Age-related changes in the regulation of autophagic proteolysis in rat isolated hepatocytes
Abstract
During intervals between meals, autophagy is a major source of nutrients and may remove damaged organelles and membranes. Age-related changes in the regulation of autophagic proteolysis were studied by monitoring the rate of valine release from liver cells of 2-, 6-, 12-, 18-, and 24-month-old male Sprague-Dawley rats fed ad libitum, and incubated in vitro with added amino acids and 10(-7) M of insulin or glucagon. The maximum rate of proteolysis and its maximum inhibition by amino acids were reached at 6 months and declined thereafter. In contrast, the rate of protein degradation in the presence of high concentrations of amino acids was not affected by aging. The inhibitor effect of insulin was additive to that of amino acids and was not altered significantly by age. The conclusion is that altered regulation of autophagic proteolysis decreases susceptibility of older cells to lysosomal degradation, and it may lead to the accumulation of altered organelles and membranes.
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The lysosomal-autophagy system declines in a variety of tissues with age.
“Although there is conflicting evidence regarding the effect of aging on various proteolytic pathways (for reviews, see Attaix et al., 2005; Combaret et al., 2009), it has been reported that the lysosomal-autophagy system declines in a variety of tissues with age (Cuervo and Dice, 2000; Donati et al., 2001; Wohlgemuth et al., 2010).”
From New insights into the role of mitochondria in aging: mitochondrial dynamics and more (2010) · cites this paper as Donati et al., 2001
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- Authors
- Donati, A., Cavallini, G., Paradiso, C., Vittorini, S., Pollera, M., Gori, Z., & Bergamini, E.
- Affiliations
- University of Pisa (IT)
- Corresponding author
- Donati, A.
- Venue
- The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-07-01
- Volume
- 56
- Issue
- 7
- Pages
- B288-B293
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- OpenAlex
- W2005624025
- Cited by
- 110
- References
- 41
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 1 · 2019: 4 · 2018: 12 · 2017: 6 · 2016: 5 · 2015: 4 · 2014: 6 · 2013: 5 · 2012: 9
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministero dell'Università e della Ricerca
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- autophagy, aging, hepatocytes, lysosomal degradation, insulin, glucagon, amino acids, protein degradation, age-related decline
- MeSH terms
- Aging, Amino Acids, Analysis of Variance, Animals, Autophagy, Glucagon, Insulin, Liver, Male, Microscopy, Electron, Valine, Rats, Sprague-Dawley, Hepatocytes, Rats, In Vitro Techniques
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