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How autophagy both activates and inhibits cellular senescence
Open accessAbstract
Autophagy and cellular senescence are stress responses essential for homeostasis. While recent studies indicate a genetic relationship between autophagy and senescence, whether autophagy acts positively or negatively on senescence is still subject to debate. Although autophagy was originally recognized as a nonspecific lysosomal degradation pathway (general autophagy), increasing evidence supports a selective form of autophagy that mediates the degradation of specific targets (selective autophagy). Our recent study revealed distinctive roles of selective autophagy and general autophagy in the regulation of senescence, at least in part resolving apparently contradictory reports regarding the relationship between these 2 important homeostatic stress responses.
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“Senescent cells are generally characterized by increased lysosomal content occurring as a consequence of defective lysosomal turnover24 or of multi-faceted changes in autophagy25.”
From Algorithmic assessment of cellular senescence in experimental and clinical specimens (2021) · cites this paper as [25]
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Items 201–230 of 230
The Role of Sirtuins in Cellular Senescence and the Development of Age-Associated Diseases
Markelov, V. A., Akhmadishina, L. Z., Кочетова, О. В., Эрдман, В. В., & Korytina, G. F. (2025) · Russian Journal of Genetics · doi:10.1134/s1022795425700152 · Cited by 1
“Auto-phagy utilizes several alternative signaling pathways that may have opposing effects on cellular senescence [76].”
Chen, F., Xu, Z., Bai, X., He, Y., Zhou, R., Bai, X., & Zhu, Y. (2026) · The FASEB Journal · doi:10.1096/fj.202502730rr · Cited by 2
Activation-Induced Cell Death of T Cells in Human Aging
Sikora, E., & Brzezińska, A. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_15 · Cited by 1
Bai, S.-R., Zhao, Q., Jia, H., He, F., & Wang, X. (2024) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2023-0432 · Cited by 1
Effects of a prolonged diet regimen on autophagic function in rat islets with aging
Gu, Z., Miao, X., Cui, J., Yang, F., Ma, L.-C., Li, C., Sun, B., & Yan, S. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2021.111659 · Cited by 2
Yao, M., Wu, Y., Cao, Y., Liu, H., Ma, N., Chai, Y., Zhang, S., Zhang, H., Nong, L., Li, L., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-201782/v1 · Cited by 1
Targeting hepatic stellate cells to prevent or reverse liver fibrosis
Zhang, M. (2020) · University of Groningen research database (University of Groningen / Centre for Information Technology) · doi:10.33612/diss.146692010
Role of autophagy in dysregulation of oral mucosal homeostasis
Yasunaga, M., Yamaguchi, M., Seno, K., Yoshida, M., & Ohno, J. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-88526-3.00006-3
An Insight of Autophagy and Cellular Senescence: One Promising Approach for Senescence Delaying
(2022) · Journal of Contemporary Medical Practice · doi:10.53469/jcmp.2022.04(03).11
A geroscience approach for osteosarcopenia: Autophagy and senescence as therapeutic targets
Cordero, N. P., Schoenlein, P. V., Fulzele, S., & Hill, W. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-820088-9.00031-7 · Cited by 1
Activation-Induced Cell Death of T Cells in Human Aging
Sikora, E., & Brzezińska, A. (2018) · Springer eBooks · doi:10.1007/978-3-319-64597-1_15-1
Yao, M., Wu, Y., Cao, Y., Liu, H., Ma, N., Chai, Y., Zhang, S., Zhang, H., Nong, L., Li, L., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-227734/v1
Ma, L.-P., Liu, F., Sun, B., et al. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4199000
Yu, Y., Ren, Y., Li, Y., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-2081442/v1
Molecular basis of senescence in osteoarthritis
Lawson, M. G., & Ritchison, H. M. (2024) · doi:10.32948/ajsep.2024.11.22 · Cited by 2
“Moreover, conflicting evidence exists regarding autophagy's overall impact on senescence, with studies suggesting both promoting and protective roles in different contexts [94].”
