Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging
Open accessAbstract
Aging causes a general decline in cellular metabolic activity, and function in different tissues and whole body homeostasis. However, the understanding about the metabolomic and autophagy changes in skeletal muscle and heart during aging is still limited. We thus examined markers for macroautophagy, chaperone-mediated autophagy (CMA), mitochondrial quality control, as well as cellular metabolites in skeletal and cardiac muscle from young (5 months old) and aged (27 months old) mice. We found decreased autophagic degradation of p62 and increased ubiquitinated proteins in both tissues from aged mice, suggesting a decline in macroautophagy during aging. In skeletal muscle from aged mice, there also was a decline in LC3B-I conjugation to phosphatidylethanolamine (PE) possibly due to decreased protein levels of ATG3 and ATG12-ATG5. The CMA markers, LAMP-2A and Hsc70, and mitochondrial turnover markers, Drp1, PINK1 and PGC1α also were decreased. Metabolomics analysis showed impaired β-oxidation in heart of aged mice, whereas increased branched-chain amino acids (BCAAs) and ceramide levels were found in skeletal muscle of aged mice that in turn, may contribute to insulin resistance in muscle. Taken together, our studies showed similar declines in macroautophagy but distinct effects on CMA, mitochondrial turnover, and metabolic dysfunction in muscle vs. heart during aging.
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?
In skeletal muscle, mitochondrial fission proteins are reduced in ageing sarcopenia, cancer cachexia, and chemotherapy-induced muscle wasting.
“In skeletal muscle the mitochondrial fission proteins are reduced in different physiopathological conditions including ageing sarcopenia, cancer cachexia and chemotherapy-induced muscle wasting.”
From DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass (2019) · cites this paper as [14]
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
1 retracted
Wenz, T., Rossi, S. G., Rotundo, R. L., Spiegelman, B. M., & Moraes, C. T. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911570106 · Cited by 600 · see citing works
RetractedAutophagy regulates lipid metabolism
Singh, R., Kaushik, S., Wang, Y., Xiang, Y., Novak, I., Komatsu, M., Tanaka, K., Cuervo, A. M., & Czaja, M. J. (2009) · Nature · doi:10.1038/nature07976 · Cited by 3,975 · see citing works
Mitochondrial Fission, Fusion, and Stress
Youle, R. J., & van der Bliek, A. M. (2012) · Science · doi:10.1126/science.1219855 · Cited by 3,674 · see citing works
Newgard, C. B., An, J., Bain, J. R., Muehlbauer, M. J., Stevens, R. D., Lien, L. F., Haqq, A. M., Shah, S. H., Arlotto, M., Slentz, C. A., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.02.002 · Cited by 3,165 · see citing works
Autophagy in Human Health and Disease
Choi, A. M. K., Ryter, S. W., & Levine, B. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1205406 · Cited by 2,583 · see citing works
Human gut microbes impact host serum metabolome and insulin sensitivity
Pedersen, H. K., Gudmundsdottir, V., Nielsen, H. B., Hyotylainen, T., Nielsen, T., Jensen, B. A. H., Forslund, K., Hildebrand, F., Prifti, E., Falony, G., et al. (2016) · Nature · doi:10.1038/nature18646 · Cited by 2,116 · see citing works
Extensive Involvement of Autophagy in Alzheimer Disease: An Immuno-Electron Microscopy Study
Nixon, R. A., Wegiel, J., Kumar, A., Yu, W. H., Peterhoff, C., Cataldo, A., & Cuervo, A. M. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/64.2.113 · Cited by 1,588 · see citing works
Autophagy in mammalian development and differentiation
Mizushima, N., & Levine, B. (2010) · Nature Cell Biology · doi:10.1038/ncb0910-823 · Cited by 1,555 · see citing works
The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress
Nakai, A., Yamaguchi, O., Takeda, T., Higuchi, Y., Hikoso, S., Taniike, M., Omiya, S., Mizote, I., Matsumura, Y., Asahi, M., et al. (2007) · Nature Medicine · doi:10.1038/nm1574 · Cited by 1,520 · see citing works
A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy
Lee, I. H., Cao, L., Mostoslavsky, R., Lombard, D. B., Liu, J., Bruns, N. E., Tsokos, M., Alt, F. W., & Finkel, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712145105 · Cited by 1,473 · see citing works
Autophagy is required to maintain muscle mass.
