Cited by 230Autophagy in Disease and TherapyTelomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model Organisms

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How autophagy both activates and inhibits cellular senescence

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Kang, Chanhee, Elledge, Stephen J.·2016·Autophagy

DOI 10.1080/15548627.2015.1121361PMC PMC4854549

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Abstract

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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Background
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Ling, Q., Zhang, Y., Chang, W., Liu, S.-T., Zhu, H.-L., & Wang, H. (2024) · Chemosphere · doi:10.1016/j.chemosphere.2024.142138 · Cited by 9
Delaying Renal Aging: Metformin Holds Promise as a Potential Treatment
Qiao, Z., Zhao, J., Yuan, J., Qin, Y., Zhu, Z., Liu, J., & Sun, S. (2024) · Aging and Disease · doi:10.14336/ad.2024.0168 · Cited by 10
“Kang et al. [112] provided a summary of the mechanisms by which autophagy regulates aging.”
Interaction between Autophagy and Senescence in Pancreatic Beta Cells
Hela, F., & Aguayo‐Mazzucato, C. (2023) · Biology · doi:10.3390/biology12091205 · Cited by 9
“In terms of affecting each other, the relationship between autophagy and senescence is still contradictory [98].”
Background
The Potential of Naturally Derived Compounds for Treating Chronic Kidney Disease: A Review of Autophagy and Cellular Senescence
Teh, Y. M., Mualif, S. A., Noh, N. I. M., & Lim, S. K. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms26010003 · Cited by 8
“According to Kang et al. (2016), general autophagy supports the transition to senescence, whereas selective autophagy suppresses CS by degrading the senescence regulator (GATA4) [17].”
Influential
Blocking ACSL6 Compromises Autophagy via FLI1‐Mediated Downregulation of COLs to Radiosensitize Lung Cancer
Ding, W., Bao, S., Zhao, Q. D., Hao, W., Fang, K., Xiao, Y., Lin, X., Zhao, Z., Xu, X., Cui, X., et al. (2024) · Advanced Science · doi:10.1002/advs.202403202 · Cited by 7
SuoquanYishen formula improves renal cellular senescence by inhibiting YTHDF1-Rubicon axis to promote autophagy in diabetic kidney disease
Yan, Z., Zhang, L., Ma, T., Yuan, Y., Kang, Y., Liu, S., Chen, B., Li, K., Xiao, M., & Xie, Y. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1543277 · Cited by 8
Targeting the stress support network regulated by autophagy and senescence for cancer treatment
Kim, J., Lee, Y., Roh, K., Kim, M.-S., & Kang, C. (2021) · Advances in cancer research · doi:10.1016/bs.acr.2021.01.003 · Cited by 7
Self-citation
Peperomin E Induces Apoptosis and Cytoprotective Autophagy in Human Prostate Cancer DU145 Cells In Vitro and In Vivo
Lin, M., Zhu, Q., Li, Y., & Pan, J. (2021) · Planta Medica · doi:10.1055/a-1348-1634 · Cited by 7
“P62 will continue to accumulate in the cytoplasm [28].”
Background
Aging-rewired metabolic cues promote autophagy and senescence via DRAM1
Yang, J., Sun, H., Xu, K., Zhang, X., Huang, M., Jin, G., Liu, Y., Chen, W., Lin, S., Shen, J., et al. (2025) · Autophagy · doi:10.1080/15548627.2025.2568487 · Cited by 6
“…both pro-and anti-proliferative effects of autophagy have been described in the senescent process of HsMSCs [33] and liver regeneration in aged rodent models [34,35], which likely result from different interventions or distinct components of the autophagic machinery being recruited [36,37].”
Orally ingested nanosilica causes liver-specific accumulation and induces liver senescence and fibrosis via the microbiota-gut-liver axis
Han, X., Du, L., Dou, Y., Wang, H., Lv, M., Wang, L., Xiao, J., Yin, J., & Wu, J. (2025) · Journal of Nanobiotechnology · doi:10.1186/s12951-025-03711-5 · Cited by 9
“Autophagy and cellular senescence are indispensable stress responses for maintaining homeostasis in the body [28].”
FYCO1 regulates autophagy and senescence via PAK1/p21 in cataract
