Macroautophagy is impaired in old murine brain tissue as well as in senescent human fibroblasts
Open accessAbstract
The overall decrease in proteolytic activity in aging can promote and accelerate protein accumulation and metabolic disturbances. To specifically analyze changes in macroautophagy (MA) we quantified different autophagy-related proteins (ATGs) in young, adult and old murine tissue as well as in young and senescent human fibroblasts. Thus, we revealed significantly reduced levels of ATG5-ATG12, LC3-II/LC3-I ratio, Beclin-1 and p62 in old brain tissue and senescent human fibroblasts. To investigate the role of mTOR, the protein itself and its target proteins p70S6 kinase and 4E-BP1 were quantified. Significant increased mTOR protein levels were determined in old tissue and cells. Determination of phosphorylated and basal amount of both proteins suggested higher mTOR activity in old murine tissue and senescent human fibroblasts. Besides the reduced levels of ATGs, mTOR can additionally reduce MA, promoting further acceleration of protein accumulation and metabolic disturbances during aging.
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The iron storage protein ferritin is enriched in ageing tissues.
“Iron accumulation occurs in replicative senescent fibroblasts in vitro [35] and the iron storage protein ferritin is enriched in ageing tissues [36], [37].”
From Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis (2018) · cites this paper as [36]
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- [4]Klionsky D.J. Abdelmohsen K. Abe A. Abedin M.J. Abeliovich H. Acevedo Arozena A. Zughaier S.M. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd ed.) Autophagy 12 2016 (1-222) PMC4835977 26799652
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- Authors
- Ott, C., König, J., Höhn, A., Jung, T., & Grune, T.
- Affiliations
- German Institute of Human Nutrition (DE)
- German Center for Diabetes Research (DE)
- German Centre for Cardiovascular Research (DE)
- Corresponding author
- Grune, Tilman
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 10
- Pages
- 266-273
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC5099282
- OpenAlex
- W2538243614
- Cited by
- 96
- References
- 45
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 11 · 2023: 8 · 2022: 13 · 2021: 15 · 2020: 6 · 2019: 14 · 2018: 5 · 2017: 7 · 2016: 2
- FWCI
- 8.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Forschungsgemeinschaft
- 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 › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- macroautophagy, aging, brain aging, cellular senescence, human fibroblasts, autophagy-related proteins, LC3-II/LC3-I ratio, Beclin-1, p62, mTOR, p70 S6 kinase, 4E-BP1, protein accumulation, metabolic disorders
- MeSH terms
- Autophagy-Related Proteins, Aging, Animals, Autophagy, Brain, Carrier Proteins, Fibroblasts, Humans, Male, Phosphoproteins, Phosphorylation, Down-Regulation, Cellular Senescence, Gene Expression Regulation, Developmental, Cell Cycle Proteins, Ribosomal Protein S6 Kinases, 70-kDa, Eukaryotic Initiation Factors, Adaptor Proteins, Signal Transducing, Mice, TOR Serine-Threonine Kinases
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