Reduced amount of mitochondrial DNA in aged human muscle
Abstract
Muscle concentrations of mRNAs encoded by mitochondrial DNA (mtDNA) decline with aging. To determine whether this can be explained by diminished mtDNA levels, we measured the relative concentrations of mtDNA and a representative mtDNA transcript [encoding cytochrome-c oxidase, subunit 2 (COX-2)] in muscle of young (21-27 yr) and older subjects (65-75 yr). The amount of COX-2 mRNA (relative to 28S rRNA) was 22% lower (P = 0.04) in older muscle, and the amount of mtDNA (relative to nuclear DNA) was 38% lower (P = 0.0002). The average level of mitochondrial transcription factor A (Tfam), a protein essential for mtDNA replication, was similar in younger and older muscle. Tfam mRNA, nuclear respiratory factor-1 mRNA, and several mRNAs encoding proteins required for mtDNA replication were expressed at similar levels in younger and older muscle. The mtDNA concentrations were only weakly related to age-adjusted aerobic fitness (maximal oxygen consumption) and self-reported physical activity levels. We conclude that the lower concentration of mitochondrial mRNAs in older muscle can be explained by a reduced concentration of mtDNA.
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Multiple groups have reported a decrease in skeletal muscle mitochondrial content and function with age.
“Multiple groups have reported a decrease in skeletal muscle mitochondrial content and function with age.126-128”
From Hormonal and Metabolic Changes of Aging and the Influence of Lifestyle Modifications (2021) · cites this paper as [128]
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- Authors
- Welle, S., Bhatt, K., Shah, B., Needler, N., Delehanty, J. M., & Thornton, C. A.
- Affiliations
- Departments of Medicine,
- University of Rochester Medicine (US)
- ORCID
- Thornton, Charles A.
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 2003-04-01
- Volume
- 94
- Issue
- 4
- Pages
- 1479-1484
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W2147965185
- Cited by
- 86
- References
- 29
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 5 · 2014: 4 · 2013: 4 · 2012: 4
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG18254, AG17891, P30AG018254, R01AG017891)
- National Center for Research Resources (RR-00044, M01RR000044)
- Topics
- 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
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- mitochondrial DNA, muscle aging, COX-2 mRNA, TFAM, NRF1, mitochondrial DNA replication, cardiorespiratory fitness, physical activity, skeletal muscle
- MeSH terms
- Adult, Aged, Aging, DNA, Mitochondrial, Female, Humans, Isoenzymes, Male, Membrane Proteins, Osmolar Concentration, Oxygen Consumption, Physical Fitness, Prostaglandin-Endoperoxide Synthases, RNA, Messenger, Exercise, Muscle, Skeletal, Cyclooxygenase 2
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