Masiero, E., Agatea, L., Mammucari, C., Blaauw, B., Loro, E., Komatsu, M., Metzger, D., Reggiani, C., Schiaffino, S., & Sandri, M. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.10.008 · Cited by 1,282 · see citing works
Molecular dissection of autophagy: two ubiquitin-like systems
Ohsumi, Y. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35056522 · Cited by 1,240 · cited 2× · see citing works
“There are two ubiquitinlike systems that play very important roles in LC3B lipidation [19].”
BackgroundThe Atg12-Atg5 Conjugate Has a Novel E3-like Activity for Protein Lipidation in Autophagy
Hanada, T., Noda, N. N., Satomi, Y., Ichimura, Y., Fujioka, Y., Takao, T., Inagaki, F., & Ohsumi, Y. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.c700195200 · Cited by 1,123 · cited 1× · see citing works
“2A and C), which have E2-like and E3-like enzyme activity for the LC3B lipidation process, respectively [29, 30].”
BackgroundCamacho-Pereira, J., Tarragó, M. G., Chini, C. C. S., Nin, V., Escande, C., Warner, G. M., Puranik, A. S., Schoon, R. A., Reid, J. M., Galina, A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.006 · Cited by 901 · see citing works
Ceramides in insulin resistance and lipotoxicity
Summers, S. A. (2005) · Progress in Lipid Research · doi:10.1016/j.plipres.2005.11.002 · Cited by 852 · see citing works
Chaperone-mediated autophagy: roles in disease and aging
Cuervo, A. M., & Wong, E. S. P. (2013) · Cell Research · doi:10.1038/cr.2013.153 · Cited by 850 · see citing works
Ceramide Content Is Increased in Skeletal Muscle From Obese Insulin-Resistant Humans
Adams, J. M., Pratipanawatr, T., Berria, R., Wang, E. L., DeFronzo, R. A., Sullards, M. C., & Mandarino, L. J. (2004) · Diabetes · doi:10.2337/diabetes.53.1.25 · Cited by 670 · see citing works
Age-related decline in chaperone-mediated autophagy
Cuervo, A. M., & Dice, J. F. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002102200 · Cited by 665 · see citing works
Schmitz-Peiffer, C., Craig, D. L., & Biden, T. J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.34.24202 · Cited by 592 · see citing works
Jang, C., Oh, S. F., Wada, S., Rowe, G. C., Liu, L., Chan, M. C., Rhee, J., Hoshino, A., Kim, B., Ibrahim, A., et al. (2016) · Nature Medicine · doi:10.1038/nm.4057 · Cited by 589 · see citing works
Interplay of LRRK2 with chaperone-mediated autophagy
Orenstein, S. J., Kuo, S.-H., Tasset, I., Arias, E., Koga, H., Fernandez-Carasa, I., Cortes, E., Honig, L. S., Dauer, W., Consiglio, A., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3350 · Cited by 588 · see citing works
The metabolic footprint of aging in mice
Houtkooper, R. H., Argmann, C., Houten, S. M., Cantó, C., Jeninga, E. H., Andreux, P. A., Thomas, C., Doenlen, R., Schoonjans, K., & Auwerx, J. (2011) · Scientific Reports · doi:10.1038/srep00134 · Cited by 528 · see citing works
Zhang, C., & Cuervo, A. M. (2008) · Nature Medicine · doi:10.1038/nm.1851 · Cited by 520 · see citing works
Tai, E. S., Tan, M. L. S., Stevens, R. D., Low, Y.-L., Muehlbauer, M. J., Goh, D. L. M., Ilkayeva, O., Wenner, B. R., Bain, J. R., Lee, J. J. M., et al. (2010) · Diabetologia · doi:10.1007/s00125-009-1637-8 · Cited by 471 · see citing works
Mitophagy is triggered by mild oxidative stress in a mitochondrial fission dependent manner
Frank, M., Duvezin-Caubet, S., Koob, S., Occhipinti, A., Jagasia, R., Petcherski, A., Ruonala, M. O., Priault, M., Salin, B., & Reichert, A. S. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.08.007 · Cited by 468 · see citing works
Inhibition of autophagy in the heart induces age-related cardiomyopathy
Taneike, M., Yamaguchi, O., Nakai, A., Hikoso, S., Takeda, T., Mizote, I., Oka, T., Tamai, T., Oyabu, J., Murakawa, T., et al. (2010) · Autophagy · doi:10.4161/auto.6.5.11947 · Cited by 450 · see citing works
