerona/glae101. Online ahead of print.

Authors

Theresa Mau^{1

2}, Terri L Blackwell¹, Peggy M Cawthon^{1

2}, Anthony J A Molina³, Paul M Coen⁴, Giovanna Distefano⁴, Philip A Kramer⁵, Sofhia V Ramos⁴, Daniel E Forman⁶, Bret H Goodpaster⁴, Frederico G S Toledo⁷, Kate A Duchowny⁸, Lauren M Sparks⁴, Anne B Newman⁹, Stephen B Kritchevsky⁵, Steven R Cummings^{1

2}

Affiliations

¹ San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, California.
² Department of Epidemiology and Biostatistics, University of California, San Francisco, California.
³ Department of Medicine-Division of Geriatrics, Gerontology, and Palliative Care, University of California San Diego School of Medicine, La Jolla, California.
⁴ Translational Research Institute, AdventHealth, Orlando, Florida.
⁵ Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
⁶ Department of Medicine-Division of Geriatrics and Cardiology, University of Pittsburgh, Geriatrics Research, Education, and Clinical Care (GRECC), VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.
⁷ Department of Medicine-Division of Endocrinology and Metabolism, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
⁸ Social Environment and Health, Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan.
⁹ Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania.

PMID: 38605684
DOI: 10.1093/gerona/glae101

Abstract

Background: The geroscience hypothesis posits that aging biological processes contribute to many age-related deficits, including the accumulation of multiple chronic diseases. Though only one facet of mitochondrial function, declines in muscle mitochondrial bioenergetic capacities may contribute to this increased susceptibility to multimorbidity.

Methods: The Study of Muscle, Mobility and Aging (SOMMA) assessed ex vivo muscle mitochondrial energetics in 764 older adults (mean age =76.4, 56.5% women, 85.9% non-Hispanic white) by high-resolution respirometry of permeabilized muscle fibers. We estimated the proportional odds ratio (POR [95%CI]) for the likelihood of greater multimorbidity (four levels: 0 conditions, N=332; 1 condition, N=299; 2 conditions, N=98; or 3+ conditions, N=35) from an index of 11 conditions, per SD decrement in muscle mitochondrial energetic parameters. Distribution of conditions allowed for testing the associations of maximal muscle energetics with some individual conditions.

Results: Lower oxidative phosphorylation supported by fatty acids and/or complex-I and -II linked carbohydrates (e.g., Max OXPHOSCI+CII) was associated with a greater multimorbidity index score (POR=1.32[1.13,1.54]) and separately with diabetes mellitus (OR=1.62[1.26,2.09]), depressive symptoms (OR=1.45[1.04,2.00]) and possibly chronic kidney disease (OR=1.57[0.98,2.52]) but not significantly with other conditions (e.g., cardiac arrhythmia, chronic obstructive pulmonary disease).

Conclusions: Lower muscle mitochondrial bioenergetic capacities was associated with a worse composite multimorbidity index score. Our results suggest that decrements in muscle mitochondrial energetics may contribute to a greater global burden of disease and is more strongly related to some conditions than others.

Keywords: aging muscle; energetics; geroscience; mitochondria; multimorbidity.

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