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Cited by 378Mitochondrial Function and PathologyMuscle Physiology and DisordersNutrition and Health in Aging

Mitochondrial DNA deletion mutations colocalize with segmental electron transport system abnormalities, muscle fiber atrophy, fiber splitting, and oxidative damage in sarcopenia

WANAGAT, JONATHAN, CAO, ZHENGJIN, PATHARE, PRANALI, AIKEN, JUDD M.·2001·The FASEB Journal
DOI 10.1096/fj.00-0320com
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Abstract

The in vivo cellular impact of age-associated mitochondrial DNA mutations is unknown. We hypothesized that mitochondrial DNA deletion mutations contribute to the fiber atrophy and loss that cause sarcopenia, the age-related decline of muscle mass and function. We examined 82,713 rectus femoris muscle fibers from Fischer 344 x Brown Norway F1 hybrid rats of ages 5, 18, and 38 months through 1000 microns by serial cryosectioning and histochemical staining for cytochrome c oxidase and succinate dehydrogenase. Between 5 and 38 months of age, the rectus femoris muscle in the hybrid rat demonstrated a 33% decrease in mass concomitant with a 30% decrease in total fibers at the muscle mid-belly. We observed significant increases in the number of mitochondrial abnormalities with age from 289 +/- 8 ETS abnormal fibers in the entire 5-month-old rectus femoris to 1094 +/- 126 in the 38-month-old as calculated from the volume density of these abnormalities. Segmental mitochondrial abnormalities contained mitochondrial DNA deletion mutations as revealed by laser capture microdissection and whole mitochondrial genome amplification. Muscle fibers harboring mitochondrial deletions often displayed atrophy, splitting and increased steady-state levels of oxidative nucleic damage. These data suggest a causal role for age-associated mitochondrial DNA deletion mutations in sarcopenia.

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  • The role of mitochondrial dysfunction in the etiology of sarcopenia has been extensively characterized.

    “The role of mitochondrial dysfunction in the etiology of sarcopenia has been extensively characterized (17, 18, 19, 20).”

    From Discovering pathways of sarcopenia in older adults: a role for insulin resistance on mitochondria dysfunction (2011) · cites this paper as [20]

  • There is substantial evidence of increased ROS production and oxidative stress-induced damage to mtDNA and ETC complexes in aged rodents and non-human primates, as well as in human vastus lateralis muscle.

    “there is substantial evidence showing increased ROS production and associated oxidative stress-induced damage to mitochondrial DNA (mtDNA) and ETC complexes in aged rodents and non-human primates (Figueiredo, Powers, Ferreira, Appell, and Duarte 2009;Lee, Choi, Birkenfeld, Alves, Jornayvaz, Jurczak, Zhang, Woo, Shadel, and Ladiges 2010;Lee, Wang, and Fanburg 1998;WANAGAT, CAO, PATHARE, and AIKEN 2”

    From Successful aging: Advancing the science of physical independence in older adults (2015) · cites this paper as WANAGAT et al. 2001

  • Mitochondrial mutations are implicated in sarcopenia because mtDNA deletions co-localized with mitochondrial malfunction in skeletal muscle fibers of aged rats.

    “Mitochondrial mutations are implicated in sarcopenia because mtDNA deletions co-localized with mitochondrial malfunction in skeletal muscle fibers of aged rats (Wanagat et al., 2001), and PCD-like events were elevated in the skeletal muscle of aging mice engineered to have greater mitochondrial mutation load (Kujoth et al., 2005).”

    From Programmed cell death in aging (2015) · cites this paper as Wanagat et al., 2001

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Authors
WANAGAT, J., CAO, Z., PATHARE, P., & AIKEN, J. M.
Affiliations
University of Wisconsin–Madison (US)
ORCID
Venue
The FASEB Journal
Publisher
Wiley
Published
2001-02
Volume
15
Issue
2
Pages
322-332
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
DOI
10.1096/fj.00-0320com
OpenAlex
W2063301281
Cited by
378
References
66
Citations by year
2026: 8 · 2025: 8 · 2024: 4 · 2023: 7 · 2022: 12 · 2021: 23 · 2020: 20 · 2019: 19 · 2018: 18 · 2017: 13 · 2016: 10 · 2015: 23 · 2014: 18 · 2013: 18 · 2012: 13
FWCI
5.68
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The FASEB Journal (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (R01 AG11604, P01 AG11915, T32 AG00213)
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 › Nutrition and Health in Aging
Keywords
sarcopenia, age-related muscle loss, muscle fiber atrophy, cytochrome c oxidase, succinate dehydrogenase, oxidative DNA damage, rectus femoris, aging, mitochondrial dysfunction
MeSH terms
Aging, Animals, Atrophy, Base Sequence, Electron Transport Complex IV, DNA Damage, DNA, Mitochondrial, Electron Transport, Hybridization, Genetic, Male, Mitochondria, Muscle, Muscular Diseases, Rats, Inbred BN, Rats, Inbred F344, Succinate Dehydrogenase, Sequence Deletion, Muscle, Skeletal, Muscle Fibers, Skeletal, Muscle Development, Rats

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