Huffman, K. M., Shah, S. H., Stevens, R. D., Bain, J. R., Muehlbauer, M., Slentz, C. A., Tanner, C. J., Kuchibhatla, M., Houmard, J. A., Newgard, C. B., et al. (2009) · Diabetes Care · doi:10.2337/dc08-2075 · Cited by 410 · see citing works
Jaswal, J. S., Keung, W., Wang, W., Ussher, J. R., & Lopaschuk, G. D. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.01.015 · Cited by 396 · see citing works
Mitophagy is required for mitochondrial biogenesis and myogenic differentiation of C2C12 myoblasts
Sin, J., Andres, A. M., Taylor, D. J. R., Weston, T., Hiraumi, Y., Stotland, A., Kim, B. J., Huang, C., Doran, K. S., & Gottlieb, R. A. (2016) · Autophagy · doi:10.1080/15548627.2015.1115172 · Cited by 385 · see citing works
Transcriptional and epigenetic regulation of autophagy in aging
Lapierre, L. R., Kumsta, C., Sandri, M., Ballabio, A., & Hansen, M. (2015) · Autophagy · doi:10.1080/15548627.2015.1034410 · Cited by 339 · see citing works
Mitochondrial dysfunction in aging: Much progress but many unresolved questions
Payne, B. A. I., & Chinnery, P. F. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.022 · Cited by 335 · see citing works
Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy
Sinha, R. A., You, S.-H., Zhou, J., Siddique, M. M., Bay, B.-H., Zhu, X., Privalsky, M. L., Cheng, S.-Y., Stevens, R. D., Summers, S. A., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci60580 · Cited by 303 · see citing works
Self-citationMitochondria: a hub of redox activities and cellular distress control
Kakkar, P., & Singh, B. (2007) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-007-9520-8 · Cited by 258 · see citing works
Self-citationAll-you-can-eat: autophagy in neurodegeneration and neuroprotection
Jaeger, P. A., & Wyss‐Coray, T. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-16 · Cited by 175 · see citing works
Wing, S. S., Chiang, H. L., Goldberg, A. L., & Dice, J. F. (1991) · Biochemical Journal · doi:10.1042/bj2750165 · Cited by 154 · see citing works
Boyle, A., Shih, H., Hwang, J., Ye, J., Lee, B. K. H., Zhang, Y., Kwon, D., Jun, K., Zheng, D., Sievers, R., et al. (2011) · Experimental Gerontology · doi:10.1016/j.exger.2011.02.010 · Cited by 153 · see citing works
Yamada, Y., Suzuki, N. N., Hanada, T., Ichimura, Y., Kumeta, H., Fujioka, Y., Ohsumi, Y., & Inagaki, F. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611473200 · Cited by 151 · see citing works
Muscle sphingolipids during rest and exercise: a C18:0 signature for insulin resistance in humans
Bergman, B. C., Brozinick, J. T., Strauss, A., Bacon, S., Kerege, A., Bui, H. H., Sanders, P., Siddall, P., Wei, T., Thomas, M. K., et al. (2016) · Diabetologia · doi:10.1007/s00125-015-3850-y · Cited by 148 · see citing works
Suppression of Phosphoinositide 3-Kinase Prevents Cardiac Aging in Mice
Inuzuka, Y., Okuda, J., Kawashima, T., Kato, T., Niizuma, S., Tamaki, Y., Iwanaga, Y., Yoshida, Y., Kosugi, R., Watanabe-Maeda, K., et al. (2009) · Circulation · doi:10.1161/circulationaha.109.871137 · Cited by 144 · see citing works
Lesmana, R., Sinha, R. A., Singh, B. K., Zhou, J., Ohba, K., Wu, Y., Yau, W. W. Y., Bay, B., & Yen, P. M. (2015) · Endocrinology · doi:10.1210/en.2015-1632 · Cited by 97 · see citing works
Self-citationKotoulas, O. B., Kalamidas, S. A., & Kondomerkos, D. J. (2004) · Microscopy Research and Technique · doi:10.1002/jemt.20046 · Cited by 70 · see citing works
Autophagic response to a single bout of moderate exercise in murine skeletal muscle
Kim, Y.-A., Kim, Y. S., & Song, W. J. (2011) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-011-0135-x · Cited by 69 · see citing works
