Upregulation of the Autophagy Adaptor p62/SQSTM1 Prolongs Health and Lifespan in Middle-Aged Drosophila
Open accessAbstract
Autophagy, a lysosomal degradation pathway, plays crucial roles in health and disease. p62/SQSTM1 (hereafter p62) is an autophagy adaptor protein that can shuttle ubiquitinated cargo for autophagic degradation. Here, we show that upregulating the Drosophila p62 homolog ref(2)P/dp62, starting in midlife, delays the onset of pathology and prolongs healthy lifespan. Midlife induction of dp62 improves proteostasis, in aged flies, in an autophagy-dependent manner. Previous studies have reported that p62 plays a role in mediating the clearance of dysfunctional mitochondria via mitophagy. However, the causal relationships between p62 expression, mitochondrial homeostasis, and aging remain largely unexplored. We show that upregulating dp62, in midlife, promotes mitochondrial fission, facilitates mitophagy, and improves mitochondrial function in aged flies. Finally, we show that mitochondrial fission is required for the anti-aging effects of midlife dp62 induction. Our findings indicate that p62 represents a potential therapeutic target to counteract aging and prolong health in aged mammals.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Boosting mitophagy by overexpressing PINK1, Parkin, DRP1, or p62 in Drosophila muscles improves age-dependent muscle function deterioration and extends lifespan.
“Boosting mitophagy by overexpressing PINK1, Parkin, DRP1, or p62 in Drosophila muscles improves the age-dependent muscle function deterioration and extends lifespan [214, 236, 237].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [237]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351 · see citing works
Autophagy in the Pathogenesis of Disease
Levine, B., & Kroemer, G. (2008) · Cell · doi:10.1016/j.cell.2007.12.018 · Cited by 7,069 · see citing works
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894 · see citing works
Cui, C., Cui, J., Jin, F., Cui, Y., Li, R., Jiang, X., Tian, Y., Wang, R. C., Jiang, P., & Gao, J. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479571 · Cited by 5,214 · see citing works
Pankiv, S., Clausen, T. H., Lamark, T., Brech, A., Bruun, J.-A., Outzen, H., Øvervatn, A., Bjørkøy, G., & Johansen, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702824200 · Cited by 4,578 · see citing works
Autophagy and Viruses: Adversaries or Allies?
Dong, X., & Levine, B. (2013) · Journal of Innate Immunity · doi:10.1159/000346388 · Cited by 4,441 · see citing works
Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
Narendra, D., Tanaka, A., Suen, D.-F., & Youle, R. J. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200809125 · Cited by 4,026 · see citing works
Fission and selective fusion govern mitochondrial segregation and elimination by autophagy
Twig, G., Elorza, A., Molina, A. J. A., Mohamed, H., Wikstrom, J. D., Walzer, G., Stiles, L., Haigh, S. E., Katz, S., Las, G., et al. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601963 · Cited by 3,082 · see citing works
PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
Geisler, S., Holmström, K. M., Skujat, D., Fiesel, F. C., Rothfuss, O. C., Kahle, P. J., & Springer, W. (2010) · Nature Cell Biology · doi:10.1038/ncb2012 · Cited by 2,835 · see citing works
Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice.
Komatsu, M., Waguri, S., Koike, M., Sou, Y.-S., Ueno, T., Hara, T., Mizushima, N., Iwata, J.-I., Ezaki, J., Murata, S., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.035 · Cited by 2,124 · see citing works
The machinery of macroautophagy
Feng, Y., He, D., Yao, Z., & Klionsky, D. J. (2014) · Cell Research · doi:10.1038/cr.2013.168 · Cited by 2,083 · see citing works
The pathways of mitophagy for quality control and clearance of mitochondria
Ashrafi, G., & Schwarz, T. L. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2012.81 · Cited by 1,900 · see citing works
Selective autophagy mediated by autophagic adapter proteins
Johansen, T., & Lamark, T. (2011) · Autophagy · doi:10.4161/auto.7.3.14487 · Cited by 1,730 · see citing works
The mitochondrial basis of aging
Sun, N., Youle, R. J., & Finkel, T. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.01.028 · Cited by 1,441 · see citing works
Cargo recognition and trafficking in selective autophagy
Stolz, A., Ernst, A., & Dikic, I. (2014) · Nature Cell Biology · doi:10.1038/ncb2979 · Cited by 1,207 · see citing works
Rambold, A. S., Kostelecky, B., Elia, N., & Lippincott‐Schwartz, J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1107402108 · Cited by 1,144 · see citing works
Kaushik, S., & Cuervo, A. M. (2015) · Nature Medicine · doi:10.1038/nm.4001 · Cited by 899 · see citing works
p62/ SQSTM 1 functions as a signaling hub and an autophagy adaptor
