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Sci. Aging Knowl. Environ., 2 February 2005
Vol. 2005, Issue 5, p. re1
[DOI: 10.1126/sageke.2005.5.re1]

REVIEWS

Lipofuscin and Aging: A Matter of Toxic Waste

Douglas A. Gray, and John Woulfe

Douglas A. Gray is at the Ottawa Regional Cancer Centre, Ottawa, Ontario, Canada K1H 1C4 and the Ottawa Health Research Institute, Ottawa, Ontario, Canada K1Y 4E9. John Woulfe is at the Ottawa Health Research Institute, Ottawa, Ontario, Canada K1Y 4E9 and in the Department of Pathology, Ottawa Hospital, Ottawa, Canada K1Y 4E9. E-mail: dgray{at}ohri.ca (D.A.G.)

http://sageke.sciencemag.org/cgi/content/full/2005/5/re1

Key Words: lipofuscin • biomarker • mitochondrial-lysosomal axis theory of aging • ubiquitin/proteasome system • neuronal ceroid lipofuscinoses • garbage catastrophe

Abstract: Lipofuscin is membrane-bound cellular waste that can be neither degraded nor ejected from the cell but can only be diluted through cell division and subsequent growth. The fate of postmitotic cells is to accumulate lipofuscin, which as an "aging pigment" has been considered a reliable biomarker for the age of cells such as neurons and, by extension, their hosts. In the aging human brain, deposits of lipofuscin are not uniformly distributed but are concentrated in specific regions of functional interest. The prevailing thought is that the major source of lipofuscin is incomplete lysosomal degradation of damaged mitochondria. Accumulating evidence suggests that lipofuscin is not benign but can impair the functioning of seemingly unrelated cellular systems, including the ubiquitin/proteasome pathway. A damaging feedback loop of lysosomal and proteasomal inhibition may occur as lipofuscin accumulates, leading to what has been appropriately named a "garbage catastrophe." Reversing this catastrophe presents a formidable challenge.

Citation: D. A. Gray, J. Woulfe, Lipofuscin and Aging: A Matter of Toxic Waste. Sci. Aging Knowl. Environ. 2005 (5), re1 (2005).

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