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


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} (D.A.G.)

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).

Read the Full Text

Lipid metabolic perturbation is an early-onset phenotype in adult spinster mutants: a Drosophila model for lysosomal storage disorders.
S. Hebbar, A. Khandelwal, R. Jayashree, S. J. Hindle, Y. N. Chiang, J. Y. Yew, S. T. Sweeney, and D. Schwudke (2017)
Mol. Biol. Cell 28, 3728-3740
   Abstract »    Full Text »    PDF »
Exogenous Hsp70 delays senescence and improves cognitive function in aging mice.
N. V. Bobkova, M. Evgenev, D. G. Garbuz, A. M. Kulikov, A. Morozov, A. Samokhin, D. Velmeshev, N. Medvinskaya, I. Nesterova, A. Pollock, et al. (2015)
PNAS 112, 16006-16011
   Abstract »    Full Text »    PDF »
Activation of TRPML1 Clears Intraneuronal A{beta} in Preclinical Models of HIV Infection.
M. Bae, N. Patel, H. Xu, M. Lee, K. Tominaga-Yamanaka, A. Nath, J. Geiger, M. Gorospe, M. P. Mattson, and N. J. Haughey (2014)
J. Neurosci. 34, 11485-11503
   Abstract »    Full Text »    PDF »
Ataxin-1 Poly(Q)-induced Proteotoxic Stress and Apoptosis Are Attenuated in Neural Cells by Docosahexaenoic Acid-derived Neuroprotectin D1.
J. M. Calandria, P. K. Mukherjee, J. C. de Rivero Vaccari, M. Zhu, N. A. Petasis, and N. G. Bazan (2012)
J. Biol. Chem. 287, 23726-23739
   Abstract »    Full Text »    PDF »
Suppression of Phosphoinositide 3-Kinase Prevents Cardiac Aging in Mice.
Y. Inuzuka, J. Okuda, T. Kawashima, T. Kato, S. Niizuma, Y. Tamaki, Y. Iwanaga, Y. Yoshida, R. Kosugi, K. Watanabe-Maeda, et al. (2009)
120, 1695-1703
   Abstract »    Full Text »    PDF »

Science of Aging Knowledge Environment. ISSN 1539-6150