Katsuragi, Y., Ichimura, Y., & Komatsu, M. (2015) · FEBS Journal · doi:10.1111/febs.13540 · Cited by 795 · see citing works
The Machines that Divide and Fuse Mitochondria
Hoppins, S., Lackner, L., & Nunnari, J. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.071905.090048 · Cited by 790 · see citing works
Narendra, D. P., Kane, L. A., Hauser, D. N., Fearnley, I. M., & Youle, R. J. (2010) · Autophagy · doi:10.4161/auto.6.8.13426 · Cited by 789 · see citing works
The Interplay Between Mitochondrial Dynamics and Mitophagy
Twig, G., & Shirihai, O. S. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3779 · Cited by 778 · see citing works
A conditional tissue-specific transgene expression system using inducible GAL4
Osterwalder, T., Yoon, K. S., White, B. H., & Keshishian, H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.221303298 · Cited by 770 · see citing works
Autophagy as a promoter of longevity: insights from model organisms
Hansen, M., Rubinsztein, D. C., & Walker, D. W. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0033-y · Cited by 754 · see citing works
Self-citationAutosis and autophagic cell death: the dark side of autophagy
Liu, Y., & Levine, B. (2014) · Cell Death and Differentiation · doi:10.1038/cdd.2014.143 · Cited by 746 · see citing works
Overexpression of Atg5 in mice activates autophagy and extends lifespan
Pyo, J.-O., Yoo, S.-M., Ahn, H.-H., Nah, J., Hong, S.-H., Kam, T.-I., Jung, S., & Jung, Y.-K. (2013) · Nature Communications · doi:10.1038/ncomms3300 · Cited by 721 · see citing works
Simonsen, A., Cumming, R. C., Brech, A., Isakson, P., Schubert, D. R., & Finley, K. D. (2008) · Autophagy · doi:10.4161/auto.5269 · Cited by 716 · see citing works
Prandiology of Drosophila and the CAFE assay
Ja, W. W., Carvalho, G. B., Mak, E. M., de la Rosa, N. N., Fang, A. Y., Liong, J. C., Brummel, T., & Benzer, S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702726104 · Cited by 702 · see citing works
Disruption of the beclin 1–BCL2 autophagy regulatory complex promotes longevity in mice
Fernández, Á. F., Sebti, S., Wei, Y., Zou, Z., Shi, M., McMillan, K. L., He, C., Ting, T., Liu, Y., Chiang, W.-C., et al. (2018) · Nature · doi:10.1038/s41586-018-0162-7 · Cited by 630 · see citing works
Yun, J., & Finkel, T. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.01.011 · Cited by 626 · see citing works
Rera, M., Clark, R. I., & Walker, D. W. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215849110 · Cited by 619 · see citing works
Self-citationDing, W.-X., Ni, H., Li, M., Liao, Y., Chen, X., Stolz, D. B., Dorn, G. W., & Yin, X. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.119537 · Cited by 586 · see citing works
mito-QC illuminates mitophagy and mitochondrial architecture in vivo
McWilliams, T. G., Prescott, A. R., Allen, G. F. G., Tamjar, J., Munson, M. J., Thomson, C., Muqit, M. M. K., & Ganley, I. G. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201603039 · Cited by 541 · see citing works
The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans
Lapierre, L. R., Filho, C. D. D. M., McQuary, P. R., Chu, C., Visvikis, O., Chang, J. T., Gelino, S., Ong, B., Davis, A. E. M., Irazoqui, J. E., et al. (2013) · Nature Communications · doi:10.1038/ncomms3267 · Cited by 533 · see citing works
Lee, J., Nagano, Y., Taylor, J. P., Lim, K. L., & Yao, T. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.201001039 · Cited by 517 · see citing works
Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog
Rera, M., Bahadorani, S., Cho, J., Koehler, C. L., Ulgherait, M., Hur, J. H., Ansari, W. S., Lo, T., Jones, D. L., & Walker, D. W. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.09.013 · Cited by 472 · see citing works
Self-citationAn Atg1/Atg13 Complex with Multiple Roles in TOR-mediated Autophagy Regulation
Chang, Y.-Y., & Neufeld, T. P. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-12-1250 · Cited by 418 · see citing works
Nezis, I. P., Simonsen, A., Sagona, A. P., Finley, K., Gaumer, S., Contamine, D., Rusten, T. E., Stenmark, H., & Brech, A. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200711108 · Cited by 370 · see citing works
Basal mitophagy is widespread in Drosophila but minimally affected by loss of Pink1 or parkin
Lee, J. J., Sánchez-Martínez, Á., Martinez, A., Benincá, C., Mayor, U., Clague, M. J., & Whitworth, A. J. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201801044 · Cited by 343 · see citing works
Rana, A., Rera, M., & Walker, D. W. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1216197110 · Cited by 335 · see citing works
Self-citationAMPK Modulates Tissue and Organismal Aging in a Non-Cell-Autonomous Manner
Ulgherait, M., Rana, A., Rera, M., Graniel, J. V., & Walker, D. W. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.006 · Cited by 307 · see citing works
