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={U. Brunk and A. 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… Expand
The lysosomal-mitochondrial axis theory of postmitotic aging and cell death.
TLDR
The mitochondrial-lysosomal axis theory of aging is proposed, according to which mitochondrial turnover progressively declines with age, resulting in decreased ATP production and increased oxidative damage. Expand
Mitochondrial turnover and aging of long-lived postmitotic cells: the mitochondrial-lysosomal axis theory of aging.
TLDR
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. Expand
The aging myocardium: roles of mitochondrial damage and lysosomal degradation.
TLDR
This work has shown that interrelated mitochondrial and lysosomal damage eventually results in functional failure and death of cardiac myocytes, which is an important contributor to overall mortality at old age. Expand
Mitochondrial recycling and aging of cardiac myocytes: the role of autophagocytosis
TLDR
It is tentatively concluded that large mitochondria selectively accumulate in aging post-mitotic cells because they are poorly autophagocytosed, and it is suggested that imperfect autophagic recycling of these critical organelles may underlie the progressive mitochondrial damage, which characterizes agingPost-Mitotic cells. Expand
Aging of Cardiac Myocytes in Culture: Oxidative Stress, Lipofuscin Accumulation, and Mitochondrial Turnover
TLDR
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. Expand
Autophagy, organelles and ageing
TLDR
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. Expand
The Involvement of Lysosomes in Myocardial Aging and Disease
TLDR
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. Expand
Mitochondrial damage and intralysosomal degradation in cellular aging.
TLDR
Lipofuscin-loaded lysosomes, in turn, poorly turn over mitochondria that gradually leads to the overload of long-lived postmitotic cells with "garbage" material, decreased adaptability and eventual cell death. Expand
Catabolic Insufficiency and Aging
  • A. Terman
  • Biology, Medicine
  • 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. Expand
Autophagy, ageing and apoptosis: the role of oxidative stress and lysosomal iron.
TLDR
The regulation of the lysosomal content of redox-active iron seems to be essential for the survival of cells both in the short- and the long-term. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 61 REFERENCES
A novel hypothesis of lipofuscinogenesis and cellular aging based on interactions between oxidative stress and autophagocytosis.
TLDR
A novel hypothesis of lipofuscin formation is proposed that H2O2 generated by mitochondria and other organelles permeates into the lumen of secondary lysosomes, which contain iron derived from cellular structures undergoing intralysosomal degradation. Expand
A proposed refinement of the mitochondrial free radical theory of aging
TLDR
This paper proposes a mechanism, based on a previously unexplored hypothesis for the proliferation of mutant mitochondrial DNA: that mitochondria with reduced respiratory function, due to a mutation or deletion affecting the respiratory chain, suffer less frequent lysosomal degradation, because they inflict free radical damage more slowly on their own membranes. Expand
Oxidative damage to mitochondrial DNA and its relationship to ageing.
  • C. Richter
  • Biology, Medicine
  • The international journal of biochemistry & cell biology
  • 1995
TLDR
Major unresolved questions concerning the role of mtDNA changes in ageing are addressed and future studies promise to clarify the possible causal relationship between mitochondrial dysfunction, reactive oxygen species production, mtDNA modifications, and ageing. Expand
A lysosomal protease enters the death scene.
  • G. Salvesen
  • Biology, Medicine
  • The Journal of clinical investigation
  • 2001
TLDR
To this point there has been little reason to believe that lysosomes participate in bona fide physiological apoptosis, but the last five years have seen a rapid advance in understanding of the genetics and biochemistry of cell death. Expand
Lysosomal involvement in apoptosis
TLDR
Dysfunction of apoptosis has been invoked in a variety of pathological conditions, such as developmental disorders, cancer, AIDS, atherosclerosis, aging, and autoimmune and neurodegenerative diseases. Expand
Garbage catastrophe theory of aging: imperfect removal of oxidative damage?
  • A. Terman
  • Chemistry, Medicine
  • Redox report : communications in free radical research
  • 2001
TLDR
It is believed that the process of aging may derive from imperfect clearance of oxidatively damaged, relatively indigestible material, the accumulation of which further hinders cellular catabolic and anabolic functions. Expand
Oxidative damage during aging targets mitochondrial aconitase.
TLDR
It is shown that mitochondrial aconitase, an enzyme in the citric acid cycle, is a specific target of oxidative damage during aging of the housefly and allows for the assessment of the physiological age of a specific individual and provides a method for the evaluation of treatments designed to affect the aging process. Expand
Ceroid/lipofuscin formation in cultured human fibroblasts: the role of oxidative stress and lysosomal proteolysis
TLDR
The results suggest that ceroid/lipofuscin forms within secondary lysosomes due to peroxidative damage of autophagocytosed material, and it is not substantially eliminated from non-dividing cells by degradation or exocytosis. Expand
Lipofuscin: Mechanisms of formation and increase with age
  • A. Terman, U. Brunk
  • Biology, Medicine
  • APMIS : acta pathologica, microbiologica, et immunologica Scandinavica
  • 1998
TLDR
The present knowledge of age pigment formation is outlined, possible mechanisms responsible for the increase of lipofuscin with age are considered, and oxidative reactions are considered to act as age‐independent enhancers of lip ofuscin accumulation. Expand
Mitochondrial production of pro-oxidants and cellular senescence.
TLDR
It is argued that the rate of mitochondrial O2- and H2O2 generation rather than the antioxidant level may act as a longevity determinant. Expand
...
1
2
3
4
5
...