Microbiome: Friend or Friendly Foe
Reddy, L. B., & Saier, M. H. (2025) · Microbial Physiology · doi:10.1159/000548748 · Cited by 1
“Experimental evidence obtained using animal models has confirmed the causal relationship between a decline of autophagy, and aging through impaired autophagic flux and exacerbated cell damage, promoting age-related diseases [97].”
Periostin as a diagnostic marker and therapeutic target for intervertebral disc degeneration
Yuan, Y., Xu, M., Tian, Q., Sun, H., & Sun, J. (2025) · Journal of Orthopaedic Surgery and Research · doi:10.1186/s13018-025-06463-y
“In IDD, autophagy has a “double-edged sword” effect: in the early stage of degeneration, the activation of autophagy slows down the degradation rate of the ECM and effectively reduce cell death, thus serving as a protective factor [26].”
Zhou, L., Huo, M., Qian, X., Ding, L., Yu, L., Feng, W., Cui, X., & Chen, Y. (2021) · Figshare · doi:10.6084/m9.figshare.14457263
Zhang, X., Hu, X., Zhang, Y., Liu, B., Haihong, P., Liu, Z., Yao, Z., Zhu, Q., Wu, C., & Shen, T. (2024) · Figshare · doi:10.6084/m9.figshare.26571799
Long, D., Lin, Z., Li, Z., Li, M., Zhao, X., Deng, Z., Jiang, Z., Li, W., Zhong, Y., He, A., et al. (2026) · Molecular Biomedicine · doi:10.1186/s43556-026-00441-4 · Cited by 1
“Defective autophagy has been reported to drive senescence in various pathological conditions, including pulmonary fibrosis, cancer, aging-related disorders, and cardiovascular diseases [38].”
Transcriptional regulation in cardiovascular aging
Fan, Y., Song, C., Feng, F., Xun, Q., Lu, Y., & Li, C. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2026.1752877
“In addition, these transcriptional regulatory mechanisms closely link various aging markers, such as telomere damage, mitochondrial dysfunction, autophagy decline, metabolic disorders, and mechanical stress changes, through TFs such as FOXC1, GATA4, SOX9, and epigenetic modifications such as SIRT6, and jointly promote…”
InfluentialRabiei, F., Askari, H., Vala, A., Mardazad, M., & Ghasemi‐Kasman, M. (2026) · Current Clinical Pharmacology · doi:10.2174/0127724328444835260407154423
Orchestration of Autophagy and Senescence: Kinases Take the Center Stage
Basu, A. (2026) · Cells · doi:10.3390/cells15131176
Robinson, Z. R., Fong, S. C., Choi, D. Y., Siopack, S., Bolanos-Campos, A., Morshedian, N., Utke, E., Kanda, M., Kato, C., Conboy, M. J., et al. (2026) · Aging · doi:10.18632/aging.206399
“The senescent phenotype often propagates to more cells through the release of SASPs, a phenomenon known as paracrine senescence [49, 50].”
Cytostatic autophagy: an underappreciated form of autophagy and its ramifications in cancer
Elshazly, A. M., Elzahed, A. A., Allam, S., Klionsky, D. J., Radhakrishnan, S. K., & Gewirtz, D. A. (2026) · Autophagy · doi:10.1080/15548627.2026.2709937
Zhong, H., Jing, F., Guo, Y., Xu, X., Liu, L., Gao, T., & Xu, Z. (2026) · European Journal of Geriatrics and Gerontology · doi:10.4274/ejgg.galenos.2025.2025-8-4
Metadata
- Authors
- Kang, C., & Elledge, S. J.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Elledge, Stephen J.
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2016-04-29
- Volume
- 12
- Issue
- 5
- Pages
- 898-899
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC4854549
- OpenAlex
- W2344541663
- Cited by
- 228
- References
- 0
- Citations by year
- 2026: 10 · 2025: 25 · 2024: 37 · 2023: 22 · 2022: 33 · 2021: 33 · 2020: 25 · 2019: 21 · 2018: 13 · 2017: 9
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- cellular senescence, selective autophagy, lysosomal degradation, senescence regulation
- MeSH terms
- Animals, Autophagy, DNA Damage, Humans, Lysosomes, Phenotype, Cellular Senescence, GATA4 Transcription Factor
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