Cardiomyocyte ryanodine receptor degradation by chaperone-mediated autophagy
Pedrozo, Z., Torrealba, N., Fernández, C., Gatica, D., Toro, B., Quiroga, C., Rodriguez, A. E., Sánchez, G., Gillette, T. G., Hill, J. A., et al. (2013) · Cardiovascular Research · doi:10.1093/cvr/cvt029 · Cited by 63 · see citing works
Muscle-specificity of age-related changes in markers of autophagy and sphingolipid metabolism
Russ, D. W., Boyd, I. M., McCoy, K., & McCorkle, K. W. (2015) · Biogerontology · doi:10.1007/s10522-015-9598-4 · Cited by 35 · see citing works
Consitt, L. A., Koves, T. R., Muoio, D. M., Nakazawa, M., Newton, C. A., & Houmard, J. A. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.09.116 · Cited by 26 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Autophagy in health and disease: A comprehensive review
Saha, S., Panigrahi, D. P., Patil, S., & Bhutia, S. K. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.05.007 · Cited by 514 · see citing works
DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass
Favaro, G., Romanello, V., Varanita, T., Andrea Desbats, M., Morbidoni, V., Tezze, C., Albiero, M., Canato, M., Gherardi, G., De Stefani, D., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10226-9 · Cited by 398 · see citing works
Mitochondrial quality control mechanisms as molecular targets in cardiac ageing
Picca, A., Mankowski, R. T., Burman, J. L., Donisi, L., Js, K., Marzetti, E., & Leeuwenburgh, C. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0059-z · Cited by 393 · see citing works
Targeting autophagy in obesity: from pathophysiology to management
Zhang, Y., Sowers, J. R., & Ren, J. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0009-1 · Cited by 338 · see citing works
Mitochondria: Their relevance during oocyte ageing
van der Reest, J., Cecchino, G. N., Haigis, M. C., & Kordowitzki, P. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101378 · Cited by 253 · see citing works
Mitochondrial ROS-Modulated mtDNA: A Potential Target for Cardiac Aging
Quan, Y., Xin, Y.-G., Tian, G., Zhou, J.-T., & Liu, X.-J. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/9423593 · Cited by 188 · see citing works
Self-citationAutophagy in aging and longevity
Wong, S. Q., Kumar, A. V., Mills, J., & Lapierre, L. R. (2019) · Human Genetics · doi:10.1007/s00439-019-02031-7 · Cited by 204 · see citing works
Mitophagy, Mitochondrial Dynamics, and Homeostasis in Cardiovascular Aging
Wu, N. N., Zhang, Y., & Ren, J. T. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/9825061 · Cited by 196 · see citing works
Hepatic stellate cell senescence in liver fibrosis: Characteristics, mechanisms and perspectives
Zhang, M., Salas, S. S., Damba, T., Borghesan, M., Demaria, M., & Moshage, H. J. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111572 · Cited by 180 · see citing works
LAMP2A, LAMP2B and LAMP2C: similar structures, divergent roles
Qiao, L., Hu, J., Qiu, X., Wang, C., Peng, J., Zhang, C., Zhang, M., Lu, H., & Chen, W. (2023) · Autophagy · doi:10.1080/15548627.2023.2235196 · Cited by 174 · see citing works
Revuelta, M., & Matheu, A. (2017) · Aging Cell · doi:10.1111/acel.12655 · Cited by 146 · see citing works
Amino acids in the regulation of aging and aging-related diseases
Canfield, C.-A. E., & Bradshaw, P. C. (2019) · Translational Medicine of Aging · doi:10.1016/j.tma.2019.09.001 · Cited by 133 · see citing works
Mitochondrial dysfunction and skeletal muscle atrophy: Causes, mechanisms, and treatment strategies
Kubat, G. B., Bouhamida, E., Ülger, Ö., Türkel, İ., Pedriali, G., Ramaccini, D., Ekinci, Ö., Özerkliğ, B., Atalay, Ö., Patergnani, S., et al. (2023) · Mitochondrion · doi:10.1016/j.mito.2023.07.003 · Cited by 128 · see citing works