Chen, S., Zhao, W., Chen, R., Sheng, F., Gu, Y., Hao, S., Wu, D., Lu, B., Chen, L., Wu, Y., et al. (2024) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2024.110180 · Cited by 8
mTOR‐autophagy promotes pulmonary senescence through IMP1 in chronic toxicity of methamphetamine
Zhu, M., Liu, B., Shi, L., Wang, X., & Wang, Y. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15841 · Cited by 6
Immune cell senescence and exhaustion promote the occurrence of liver metastasis in colorectal cancer by regulating epithelial-mesenchymal transformation
Lin, S., Ma, L., Mo, J., Zhao, R., Li, J., Yu, M., Jiang, M., & Peng, L. (2024) · Aging · doi:10.18632/aging.205778 · Cited by 5
Trimethylamine-N-oxide promotes vascular aging via inhibiting GATA4 degradation in chronic kidney disease rats
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Role of apoptosis, autophagy, and the unfolded protein response in glioblastoma chemoresistance
Dastghaib, S., Hajiahmadi, S., Seyfoori, A., Amereh, M., Zamani, M., Shahsavari, Z., Shojaei, S., Akbari, M., Mokarram, P., & Ghavami, S. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821567-8.00016-6 · Cited by 6
Identification and experimental verification of senescence-related gene signatures and molecular subtypes in idiopathic pulmonary arterial hypertension
Meng, Z., Lu, C., Li, J., Liao, J., Wen, H., Li, Y., Huang, F., & Zeng, Z. (2024) · Scientific Reports · doi:10.1038/s41598-024-72979-8 · Cited by 6
“Autophagy plays an important role in cell homeostasis, and the inhibition of autophagy leads to an increase in reactive oxygen species, which leads to cell senescence 54 .”
Effect of Ultraviolet B Irradiation on Melanin Content Accompanied by the Activation of p62/GATA4-Mediated Premature Senescence in HaCaT Cells
Yan, J., Ma, L., Liu, F., Sun, B., Tian, M., Lu, X., Liu, H.-X., Gao, L., & Liu, Q.-J. (2022) · Dose-Response · doi:10.1177/15593258221075321 · Cited by 5
“Premature senescence is characterized by several physiological changes, including the decreased capacity of proliferation, increased bulk, increased number of lysosomes, and increased expression of senescence-associated genes, and is induced by various factors, such as DNA damage and oxidative stress.(11) UVB can pene…”
Background
Identification of an independent autophagy-gene prognostic index for papillary renal cell carcinoma
Wei, X., Wang, W., Wang, H., Wang, Y., Wang, Y., Li, G., Ji, C., Ren, X., Song, N., & Qin, C. (2020) · Translational Andrology and Urology · doi:10.21037/tau-20-906 · Cited by 5
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Avelar, R. A., Duffield, T., Lagger, C., Krstevska, N., Breuer, M., & de Magalhães, J. P. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.03.616489 · Cited by 5
New insights into the role of cellular senescence and rheumatic diseases
Wen, J., Li, J., Wan, L., & Wang, F. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1557402 · Cited by 6
Integration of Transcriptomic and Single-Cell Data to Uncover Senescence- and Ferroptosis-Associated Biomarkers in Sepsis
Zhang, X., Zhou, Y., Li, H., Chen, M., Peng, F., & Li, N. (2025) · Biomedicines · doi:10.3390/biomedicines13040942 · Cited by 4
“The results revealed that these genes were significantly enriched in several critical biological pathways, including cellular senescence, regulation of autophagy [46,47], oxidative stress response [48,49], response to radiation [50,51], and lipid oxidation [52,53].”
Unraveling the functional and molecular interplay between cellular senescence and the unfolded protein response
Giroud, J., Combémorel, E., Pourtier, A., Abbadie, C., & Pluquet, O. (2025) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00091.2025 · Cited by 9
Impaired autophagy activity-induced abnormal differentiation of bone marrow stem cells is related to adolescent idiopathic scoliosis osteopenia
Zhang, H., Yang, G., Li, J., Xiao, L., Guo, C., & Wang, Y. (2022) · Chinese Medical Journal · doi:10.1097/cm9.0000000000002165 · Cited by 6
Up-Regulation of GATA4 Regulates Human Lens Epithelial Cell Function in Age-Related Cataract
