Autophagy and the cell biology of age-related disease
Abstract
Macroautophagy (autophagy) is a conserved lysosomal degradation process essential for cellular homeostasis and adaption to stress. Accumulating evidence indicates that autophagy declines with age and that impaired autophagy predisposes individuals to age-related diseases, whereas interventions that stimulate autophagy often promote longevity. In this Review, we examine how the autophagy pathway restricts cellular damage and degeneration, and the impact of these functions towards tissue health and organismal lifespan.
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Autophagy is inhibited in aging cells.
“Autophagy is inhibited in aging cells.”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [137]
Autophagy capacity decreases with age.
“Autophagy capacity decreases with age.”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [137]
Fusion of autophagosomes with lysosomes requires microtubule-based transport, tethering factors, and SNARE proteins.
“Fusion of autophagosomes with lysosomes requires microtubule-based transport, tethering factors, and SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein [SNAP] receptor) proteins (Leidal et al., 2018; Levine and Kroemer, 2019).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Leidal et al., 2018
In autophagy, damaged organelles and cellular material are enclosed in a double-membraned autophagosome and delivered to lysosomes for degradation.
“In autophagy, damaged organelles (e.g., mitochondria, lysosomes, peroxisomes) and cellular material (e.g., proteins, lipids, nucleic acids) are enclosed in a double-membraned autophagosome and delivered to lysosomes for degradation (Leidal et al., 2018; Levine and Kroemer, 2019).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Leidal et al., 2018
Prolonged stress downregulates autophagy, which could send the cell into a spiral of increased debris, mitochondrial injury, and eventual metabolic reprogramming.
“However, prolonged stress downregulates autophagy, which could send the cell into a spiral of increased debris, mitochondrial injury, and eventual metabolic reprogramming (Leidal et al., 2018; Levine and Kroemer, 2019).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Leidal et al., 2018
Reduced autophagic activity during aging is correlated to the onset of age-related diseases.
“Reduced autophagic activity during aging, which might contribute to the accumulation of damaged proteins and organelles, has been correlated to the onset of age-related diseases [71]”
From Senescence-related impairment of autophagy induces toxic intraneuronal amyloid-β accumulation in a mouse model of amyloid pathology (2023) · cites this paper as [71]
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CD44 connects autophagy decline and ageing in the vascular endothelium
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Suelves, N., Saleki, S., Ibrahim, T., Palomares, D., Moonen, S., Koper, M. J., Vrancx, C., Vadukul, D. M., Papadopoulos, N., Viceconte, N., et al. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01578-x · Cited by 43 · see citing works
Humanin-induced autophagy plays important roles in skeletal muscle function and lifespan extension
Kim, S.-J., Devgan, A., Miller, B., Lee, S. M., Kumagai, H., Wilson, K. A., Wassef, G., Wong, R., Mehta, H. H., Cohen, P., et al. (2022) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2021.130017 · Cited by 30 · see citing works
Exploring the anti-aging effects of fisetin in telomerase-deficient progeria mouse model
Zhao, R., Kou, H., Jiang, D., & Wang, F. (2023) · PeerJ · doi:10.7717/peerj.16463 · Cited by 18 · see citing works
“This natural phenomenon ultimately leads to the onset of age-related diseases and, eventually, death ( Leidal, Levine & Debnath, 2018 ).”
BackgroundAutophagy dark genes: Can we find them with machine learning?
Ranjbar, M., Yang, J. J., Kumar, P., Byrd, D. R., Bearer, E. L., & Oprea, T. I. (2023) · Natural Sciences · doi:10.1002/ntls.20220067 · Cited by 7 · see citing works
- Authors
- Leidal, A. M., Levine, B., & Debnath, J.
- Affiliations
- University of California, San Francisco (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Debnath, Jayanta
- Venue
- Nature Cell Biology
- Published
- 2018-11-26
- Volume
- 20
- Issue
- 12
- Pages
- 1338-1348
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2900968153
- Semantic Scholar
- 6198e0f8196fa09f42dbc6b734120e3ff6ab0dbb
- Cited by
- 424
- References
- 151
- Citations by year
- 2026: 27 · 2025: 62 · 2024: 52 · 2023: 53 · 2022: 58 · 2021: 68 · 2020: 65 · 2019: 39
- FWCI
- 6.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Cell Biology (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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- autophagy, macroautophagy, aging, age-related diseases, longevity, lysosomal degradation, cellular homeostasis, cell damage, autophagy modulators, lifespan
- MeSH terms
- Aging, Animals, Autophagy, Humans, Lysosomes, Models, Biological, Cardiomyopathies, Signal Transduction, Cellular Senescence, Neurodegenerative Diseases
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