Pleiotropic Effects of mTOR and Autophagy During Development and Aging
Schmeißer, K., & Parker, J. A. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00192 · Cited by 117 · see citing works
Li, H., Slone, J. D., Fei, L., & Huang, T. (2019) · Cells · doi:10.3390/cells8060608 · Cited by 103 · see citing works
Mitophagy Receptors and Mediators: Therapeutic Targets in the Management of Cardiovascular Ageing
Ajoolabady, A., Aslkhodapasandhokmabad, H., Aghanejad, A., Zhang, Y., & Ren, J. T. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101129 · Cited by 103 · see citing works
Metabolic Stress, Autophagy, and Cardiovascular Aging: from Pathophysiology to Therapeutics
Ren, J. T., Sowers, J. R., & Zhang, Y. (2018) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2018.08.001 · Cited by 99 · see citing works
Dulac, M., Leduc‐Gaudet, J., Reynaud, O., Ayoub, M., Guérin, A., Finkelchtein, M., Hussain, S. N., & Gouspillou, G. (2020) · The Journal of Physiology · doi:10.1113/jp279802 · Cited by 90 · see citing works
Autophagy, its mechanisms and regulation: Implications in neurodegenerative diseases
Moloudizargari, M., Asghari, M. H., Ghobadi, E., Fallah, M., Rasouli, S., & Abdollahi, M. R. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.09.005 · Cited by 93 · see citing works
Inhibition of the Fission Machinery Mitigates OPA1 Impairment in Adult Skeletal Muscles
Romanello, V., Scalabrin, M., Albiero, M., Blaauw, B., Scorrano, L., & Sandri, M. (2019) · Cells · doi:10.3390/cells8060597 · Cited by 91 · see citing works
Cisplatin nephrotoxicity as a model of chronic kidney disease
Shi, M., McMillan, K. L., Wu, J., Gillings, N., Flores, B., Moe, O. W., & Hu, M. C. (2018) · Laboratory Investigation · doi:10.1038/s41374-018-0063-2 · Cited by 89 · see citing works
Frailty biomarkers under the perspective of geroscience: A narrative review
Gonçalves, R. S. D. S. A., Maciel, Á. C. C., Rolland, Y., Vellas, B. J., & Barreto, P. D. S. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101737 · Cited by 85 · see citing works
Progress and Challenges in Targeted Protein Degradation for Neurodegenerative Disease Therapy
Fang, Y., Wang, J., Zhao, M., Zheng, Q., Ren, C., Wang, Y., & Zhang, J. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00844 · Cited by 100 · see citing works
Liang, W., Moyzis, A. G., Lampert, M. A., Diao, R. Y., Najor, R. H., & Gustafsson, Å. B. (2020) · Aging Cell · doi:10.1111/acel.13187 · Cited by 80 · see citing works
Influence of Normal Aging on Brain Autophagy: A Complex Scenario
Loeffler, D. A. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00049 · Cited by 77 · see citing works
Mitochondria: The metabolic switch of cellular oncogenic transformation
Tan, Y. Q., Zhang, X., Zhang, S., Zhu, T., Garg, M., Lobie, P. E., & Pandey, V. (2021) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2021.188534 · Cited by 75 · see citing works
Mitophagy in maintaining skeletal muscle mitochondrial proteostasis and metabolic health with ageing
Drake, J. C., & Yan, Z. (2017) · The Journal of Physiology · doi:10.1113/jp274337 · Cited by 74 · see citing works
Urbina-Varela, R., Castillo, N., Videla, L. A., & del Campo, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207704 · Cited by 74 · see citing works
Wang, S., Ge, W., Harns, C., Meng, X., Zhang, Y., & Ren, J. T. (2018) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2018.04.009 · Cited by 71 · see citing works
Macroautophagy and Chaperone‐Mediated Autophagy in Heart Failure: The Known and the Unknown
Ghosh, R., & Pattison, J. S. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/8602041 · Cited by 69 · see citing works
Autophagy-related signaling pathways are involved in cancer (Review)