Self-citationRana, A., Oliveira, M. P., Khamoui, A. V., Aparicio, R., Rera, M., Rossiter, H. B., & Walker, D. W. (2017) · Nature Communications · doi:10.1038/s41467-017-00525-4 · Cited by 294 · see citing works
Self-citationGenetic inactivation of p62 leads to accumulation of hyperphosphorylated tau and neurodegeneration
Ramesh Babu, J., Lamar Seibenhener, M., Peng, J., Strom, A., Kemppainen, R., Cox, N., Zhu, H., Wooten, M. C., Diaz‐Meco, M. T., Moscat, J., et al. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05340.x · Cited by 258 · see citing works
Mao, K., Wang, K., Liu, X., & Klionsky, D. J. (2013) · Developmental Cell · doi:10.1016/j.devcel.2013.05.024 · Cited by 247 · see citing works
Spatiotemporal regulation of autophagy during Caenorhabditis elegans aging
Chang, J. T., Kumsta, C., Hellman, A. B., Adams, L. M., & Hansen, M. (2017) · eLife · doi:10.7554/elife.18459 · Cited by 241 · see citing works
The PINK1–Parkin pathway is involved in the regulation of mitochondrial remodeling process
Park, J., Lee, G., & Chung, J. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.11.086 · Cited by 181 · see citing works
The RNA-Binding Protein PUM2 Impairs Mitochondrial Dynamics and Mitophagy During Aging
D’Amico, D., Mottis, A., Potenza, F., Sorrentino, V., Li, H., Romani, M., Lemos, V., Schoonjans, K., Zamboni, N., Knott, G., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2018.11.034 · Cited by 159 · see citing works
Assurance of mitochondrial integrity and mammalian longevity by the p62–Keap1–Nrf2–Nqo1 cascade
Kwon, J., Han, E., Bui, C., Shin, W., Lee, J. H., Lee, S., Choi, Y., Lee, A., Lee, K., Park, C., et al. (2012) · EMBO Reports · doi:10.1038/embor.2011.246 · Cited by 139 · see citing works
Drp1-Zip1 Interaction Regulates Mitochondrial Quality Surveillance System
Cho, H. M., Ryu, J. R., Jo, Y., Seo, T. W., Choi, Y. N., Kim, J. H., Chung, J. M., Cho, B., Kang, H. C., Yu, S.-W., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.11.009 · Cited by 117 · see citing works
Two phases of aging separated by the Smurf transition as a public path to death
Dambroise, E., Monnier, L., Ruisheng, L., Aguilaniu, H., Joly, J., Tricoire, H., & Rera, M. (2016) · Scientific Reports · doi:10.1038/srep23523 · Cited by 105 · see citing works
Age-associated oxidative damage to the p62 promoter: implications for Alzheimer disease
Du, Y., Wooten, M. C., Gearing, M., & Wooten, M. W. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.11.003 · Cited by 104 · see citing works
Wilhelm, T., Byrne, J., Amezcua, R. M., Kolundzic, E., Geisinger, J., Hajdušková, M., Tursun, B., & Richly, H. (2017) · bioRxiv · doi:10.1101/gad.301648.117 · Cited by 82 · see citing works
Relationship between growth arrest and autophagy in midgut programmed cell death in Drosophila
Denton, D., Chang, T.-K., Nicolson, S., Shravage, B., Simin, R., Baehrecke, E. H., & Kumar, S. (2012) · Cell Death & Differentiation · doi:10.1038/cdd.2012.43 · Cited by 81 · see citing works
Ávila‐Flores, A., Silverman, N. S., Díaz-Meco, M. T., & Moscat, J. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.24.8787-8795.2002 · Cited by 75 · see citing works
de Castro, I. P., Costa, A. C. O., Celardo, I., Tufi, R., Dinsdale, D. D., Loh, S. H. Y., & Martins, L. M. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.394 · Cited by 53 · see citing works
The age and evolution of an antiviral resistance mutation inDrosophila melanogaster
Bangham, J., Obbard, D. J., Kim, K.-W., Haddrill, P. R., & Jiggins, F. M. (2007) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2007.0611 · Cited by 47 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Autophagy in healthy aging and disease
Aman, Y., Schmauck-Medina, T., Hansen, M., Morimoto, R. I., Simon, A. K., Bjedov, I., Palikaras, K., Simonsen, A., Johansen, T., Tavernarakis, N., et al. (2021) · Nature Aging · doi:10.1038/s43587-021-00098-4 · Cited by 1,313 · see citing works
The Keap1-Nrf2 System: A Mediator between Oxidative Stress and Aging
Yu, C., & Xiao, J.-H. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6635460 · Cited by 537 · see citing works
Liu, Y. J., McIntyre, R. L., Janssens, G. E., & Houtkooper, R. H. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111212 · Cited by 334 · see citing works
Selective Autophagy Receptor p62/SQSTM1, a Pivotal Player in Stress and Aging
Kumar, A. V., Mills, J., & Lapierre, L. R. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.793328 · Cited by 332 · see citing works
Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging
Leduc-Gaudet, J.-P., Hussain, S. N. A., Barreiro, E., & Gouspillou, G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158179 · Cited by 268 · see citing works
“Furthermore, inactivation of autophagy regulating genes has also been associated with decreased lifespan in Caenorhabditis elegans [113], whereas promotion of autophagy in Drosophila extended lifespan [69,114].”
