Lipofuscin: Mechanisms of formation and increase with age
Abstract
Lipofuscin (age pigment) is a brown‐yellow, electron‐dense, autofluorescent material that accumulates progressively over time in lysosomes of postmitotic cells, such as neurons and cardiac myocytes. The exact mechanisms behind this accumulation are still unclear. This review outlines the present knowledge of age pigment formation, and considers possible mechanisms responsible for the increase of lipofuscin with age. Numerous studies indicate that the formation of lipofuscin is due to the oxidative alteration of macromolecules by oxygen‐derived free radicals generated in reactions catalyzed by redox‐active iron of low molecular weight. Two principal explanations for the increase of lipofuscin with age have been suggested. The first one is based on the notion that lipofuscin is not totally eliminated (either by degradation or exocytosis) even at young age, and, thus, accumulates in postmitotic cells as a function of time. Since oxidative reactions are obligatory for life, they would act as age‐independent enhancers of lipofuscin accumulation, as well as of many other manifestations of senescence. The second explanation is that the increase of lipofuscin is an effect of aging, caused by an age‐related enhancement of autophagocytosis, a decline in intralysosomal degradation, and/or a decrease in exocytosis.
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Cross-linked products that reach the lysosome through sporadic fusion with double membrane vesicles exert a potent inhibitory effect on lysosomal proteolysis by inducing posttranslational modifications in the enzymatic machinery and changing the intralysosomal milieu.
“cross-linked products that reach the lysosome through their sporadic fusion with the double membrane vesicles, exert a potent inhibitory effect on lysosomal proteolysis by directly inducing undesired posttranslational modifications in the enzymatic machinery and also by changing the properties of the intralysosomal milieu, normally optimal for functioning of these enzymes (Brunk and Terman, 2002;”
From Protein Homeostasis and Aging: the importance of exquisite quality control (2011) · cites this paper as Terman and Brunk 1998
Senescent lysosomes accumulate high levels of lipofuscin (LF) aggregates.
“Senescent lysosomes accumulate high levels of lipofuscin (LF) aggregates, auto-fluorescent lipopigments formed by lipids, metals and misfolded proteins26.”
From Algorithmic assessment of cellular senescence in experimental and clinical specimens (2021) · cites this paper as [26]
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ROS, mitochondria and the regulation of autophagy
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- Authors
- TERMAN, A., & BRUNK, U. T.
- Affiliations
- Linköping University (SE)
- Corresponding author
- TERMAN, ALEXEI
- Venue
- APMIS
- Publisher
- Wiley
- Published
- 1998-01
- Volume
- 106
- Issue
- 1-6
- Pages
- 265-276
- ISSN
- 0903-4641 (ISSN-L)
- 1600-0463
- OpenAlex
- W2050878478
- Cited by
- 387
- References
- 126
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 14 · 2023: 31 · 2022: 20 · 2021: 21 · 2020: 17 · 2019: 23 · 2018: 12 · 2017: 9 · 2016: 11 · 2015: 17 · 2014: 10 · 2013: 13 · 2012: 13
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Apmis (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- lipofuscin, aging, lysosomes, oxidative stress, free radicals, iron-catalyzed oxidation, postmitotic cells, neurons, cardiomyocytes, senescence, autophagy, exocytosis, autofluorescence
- MeSH terms
- Aging, Animals, Humans, Lipofuscin, Lysosomes, Models, Biological
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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