Cited by 387Autophagy in Disease and TherapyGenetics, Aging, and Longevity in Model OrganismsAntioxidant Activity and Oxidative Stress

Lipofuscin: Mechanisms of formation and increase with age

TERMAN, ALEXEI, BRUNK, ULF T.·1998·APMIS

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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Registry

Crossref · 10.1111/j.1699-0463.1998.tb01346.x

Cites

126 of 126 references verified0 citation errors · 0 not checkable

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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.”

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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

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