BackgroundWu, M., Luo, Q., Nie, R., Yang, X., Tang, Z., & Chen, H. (2020) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2020.1773390 · Cited by 207 · see citing works
Romanello, V., & Sandri, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03662-0 · Cited by 197 · see citing works
Melatonin and Autophagy in Aging-Related Neurodegenerative Diseases
Luo, F., Sandhu, A. F., Rungratanawanich, W., Williams, G. E., Akbar, M. D., Zhou, S., Song, B., & Wang, X. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197174 · Cited by 158 · see citing works
MitophAging: Mitophagy in Aging and Disease
Bakula, D., & Scheibye‐Knudsen, M. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00239 · Cited by 150 · see citing works
Kumsta, C., Chang, J. T., Lee, R., Tan, E. P., Yang, Y., Loureiro, R., Choy, E. H. Y., Lim, S. H. Y., Sáez, I., Springhorn, A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13540-4 · Cited by 139 · see citing works
The Multifaceted Role of Nutrient Sensing and mTORC1 Signaling in Physiology and Aging
Fernandes, S., & Demetriades, C. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.707372 · Cited by 124 · see citing works
Orchestration of selective autophagy by cargo receptors
Adriaenssens, E., Ferrari, L., & Martens, S. (2022) · Current Biology · doi:10.1016/j.cub.2022.11.002 · Cited by 116 · see citing works
Drp1-Zip1 Interaction Regulates Mitochondrial Quality Surveillance System
Cho, H. M., Ryu, J. R., Jo, Y., Seo, T. W., Choi, Y. N., Kim, J. H., Chung, J. M., Cho, B., Kang, H. C., Yu, S.-W., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.11.009 · Cited by 117 · see citing works
The Interplay between Mitochondrial Morphology and Myomitokines in Aging Sarcopenia
Romanello, V. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010091 · Cited by 101 · see citing works
Intestinal barrier dysfunction: an evolutionarily conserved hallmark of aging
Salazar, A. M., Aparício, R., Clark, R. I., Rera, M., & Walker, D. W. (2023) · Disease Models & Mechanisms · doi:10.1242/dmm.049969 · Cited by 96 · see citing works
Self-citationThe dialogue between the ubiquitin-proteasome system and autophagy: Implications in ageing
Sun‐Wang, J. L., Ivanova, S., & Antonio Zorzano, A. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101203 · Cited by 96 · see citing works
Macroautophagy and aging: The impact of cellular recycling on health and longevity
Nieto-Torres, J. L., & Hansen, M. (2021) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2021.101020 · Cited by 91 · see citing works
Aging shifts mitochondrial dynamics toward fission to promote germline stem cell loss.
Amartuvshin, O., Lin, C., Hsu, S., Kao, S., Chen, A., Tang, W., Chou, H., Chang, D., Hsu, Y., Hsiao, B., et al. (2020) · Aging Cell · doi:10.1111/acel.13191 · Cited by 75 · see citing works
Lu, Y., Regan, J. C., Eßer, J., Drews, L. F., Weinseis, T., Stinn, J., Hahn, O., Miller, R. A., Grönke, S., & Partridge, L. (2021) · eLife · doi:10.7554/elife.62233 · Cited by 73 · see citing works
Doing more with less: An integrative literature review on responsible consumption behaviour
Nangia, P., Bansal, S., & Thaichon, P. (2023) · Journal of Consumer Behaviour · doi:10.1002/cb.2163 · Cited by 77 · see citing works
Irazoki, A., Martínez‐Vicente, M., Aparicio, P., Aris, C., Alibakhshi, E., Rubio-Valera, M., Castellanos, J., Lores, L., Palacı́n, M., Gumà, A., et al. (2022) · Aging Cell · doi:10.1111/acel.13583 · Cited by 73 · see citing works
Neuronal induction of BNIP3-mediated mitophagy slows systemic aging in Drosophila
