The mitochondrial-lysosomal axis theory of aging: accumulation of damaged mitochondria as a result of imperfect autophagocytosis.

@article{Brunk2002TheMA,
  title={The mitochondrial-lysosomal axis theory of aging: accumulation of damaged mitochondria as a result of imperfect autophagocytosis.},
  author={Ulf T. Brunk and Alexei Terman},
  journal={European journal of biochemistry},
  year={2002},
  volume={269 8},
  pages={
          1996-2002
        }
}
Cellular manifestations of aging are most pronounced in postmitotic cells, such as neurons and cardiac myocytes. Alterations of these cells, which are responsible for essential functions of brain and heart, are particularly important contributors to the overall aging process. Mitochondria and lysosomes of postmitotic cells suffer the most remarkable age-related alterations of all cellular organelles. Many mitochondria undergo enlargement and structural disorganization, while lysosomes, which… 

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

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In this review, the importance of crosstalk between mitochondria and lysosomes in aging is stressed and the slow accumulation of lipofuscin within lysOSomes seems to depress autophagy, resulting in reduced turnover of effective mitochondria.

Aging of Cardiac Myocytes in Culture: Oxidative Stress, Lipofuscin Accumulation, and Mitochondrial Turnover

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The results suggest that both lipofuscin accumulation and mitochondrial damage have common underlying mechanisms, likely including imperfect autophagy and ensuing lysosomal degradation of oxidatively damaged mitochondria and other organelles.

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Lipofuscin deposition hampers autophagic mitochondrial turnover, promoting the accumulation of senescent mitochondria, which are deficient in ATP production but produce increased amounts of reactive oxygen species, and culminating in cell death.

The Involvement of Lysosomes in Myocardial Aging and Disease

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Lysosomal destabilization is of importance in the induction and/or execution of programmed cell death (either classical apoptotic or autophagic), which is a common manifestation of myocardial aging and a variety of cardiac pathologies.

Catabolic Insufficiency and Aging

  • A. Terman
  • Biology
    Annals of the New York Academy of Sciences
  • 2006
TLDR
With advancing age, lipofuscin‐loaded lysosomes and defective mitochondria occupy increasingly larger parts of long‐lived postmitotic cells, leaving less and less capability for normal turnover and ATP production, finally resulting in cell death.

Autophagy, ageing and apoptosis: the role of oxidative stress and lysosomal iron.

...

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