Lower muscle mitochondrial energetics is associated with greater phenotypic frailty in older women and men: the Study of Muscle, Mobility and Aging

• Published in: GeroScience 2024-04, Vol.46 (2), p.2409-2424
• Main Authors: Mau, Theresa, Barnes, Haley N., Blackwell, Terri L., Kramer, Philip A., Bauer, Scott R., Marcinek, David J., Ramos, Sofhia V., Forman, Daniel E., Toledo, Frederico G. S., Hepple, Russell T., Kritchevsky, Stephen B., Cummings, Steven R., Newman, Anne B., Coen, Paul M., Cawthon, Peggy M.
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate; Aged; Aging; Biomedical and Life Sciences; Carbohydrates; Cell Biology; Female; Frail Elderly; Frailty; Geriatrics/Gerontology; Humans; Life Sciences; Magnetic resonance spectroscopy; Male; Mitochondria; Mobility; Molecular Medicine; Muscles; Older people; Original; Original Article; Oxygen consumption; Physical activity; Population studies
• ISSN: 2509-2723; 2509-2715; 2509-2723
• DOI: 10.1007/s11357-023-01002-1

Background Phenotypic frailty syndrome identifies older adults at greater risk for adverse health outcomes. Despite the critical role of mitochondria in maintaining cellular function, including energy production, the associations between muscle mitochondrial energetics and frailty have not been widely explored in a large, well-phenotyped, older population. Methods The Study of Muscle, Mobility and Aging (SOMMA) assessed muscle energetics in older adults (N = 879, mean age = 76.3 years, 59.2% women). 31 Phosporous magnetic resonance spectroscopy measured maximal production of adenosine triphosphate (ATP max ) in vivo , while ex vivo high-resolution respirometry of permeabilized muscle fibers from the vastus lateralis measured maximal oxygen consumption supported by fatty acids and complex I- and II-linked carbohydrates (e.g., Max OXPHOS CI+CII ). Five frailty criteria, shrinking, weakness, exhaustion, slowness, and low activity, were used to classify participants as robust (0, N = 397), intermediate (1-2, N = 410), or frail (≥ 3, N = 66). We estimated the proportional odds ratio (POR) for greater frailty, adjusted for multiple potential confounders. Results One-SD decrements of most respirometry measures (e.g., Max OXPHOS CI+CII , adjusted POR = 1.5, 95%CI [1.2,1.8], p = 0.0001) were significantly associated with greater frailty classification. The associations of ATP max with frailty were weaker than those between Max OXPHOS CI+CII and frailty. Muscle energetics was most strongly associated with slowness and low physical activity components. Conclusions Our data suggest that deficits in muscle mitochondrial energetics may be a biological driver of frailty in older adults. On the other hand, we did observe differential relationships between measures of muscle mitochondrial energetics and the individual components of frailty.