Schmid, E. T., Pyo, J.-H., & Walker, D. W. (2022) · Nature Aging · doi:10.1038/s43587-022-00214-y · Cited by 72 · see citing works
Self-citationProteostasis failure and mitochondrial dysfunction leads to aneuploidy-induced senescence
Joy, J., Barrio, L., Santos-Tapia, C., Romão, D., Giakoumakis, N. N., Clemente-Ruiz, M., & Milán, M. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.06.009 · Cited by 63 · see citing works
Lacombe, A., & Scorrano, L. (2024) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2024.02.001 · Cited by 64 · see citing works
Mitophagy in aging and longevity
Guo, J., & Chiang, W. (2021) · IUBMB Life · doi:10.1002/iub.2585 · Cited by 58 · see citing works
Guo, W., Vandoorne, T., Steyaert, J., Staats, K. A., & Bosch, L. V. D. (2020) · Brain · doi:10.1093/brain/awaa022 · Cited by 56 · see citing works
Molecular Mechanisms of Autophagy Decline during Aging
Lim, S. H. Y., Hansen, M., & Kumsta, C. (2024) · Cells · doi:10.3390/cells13161364 · Cited by 53 · see citing works
Martinez, A., Sánchez-Martínez, Á., Pickering, J. T., Twyning, M. J., Terriente-Félix, A., Chen, P., Chen, C., & Whitworth, A. J. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00701-3 · Cited by 52 · see citing works
Decreasing pdzd8-mediated mito–ER contacts improves organismal fitness and mitigates Aβ 42 toxicity
Hewitt, V. L., Miller‐Fleming, L., Twyning, M. J., Andreazza, S., Mattedi, F., Prudent, J., Polleux, F., Vagnoni, A., & Whitworth, A. J. (2022) · Life Science Alliance · doi:10.26508/lsa.202201531 · Cited by 44 · see citing works
Aedes aegypti Argonaute 2 controls arbovirus infection and host mortality
Dong, S., & Dimopoulos, G. (2023) · Nature Communications · doi:10.1038/s41467-023-41370-y · Cited by 45 · see citing works
Neuronal autophagy in the control of synapse function
Karpova, A., Hiesinger, P. R., Kuijpers, M., Albrecht, A., Kirstein, J., Andres‐Alonso, M., Biermeier, A. J., Eickholt, B. J., Mikhaylova, M., Maglione, M., et al. (2025) · Neuron · doi:10.1016/j.neuron.2025.01.019 · Cited by 46 · see citing works
Mitochondrial Contributions to Hematopoietic Stem Cell Aging
Morganti, C., & Ito, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222011117 · Cited by 46 · see citing works
The hunger strikes back: an epigenetic memory for autophagy
González-Rodríguez, P., Füllgrabe, J., & Joseph, B. (2023) · Cell Death and Differentiation · doi:10.1038/s41418-023-01159-4 · Cited by 41 · see citing works
Si, H., Ma, P., Liang, Q., Yin, Y., Wang, P., Zhang, Q., Wang, S., & Deng, H. (2019) · PLOS ONE · doi:10.1371/journal.pone.0225214 · Cited by 37 · see citing works
Accumulation of F-actin drives brain aging and limits healthspan in Drosophila
Schmid, E. T., Schinaman, J. M., Liu-Abramowicz, N., Williams, K. S., & Walker, D. W. (2024) · Nature Communications · doi:10.1038/s41467-024-53389-w · Cited by 34 · see citing works
Self-citationNanoparticles Induce Autophagy via mTOR Pathway Inhibition and Reactive Oxygen Species Generation
Lu, J. Q., Hao, S.-L., & Yang, W. (2020) · Nanomedicine · doi:10.2217/nnm-2019-0387 · Cited by 34 · see citing works
Mitophagy impairment in neurodegenerative diseases: Pathogenesis and therapeutic interventions
Mani, S., Swargiary, G., & Chadha, R. (2021) · Mitochondrion · doi:10.1016/j.mito.2021.01.001 · Cited by 32 · see citing works
Xu, F., Tautenhahn, H., Dirsch, O., & Dahmen, U. (2022) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-022-04074-2 · Cited by 31 · see citing works
Human Rights Here and Now: Celebrating the Universal Declaration of Human Rights.
