Genetic and functional changes in mitochondria associated with aging
Abstract
This review is devoted to the molecular genetics and bioenergetics of human mitochondria related to the mechanism of aging. Morphological and functional changes of mitochondria associated with age and age-related disease are overviewed with special reference to the changes in enzymes encoded by mitochondrial-inherent genome. The somatically acquired mutations and oxidative damage of the genome, which lead an individual to the fragmentation of mitochondrial DNA, cellular energy crisis, naturally occurring cell death (apoptosis), and tissue degeneration and atrophy, are reviewed with relation to the inherited point mutational genotypes and the deletion types of mitochondrial DNA. Theories of aging are discussed with disclosed evidence relevant to them. Some trials to prevent age-related damage in mitochondria are introduced for the development of what may be called mitochondrial medicine.
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MtDNA oxidation renders mtDNA more susceptible to mutation because oxidized bases are misread during replication and lead to nucleotide substitutions.
“MtDNA oxidation, in turn, renders mtDNA more susceptible to mutation because oxidized bases are misread during replication and this leads to nucleotide substitutions [118–120].”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [119]
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“These structural changes underlie functional deficiencies such as disturbed energy metabolism, and subsequent decrease in ATP production, often associated with age-dependent mitochondrial DNA mutations [48].”
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“[115] T.”
Mitochondria, oxidative stress, and antioxidant defences.
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Alzheimer β protein mediated oxidative damage of mitochondrial DNA: Prevention by melatonin
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Ageing and mammalian mitochondrial genetics
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“In aging, the most common mtDNA lesion seen is a 4977 base pair (bp) deletion (Ozawa, 1997 ).”
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“ROS have been thought to be involved in the increase in the proportion of both point mutant and deletion mutant mtDNA (Ozawa, 1997).”
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“Since then, many reports have shown age-related links between accumulation of deletions and mutations in mtDNA, accompanied by an inevitable decline in neuromuscular ef®ciency (Ozawa, 1997; Wallace, 1997; Cortopassi and Wong, 1999).”
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“Damaged mitochondria can trigger apoptotic cascades (Skulachev, 1992; Ozawa, 1997; Ozawa et al, 1997) and thus abnormal sperm mitochondria may have the potential to affect zygote fitness.”
Background
- Authors
- Ozawa, T.
- Affiliations
- Nagoya University (JP)
- Corresponding author
- Ozawa, T.
- ORCID
- Ozawa, T.
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 1997-04-01
- Volume
- 77
- Issue
- 2
- Pages
- 425-464
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W1950372811
- Cited by
- 312
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2022: 4 · 2021: 3 · 2020: 4 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 11 · 2014: 4 · 2013: 14 · 2012: 8
- FWCI
- 7.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Physiological Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- mitochondrial aging, mitochondrial DNA mutations, mitochondrial DNA deletions, mitochondrial bioenergetics, mitochondrial morphology, oxidative damage, apoptosis, age-related diseases, theories of aging, mitochondrial medicine
- MeSH terms
- Aging, Animals, DNA, Mitochondrial, Humans, Mitochondria, Models, Biological, Mutation
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