Chen, C., Gao, H., & Su, X. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.10142 · Cited by 65 · see citing works
The Aging Heart: Mitophagy at the Center of Rejuvenation
Liang, W., & Gustafsson, Å. B. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00018 · Cited by 62 · see citing works
Adiponectin improves insulin sensitivity via activation of autophagic flux
Ahlstrom, P. F. U., Rai, E., Chakma, S., Cho, H. H., Palanivel, R., & Sweeney, G. (2017) · Journal of Molecular Endocrinology · doi:10.1530/jme-17-0096 · Cited by 62 · see citing works
Aging-Related Ovarian Failure and Infertility: Melatonin to the Rescue
Reiter, R. J., Sharma, R., Romero, A., Manucha, W. A., Tan, D. X., Zuccari, D. A. P. D. C., & Chuffa, L. G. D. A. (2023) · Antioxidants · doi:10.3390/antiox12030695 · Cited by 57 · see citing works
Melatonin/Nrf2/NLRP3 Connection in Mouse Heart Mitochondria during Aging
Fernández‐Ortiz, M., Sayed, R. K. A., Fernández‐Martínez, J., Cionfrini, A., Aranda‐Martínez, P., Escames, G., de Haro, T., & Acuña-Castroviejo, D. (2020) · Antioxidants · doi:10.3390/antiox9121187 · Cited by 54 · see citing works
Decreased ovarian function and autophagy gene methylation in aging rats
Li, Q., Cai, M., Wang, J., Gao, Q., Guo, X., Jia, X., Xu, S., & Zhu, H. F. (2020) · Journal of Ovarian Research · doi:10.1186/s13048-020-0615-0 · Cited by 51 · see citing works
Autophagy—A key pathway for cardiac health and longevity
Woodall, B. P., & Gustafsson, Å. B. (2018) · Acta Physiologica · doi:10.1111/apha.13074 · Cited by 50 · see citing works
Sarcopenia: Tilting the Balance of Protein Homeostasis
Tan, K. T., Ang, S. T., & Tsai, S. (2019) · PROTEOMICS · doi:10.1002/pmic.201800411 · Cited by 49 · see citing works
Sligar, J., Debruin, D. A., Saner, N. J., Philp, A. M., & Philp, A. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00388.2021 · Cited by 49 · see citing works
Fuqua, J. D., Mere, C., Kronemberger, A., Blomme, J., Bae, D., Turner, K., Harris, M. P., Scudese, E., Edwards, M., Ebert, S. M., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201900766r · Cited by 48 · see citing works
Protein and Mitochondria Quality Control Mechanisms and Cardiac Aging
Ghosh, R., Vinod, V., Symons, J. D., & Boudina, S. (2020) · Cells · doi:10.3390/cells9040933 · Cited by 49 · see citing works
Intracellular to Interorgan Mitochondrial Communication in Striated Muscle in Health and Disease
Boardman, N. T., Trani, G., Scalabrin, M., Romanello, V., & Wüst, R. C. I. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad004 · Cited by 49 · see citing works
Muscle aging and sarcopenia: The pathology, etiology, and most promising therapeutic targets
Grima-Terrén, M., Campanario, S., Ramírez‐Pardo, I., Cisneros, A., Hong, X., Perdiguero, E., Serrano, A. L., Isern, J., & Muñoz‐Cánoves, P. (2024) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2024.101319 · Cited by 49 · see citing works
Vasilaki, A., Richardson, A. G., Remmen, H. V., Brooks, S. V., Larkin, L. M., McArdle, A., & Jackson, M. J. (2017) · The Journal of Physiology · doi:10.1113/jp274336 · Cited by 44 · see citing works
Impact of Chaperone-Mediated Autophagy in Brain Aging: Neurodegenerative Diseases and Glioblastoma
Auzmendi-Iriarte, J., & Matheu, A. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.630743 · Cited by 45 · see citing works
Mitochondrial Respiration and Energy Production Under Some Abiotic Stresses
Rad, S. A., Dehghanian, Z., Lajayer, B. A., Nobaharan, K., & Astatkie, T. (2021) · Journal of Plant Growth Regulation · doi:10.1007/s00344-021-10512-1 · Cited by 44 · see citing works
Elsayed, R., Elashiry, M., Liu, Y., Morandini, A. C., El-Awady, A., Elashiry, M. M., Hamrick, M., & Cutler, C. W. (2023) · Aging and disease · doi:10.14336/ad.2022.0623 · Cited by 40 · see citing works