Flowers, N. B. (1998) · Cited by 31 · see citing works
Aparício, R., Hansen, M., Walker, D. W., & Kumsta, C. (2020) · Autophagy · doi:10.1080/15548627.2020.1725404 · Cited by 31 · see citing works
Self-citationDas, S., Murumulla, L., Ghosh, P., & Challa, S. (2025) · BioMetals · doi:10.1007/s10534-025-00665-x · Cited by 31 · see citing works
Cai, X., Chen, S., Liang, J., Tang, M., & Wang, S. (2020) · Food and Chemical Toxicology · doi:10.1016/j.fct.2020.111965 · Cited by 30 · see citing works
Recent advances in understanding the role of proteostasis
Verma, K., Verma, M., Chaphalkar, A., & Chakraborty, K. (2021) · Faculty Reviews · doi:10.12703/r/10-72 · Cited by 31 · see citing works
p62 works as a hub modulation in the ageing process
Fan, X., Huang, T., Tong, Y., Fan, Z., Yang, Z., Yang, D., Mao, X., & Yang, M. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101538 · Cited by 29 · see citing works
Loss of STING in parkin mutant flies suppresses muscle defects and mitochondria damage
Moehlman, A. T., Kanfer, G., & Youle, R. J. (2023) · PLoS Genetics · doi:10.1371/journal.pgen.1010828 · Cited by 31 · see citing works
Zhang, L., Zheng, Y., Shao, M., Chen, A., Liu, M., Sun, W., Li, T., Fang, Y., Fang, Y., Shipeng, Z., et al. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107617 · Cited by 29 · see citing works
Bixin Protects Against Kidney Interstitial Fibrosis Through Promoting STAT6 Degradation
Li, J., Yang, Y., Wei, S., Chen, L., Xue, L., Tian, H., & Tao, S. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.576988 · Cited by 29 · see citing works
Hallmarks of aging: A user’s guide for comparative biologists
Biga, P. R., Duan, J. E., Young, T. E., Marks, J. R., Bronikowski, A. M., Decena-Segarra, L. P., Randolph, E. C., Pavuluri, A., Li, G., Fang, Y., et al. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102616 · Cited by 32 · see citing works
Proteostasis-associated aging: lessons from a Drosophila model
Yu, G., & Hyun, S. (2020) · Genes & Genomics · doi:10.1007/s13258-020-01012-9 · Cited by 29 · see citing works
Ardah, M. T., Eid, N. A. S., Kitada, T., & Haque, M. E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413398 · Cited by 28 · see citing works
Autophagy in Spinocerebellar Ataxia Type 3: From Pathogenesis to Therapeutics
Paulino, R., & Nóbrega, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087405 · Cited by 29 · see citing works
Mukherjee, S., Maddalena, M., Lü, Y., Martinez, S., Nataraj, N. B., Noronha, A., Sinha, S., Teng, K., Cohen‐Kaplan, V., Ziv, T., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2119644119 · Cited by 26 · see citing works
Dai, X., Zhang, Q., Zhang, G., Ma, C., & Zhang, R. (2023) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2023.120878 · Cited by 25 · see citing works
Role of Prohibitins in Aging and Therapeutic Potential Against Age-Related Diseases
Belser, M., & Walker, D. W. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.714228 · Cited by 26 · see citing works
Self-citationJiao, J., Curley, M., Graça, F. A., Robles‐Murguia, M., Shirinifard, A., Finkelstein, D., Xu, B., Fan, Y., & Demontis, F. (2023) · Cell Reports · doi:10.1016/j.celrep.2022.111970 · Cited by 24 · see citing works
Song, X., Aw, J. T. M., Ma, F., Cheung, M. F., Leung, D., & Herrup, K. (2021) · The Journal of Neuroscience · doi:10.1523/jneurosci.0845-21.2021 · Cited by 23 · see citing works
Autophagy, innate immunity, and cardiac disease
Santovito, D., Steffens, S., Barachini, S., & Madonna, R. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1149409 · Cited by 24 · see citing works
Chen, G., Zeng, L., Yan, F., Liu, J., Qin, M., Wang, F., & Zhang, X. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.919905 · Cited by 23 · see citing works
Zhang, Y., Ma, P., Wang, S., Chen, S., & Deng, H. (2025) · Nature Communications · doi:10.1038/s41467-025-60196-4 · Cited by 22 · see citing works
Zhao, X. L., Li, X., Shi, X., & Karpac, J. (2020) · Aging Cell · doi:10.1111/acel.13172 · Cited by 20 · see citing works
Pareek, G., & Pallanck, L. J. (2020) · PLoS Genetics · doi:10.1371/journal.pgen.1009118 · Cited by 22 · see citing works
Chang, R., Sun, X., Jia, H., Xu, Q., Dong, Z., Tang, Y. J., Luo, S., Jiang, Q., Loor, J. J., & Xu, C. (2022) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-022-00695-2 · Cited by 21 · see citing works
Hunt, L. C., Curley, M., Nyamkondiwa, K., Stephan, A., Jiao, J., Kavdia, K., Pagala, V., Peng, J., & Demontis, F. (2025) · PLoS Biology · doi:10.1371/journal.pbio.3002998 · Cited by 19 · see citing works
Bi-Directional Relationship Between Autophagy and Inflammasomes in Neurodegenerative Disorders
Panda, C., & Mahapatra, R. K. (2022) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-021-01184-2 · Cited by 19 · see citing works
Chang, R., Tang, Y. J., Jia, H., Dong, Z., Gao, S., Song, Q., Dong, H., Xu, Q., Jiang, Q., Loor, J. J., et al. (2022) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2022.11.044 · Cited by 19 · see citing works
Autophagy and UPS pathway contribute to nicotine-induced protection effect in Parkinson’s disease
Ullah, I., Uddin, S., Zhao, L., Wang, X., & Li, H.-Y. (2024) · Experimental Brain Research · doi:10.1007/s00221-023-06765-9 · Cited by 13 · see citing works
The strange case of Drp1 in autophagy: Jekyll and Hyde?