Xie, X., Song, X., Liu, X., Luo, X., Nabijiang, M., Ma, M., & Li, Y. (2020) · Ophthalmic Research · doi:10.1159/000507962 · Cited by 4
A protocol for rapid construction of senescent cells
Yu, X., Quan, J., Chen, S., Yang, X., Huang, S., Yang, G., & Zhang, Y. (2022) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2022.929788 · Cited by 4
“Cellular senescence refers to irreversible growth arrest that occurs in culture or in vivo as reaction to the inordinate intracellular and extracellular stress (Kowald et al., 2020).”
Background
The roles of stress‐induced premature senescence and Akt/ FoxO1 signaling in periapical lesions
Liu, Q., Li, S., Tang, T., & Wu, Y. (2023) · Oral Diseases · doi:10.1111/odi.14703 · Cited by 3
Non-Mutational Changes of Autophagy Marker LC3A in Patients with Acute Myeloid Leukemia; Effect of DNA Methylation and Expression Level of LncRNA-GAS5 and miRNA-155-5p, A Case Control Study
Amiri, ‏., Mirzaeian, A., & Noroozi‐Aghideh, A. (2024) · Indian Journal of Hematology and Blood Transfusion · doi:10.1007/s12288-024-01765-3 · Cited by 3
“However, our data are explainable with study of Kang C and Elledge SJ which revealed that autophagy can both trigger and impede cellular senescence [39].”
Multiparametric identification of putative senescent cells in skeletal muscle via mass cytometry
Li, Y., Baig, N. F., Roncancio, D., Elbein, K., Lowe, D. A., Kyba, M., & Arriaga, E. A. (2024) · Cytometry Part A · doi:10.1002/cyto.a.24853 · Cited by 3
“Prior work reports that inhibition of autophagy delays senescence and SASP, while general autophagy increases during cellular senescence [28], despite a decline of autophagy function with aging [29].”
RORA Regulates Autophagy in Hair Follicle Stem Cells by Upregulating the Expression Level of the Sqstm1 Gene
Zhao, X., Xu, Y., Li, S., et al. (2025) · Biomolecules · doi:10.3390/biom15020299 · Cited by 2
“Autophagy can be classified based on its occurrence mode into macroautophagy, microautophagy, and chaperone-mediated autophagy; it can also be categorized based on the selectivity of degraded substrates into selective autophagy and non-selective autophagy [9–11].”
Glycophagy: molecular mechanisms, regulatory signals, and disease associations
Chen, L., Jiang, J., Meiqing, L., & Chen, L. (2026) · Autophagy Reports · doi:10.1080/27694127.2025.2595375 · Cited by 4
Cellular senescence in skeletal muscle: myogenic and nonmyogenic cell populations, mechanisms, and therapeutic opportunities
Παπανικολάου, Κ., Yadav, A., Mankowski, R. T., Alexander, M. S., Gamboa, J. L., Thalacker‐Mercer, A. E., Dungan, C. M., & Englund, D. A. (2026) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00876.2025 · Cited by 2
Integrating bulk and single-cell transcriptomics to elucidate the role and potential mechanisms of autophagy in aging tissue
Zhu, Z., Li, L., Ye, Y., & Zhong, Q. (2024) · Cellular Oncology · doi:10.1007/s13402-024-00996-w · Cited by 3
“Although recent studies suggest a genetic connection between autophagy and aging, the positive or negative impact of autophagy on aging remains controversial [14].”
PM2.5-induced cellular senescence drives brown adipose tissue impairment in middle-aged mice
Hu, R., Fan, W., Li, S., Zhang, G., Zang, L., Li, Q., Li, R., Chen, R., Zhang, L., Gu, W., et al. (2024) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2024.116423 · Cited by 1
“Cellular senescence has been demonstrated to have complex interactions with apoptosis and autophagy homeostasis (Banimohamad--Shotorbani et al., 2020; Kang and Elledge, 2016).”

Authors: Kang, C., & Elledge, S. J.
Affiliations: Brigham and Women's Hospital (US)
Corresponding author: Elledge, Stephen J.
ORCID: Kang, Chanhee
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
DOI: 10.1080/15548627.2015.1121361
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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How autophagy both activates and inhibits cellular senescence

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