Cited by 490Autophagy in Disease and TherapyMitochondrial Function and PathologyGenetics, Aging, and Longevity in Model Organisms

Mitochondrial turnover and aging of long-lived postmitotic cells: the mitochondrial-lysosomal axis theory of aging

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Terman, Alexei, Kurz, Tino, Navratil, Marian, Arriaga, Edgar A., Brunk, Ulf T.·2010·Antioxidants & Redox Signaling

Abstract

It is now generally accepted that aging and eventual death of multicellular organisms is to a large extent related to macromolecular damage by mitochondrially produced reactive oxygen species, mostly affecting long-lived postmitotic cells, such as neurons and cardiac myocytes. These cells are rarely or not at all replaced during life and can be as old as the whole organism. The inherent inability of autophagy and other cellular-degradation mechanisms to remove damaged structures completely results in the progressive accumulation of garbage, including cytosolic protein aggregates, defective mitochondria, and lipofuscin, an intralysosomal indigestible material. In this review, we stress the importance of crosstalk between mitochondria and lysosomes in aging. The slow accumulation of lipofuscin within lysosomes seems to depress autophagy, resulting in reduced turnover of effective mitochondria. The latter not only are functionally deficient but also produce increased amounts of reactive oxygen species, prompting lipofuscinogenesis. Moreover, defective and enlarged mitochondria are poorly autophagocytosed and constitute a growing population of badly functioning organelles that do not fuse and exchange their contents with normal mitochondria. The progress of these changes seems to result in enhanced oxidative stress, decreased ATP production, and collapse of the cellular catabolic machinery, which eventually is incompatible with survival.

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Crossref · 10.1089/ars.2009.2598

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  • A decline in mitochondrial turnover caused by reduced mitochondrial biogenesis and/or inefficient mitochondrial degradation seems to be a particularly crucial factor in aging.

    “The process of aging involves a multitude of complex biological phenomena; a decline in mitochondrial turnover caused by reduced mitochondrial biogenesis and/or inefficient mitochondrial degradation seems to be a particularly crucial factor (Terman et al., 2010).”

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Authors
Terman, A., Kurz, T., Navratil, M., Arriaga, E. A., & Brunk, U. T.
Affiliations
  • Karolinska University Hospital (SE)
  • Linköping University (SE)
  • University of Minnesota,
  • University of Minnesota (US)
Corresponding author
Terman, Alexei
Venue
Antioxidants & Redox Signaling
Published
2010-02
Volume
12
Issue
4
Pages
503-535
ISSN
  • 1523-0864 (ISSN-L)
  • 1557-7716
OpenAlex
W2036229829
Cited by
490
References
271
Citations by year
2026: 17 · 2025: 18 · 2024: 20 · 2023: 21 · 2022: 24 · 2021: 30 · 2020: 35 · 2019: 30 · 2018: 33 · 2017: 37 · 2016: 38 · 2015: 34 · 2014: 40 · 2013: 37 · 2012: 37
FWCI
17.09
Type
journal article
Language
en
Open access
Locations
  • Antioxidants and Redox Signaling (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (NIH-R01)
  • National Institute on Aging (R01-AG-20866, R01AG020866)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • 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
Keywords
mitochondrial turnover, aging, postmitotic cells, autophagy, lipofuscin accumulation, reactive oxygen species, oxidative stress, mitochondrial dysfunction, protein aggregates, lysosomes, neurons, cardiomyocytes, mitochondrial fusion
MeSH terms
Animals, Autophagy, Humans, Lipofuscin, Lysosomes, Mitochondria, Mitosis, Cellular Senescence, Apoptosis, Reactive Oxygen Species, Oxidative Stress, Protease La, Mice, Rats

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