Chen, Y., Culetto, E., & Legouis, R. (2022) · BioEssays · doi:10.1002/bies.202100271 · Cited by 16 · see citing works
Autophagy and polyphenol intervention strategy in aging
Gu, Y., & Han, J. (2022) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2022.12.013 · Cited by 19 · see citing works
A neuroprotective role of Ufmylation through Atg9 in the aging brain of Drosophila
Li, H., Yu, Z., Niu, Z., Cheng, Y., Wei, Z., Cai, Y., Ma, F., Hu, L., Zhu, J., & Zhang, W. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04778-9 · Cited by 17 · see citing works
Drosophila as a Robust Model System for Assessing Autophagy: A Review
Demir, E., & Kacew, S. (2023) · Toxics · doi:10.3390/toxics11080682 · Cited by 17 · see citing works
Wu, C., Zhao, J., Wu, Q., Tan, Q., Liu, Q., & Xiao, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189728 · Cited by 17 · see citing works
Liao, Z., Gong, Z., Wang, Z., Yang, W., Liu, W., Hou, L., Liu, X., Hua, J., Wang, B., & Li, N. (2022) · Cells · doi:10.3390/cells11172706 · Cited by 17 · see citing works
Bhattacharjee, A., Ürmösi, A., Jipa, A., Kovács, L., Deák, P., Szabó, Á., & Juhász, G. (2022) · Autophagy · doi:10.1080/15548627.2022.2037852 · Cited by 17 · see citing works
Wang, J., Wen, D., Wang, S., Gao, Y., & Yin, X. (2023) · The FASEB Journal · doi:10.1096/fj.202301312r · Cited by 16 · see citing works
SQSTM1-mediated clearance of cytoplasmic mutant TARDBP/TDP-43 in the monkey brain
Yin, P., Bai, D., Deng, F., Zhang, C., Jia, Q., Zhu, L., Chen, L., Li, B., Guo, X., Ye, J., et al. (2021) · Autophagy · doi:10.1080/15548627.2021.2013653 · Cited by 16 · see citing works
Rani, L., Sahu, M. R., & Mondal, A. C. (2022) · Neuroscience · doi:10.1016/j.neuroscience.2022.07.007 · Cited by 16 · see citing works
Yang, X., Xu, J., Xu, Y., Wang, C., Lin, F., & Yu, J. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155434 · Cited by 15 · see citing works
Ma, C., Wang, Y., Zhang, G., & Dai, X. (2021) · Food Science & Nutrition · doi:10.1002/fsn3.2108 · Cited by 15 · see citing works
Lipid droplets modulate proteostasis, SQST-1/SQSTM1 dynamics, and lifespan in C. elegans
Kumar, A. V., Mills, J., Parker, W. M., Leitão, J. A., Rodriguez, D. I., Daigle, S. E., Ng, C., Patel, R., Aguilera, J. L., Johnson, J. R., et al. (2023) · iScience · doi:10.1016/j.isci.2023.107960 · Cited by 14 · see citing works
Walweel, N., & Aydin, O. (2024) · ACS Omega · doi:10.1021/acsomega.4c02234 · Cited by 16 · see citing works
Amponsah, P. S., Bökenkamp, J.-E., Kurpa, O., Lenhard, S., Myronova, A., Velazquez, D., Hirschelmann, C., Behrends, C., Herrmann, J. M., Räschle, M., et al. (2024) · bioRxiv · doi:10.1038/s41467-025-60857-4 · Cited by 15 · see citing works
Social perception of young adults prolongs the lifespan of aged Drosophila
Cho, L.-C., Yu, C.-C., & Kao, C.-F. (2021) · npj Aging and Mechanisms of Disease · doi:10.1038/s41514-021-00073-8 · Cited by 14 · see citing works
Lim, J. J., & Hyun, S. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112803 · Cited by 13 · see citing works
Lim, J. J., Noh, S., Kang, W., Hyun, B., Lee, B., & Hyun, S. (2024) · Autophagy · doi:10.1080/15548627.2024.2389607 · Cited by 11 · see citing works
The regulation of microglia by aging and autophagy in multiple sclerosis
Wang, X., Sun, Y., Yu, H., Xue, C., Pei, X., Chen, Y., & Guan, Y. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107786 · Cited by 11 · see citing works
Pan, S.-Y., Guo, S., Dai, J.-R., Gu, Y., Wang, G., Wang, Y., Qin, Z., & Luo, L. (2022) · Food Science and Human Wellness · doi:10.1016/j.fshw.2022.03.028 · Cited by 11 · see citing works
Quan, W., Sun, T., Hu, B., Luo, Q., Zhong, Y., Chen, W., & Tuo, Q. (2024) · Biomolecules · doi:10.3390/biom14101226 · Cited by 10 · see citing works
Yin, Z., Gong, G., Zhu, C., Wang, B., Sun, C., Liu, X., & Yin, J. (2020) · Neuroreport · doi:10.1097/wnr.0000000000001491 · Cited by 10 · see citing works
Selective autophagy: a therapeutic target for healthy aging?
