The effect of age on formation and elimination of autophagic vacuoles in mouse hepatocytes
Abstract
To gain an understanding of the mechanisms of lipofuscin (LF) accumulation in aging cells we studied both the formation and the elimination of autophagic vacuoles (AV) in hepatocytes of adult (5–6 months) and old (20–21 months) CBA male mice. For the evaluation of AV formation we determined the degree of AV accumulation 4 h after the injection of vinblastine, which blocks the fusion of AV with lysosomes. Other animals were treated with Triton X-100, which provokes the appearance of AV, and then, after 4 h, with cycloheximide to block the appearance of newly formed AV. AV elimination was then evaluated during the next 30 minutes. In our quantitative electron microscopic study of the liver tissue of these mice, we found a decrease in AV formation rate as well as a decrease in the intensity of AV elimination in hepatocytes of old versus young adult animals. The results indicate that the slowing down of AV elimination with age may play an important role in LF accumulation. Further, LF accumulation manifests itself despite decreased autophagy in aging.
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In old rodent livers, cargo sequestration by double membrane vesicles still takes place, but elimination of these vesicles by fusion with the lysosomal compartment is severely impaired.
“although cargo sequestration by the double membrane vesicles still takes place in the old tissues, the elimination of these vesicles by fusion with the lysosomal compartment was severely impaired (Fig. 3) (Terman, 1995)”
From Protein Homeostasis and Aging: the importance of exquisite quality control (2011) · cites this paper as Terman, 1995
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“In fact, poor clearance of already formed autophagosomes with age was one of the first defects iden - tified in autophagy in model systems (Terman, 1995 ).”
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Retracted
- Authors
- Terman, A.
- Affiliations
- D. F. Chebotarev State Institute of Gerontology of the National Academy of Medical Sciences of Ukraine (UA)
- Corresponding author
- Terman, A.
- Venue
- Gerontology
- Publisher
- S. Karger AG
- Published
- 2009-04-15
- Volume
- 41 Suppl 2
- Pages
- 319-326
- ISSN
- 0304-324X (ISSN-L)
- 1423-0003
- OpenAlex
- W2053394933
- Cited by
- 162
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 1 · 2022: 3 · 2021: 9 · 2020: 4 · 2019: 9 · 2018: 10 · 2017: 7 · 2016: 5 · 2015: 4 · 2014: 5 · 2013: 7 · 2012: 10
- FWCI
- 8.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gerontology (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 › Hepatology › Liver physiology and pathology
- Keywords
- autophagosomes, lipofuscin accumulation, aging, hepatocytes, autophagy, vinblastine, Triton X-100, cycloheximide, lysosome fusion, age-related decline
- MeSH terms
- Aging, Antineoplastic Agents, Phytogenic, Autophagy, Cells, Cultured, Lipofuscin, Lysosomes, Microscopy, Electron, Vacuoles, Vinblastine
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