Mitochondria and Aging

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

Terman A, Kurz T, Navratil M, Arriaga EA, Brunk UT.
Source

Department of Clinical Pathology and Cytology, Karolinska University Hospital, Huddinge, Stockholm, Sweden. alexei.terman@ki.se
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.

image_pdfimage_print
Liked it? Take a second to support me on Patreon.

Leave a Comment:

2 comments
Bruce Bowen says June 19, 2015

Dennis, have you seen this?

The effects of piracetam on lipofuscin of the rat cerebellar and hippocampal neurons after long-term alcohol treatment and withdrawal: a quantitative study.

http://www.ncbi.nlm.nih.gov/pubmed/1755517

Reply
    P. D. Mangan says June 19, 2015

    Bruce, thanks, very interesting. Looks like piracetam could have some fairly profound anti-aging effects.

    Reply
Add Your Reply