Manastireanu, D. M., Salazar, N., Bejarano, E., & Nieto-Torres, J. L. (2024) · Aging Advances · doi:10.4103/agingadv.agingadv-d-24-00002 · Cited by 7 · see citing works
Du, X., Wang, Y., Wang, J., Liu, X., Chen, J., Kang, J., Yang, X., & Wang, H. (2022) · Experimental Gerontology · doi:10.1016/j.exger.2022.111856 · Cited by 8 · see citing works
Plasma cell biology: Foundations for targeted therapeutic development in transplantation
Rossi, A. P., Alloway, R. R., Hildeman, D. A., & Woodle, E. S. (2021) · Immunological Reviews · doi:10.1111/imr.13011 · Cited by 8 · see citing works
Toxicity of C9orf72 -associated dipeptide repeat peptides is modified by commonly used protein tags
Morón-Oset, J., Fischer, L. K., Carcolé, M., Giblin, A., Zhang, P., Isaacs, A. M., Grönke, S., & Partridge, L. (2023) · Life Science Alliance · doi:10.26508/lsa.202201739 · Cited by 7 · see citing works
Protein modification regulated autophagy in Bombyx mori and Drosophila melanogaster
Wu, W., Lin, L., Zhao, Y., Li, H., & Zhang, R. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1281555 · Cited by 7 · see citing works
Drosophila as a model to understand autophagy deregulation in human disorders
Denton, D., O’Keefe, L. V., & Kumar, S. (2020) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2020.01.005 · Cited by 7 · see citing works
Liu, H., Das, P. P., Zhang, J., Yu, L., Wang, M., Lin, Q., Zhou, Y., Xu, Q., & Wong, S. (2021) · Journal of Proteomics · doi:10.1016/j.jprot.2021.104314 · Cited by 7 · see citing works
Soft-Shelled Turtle Peptides Extend Lifespan and Healthspan in Drosophila
Wang, Q., Zhang, J., Zhuang, J., Shen, F., Zhao, M., Du, J., Yu, P., Zhong, H., & Feng, F. (2022) · Nutrients · doi:10.3390/nu14245205 · Cited by 5 · see citing works
Molecular mechanism on autophagy associated cardiovascular dysfunction in Drosophila melanogaster
Zhang, W., Zhou, R., Lei, X., Wang, M., Duan, Q., Miao, Y., Zhang, T., Li, X., Zutong, Z., Wang, L., et al. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1512341 · Cited by 5 · see citing works
Sheng, Y., Zhu, X., Wei, L., Zou, Y., Qi, X., Shi, R., Xu, W., Wang, X., Ding, G., & Duan, Y. (2024) · Aging · doi:10.18632/aging.205748 · Cited by 6 · see citing works
Effect on hypoxia/reoxygenation-induced cardiomyocyte injury and Pink1/Parkin pathway
Lu, X., Huang, G., Bao, H., Duan, Z., Li, C. R., Lin, M., Zhou, H., & Wei, Z. L. (2023) · General Physiology and Biophysics · doi:10.4149/gpb_2022045 · Cited by 4 · see citing works
Umekar, M. J., Qutub, M., Premchandani, T., Tatode, A., Taksansde, J., Singanwad, P., Kale, M. B., Maniyar, M. G., & Hussain, U. (2025) · Precision medication. · doi:10.1016/j.prmedi.2025.100051 · Cited by 3 · see citing works
- Authors
- Aparicio, R., Rana, A., & Walker, D. W.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Walker, David W.
- ORCID
- Walker, David W.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 28
- Issue
- 4
- Pages
- 1029-1040.e5
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6688777
- OpenAlex
- W2963984502
- Cited by
- 129
- References
- 55
- Citations by year
- 2026: 5 · 2025: 19 · 2024: 17 · 2023: 20 · 2022: 23 · 2021: 21 · 2020: 19 · 2019: 2 · 2018: 1
- FWCI
- 5.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute on Aging
- American Federation for Aging Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- p62, autophagy, aging, lifespan extension, healthspan, mitochondrial fission, mitophagy, mitochondrial homeostasis, proteostasis, Drosophila melanogaster
- MeSH terms
- Proteostasis, Animals, Autophagy, DNA-Binding Proteins, Drosophila melanogaster, Health, Longevity, Male, Mitochondria, Up-Regulation, Drosophila Proteins, Transcription Factor TFIID, TATA-Binding Protein Associated Factors, Mitophagy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