Pratiwi, Y. S., Lesmana, R., Goenawan, H., Sylviana, N., Setiawan, I. B., Tarawan, V. M., Lestari, K., Abdulah, R., Dwipa, L., Purba, A., et al. (2018) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2018/2810840 · Cited by 40 · see citing works
Azuma, K., Ikeda, K., & Inoue, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093182 · Cited by 40 · see citing works
The role of mitochondrial-related nuclear genes in age-related common disease
Li, H., Slone, J. D., & Huang, T. (2020) · Mitochondrion · doi:10.1016/j.mito.2020.04.012 · Cited by 41 · see citing works
Moments in autophagy and disease: Past and present
Wen, X., Yang, Y., & Klionsky, D. J. (2021) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2021.100966 · Cited by 38 · see citing works
Oikawa, Y., Izumi, R., Koide, M., Hagiwara, Y., Kanzaki, M., Suzuki, N., Kikuchi, K., Matsuhashi, T., Akiyama, Y., Ichijo, M., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0231064 · Cited by 36 · see citing works
Chaperone-mediated autophagy: Advances from bench to bedside
Li, W., Nie, T., Xu, H., Yang, J. H., Yang, Q., & Mao, Z. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.05.010 · Cited by 36 · see citing works
Molecular Mechanisms Underlying Muscle Wasting in Huntington’s Disease
Bozzi, M., & Sciandra, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218314 · Cited by 36 · see citing works
Regulatory role of exercise-induced autophagy for sarcopenia
Liang, J., Zeng, Z., Zhang, Y., & Chen, N. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2019.110789 · Cited by 33 · see citing works
Aas, S. N., Hamarsland, H., Cumming, K. T., Rognlien, S. H., Aase, O. J., Nordseth, M., Karsrud, S., Godager, S., Tømmerbakke, D., Handegard, V., et al. (2019) · Experimental Gerontology · doi:10.1016/j.exger.2019.110687 · Cited by 34 · see citing works
When S -Nitrosylation Gets to Mitochondria: From Signaling to Age-Related Diseases
Montagna, C., Cirotti, C., Rizza, S., & Filomeni, G. (2020) · Antioxidants and Redox Signaling · doi:10.1089/ars.2019.7872 · Cited by 35 · see citing works
Decreased autophagy and fuel switching occur in a senescent hepatic cell model system
Singh, B. K., Tripathi, M., Sandireddy, R., Tikno, K., Zhou, J., & Yen, P. M. (2020) · Aging · doi:10.18632/aging.103740 · Cited by 32 · see citing works
Self-citationSpermine and spermidine reversed age-related cardiac deterioration in rats
Zhang, H., Wang, J., Li, L., Chai, N., Chen, Y., Wu, F., Zhang, W., Wang, L., Shi, S., Zhang, L., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.18334 · Cited by 31 · see citing works
Le, Y.-C., Zhang, S., Ni, J.-H., You, Y., Luo, K., Yu, Y.-Q., & Shen, X. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0719-2 · Cited by 29 · see citing works
Yang, Q., Zhou, Y., Yin, H., Li, H., Zhou, M., Sun, G., Cao, Z., Man, R., Wang, H., & Li, J. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00403 · Cited by 31 · see citing works
Anti-Aging Effect of Metformin: A Molecular and Therapeutical Perspective
Torres, W., Nava, M., Galbán, N., Gómez, Y., Morillo, V., Rojas, M., Cano, C., Chacín, M., D’Marco, L., Herazo-Beltrán, Y., et al. (2020) · Current Pharmaceutical Design · doi:10.2174/1381612826666200716161610 · Cited by 28 · see citing works
Cho, J. M., Park, S., Ghosh, R., Ly, K., Ramous, C., Thompson, L., Hansen, M., Mattera, M. S. D. L. C., Pires, K. M. P., Ferhat, M., et al. (2021) · Aging Cell · doi:10.1111/acel.13467 · Cited by 27 · see citing works
Aging, Osteo-Sarcopenia, and Musculoskeletal Mechano-Transduction
Leser, J. M., Harriot, A. D., Buck, H., Ward, C. W., & Stains, J. P. (2021) · Frontiers in Rehabilitation Sciences · doi:10.3389/fresc.2021.782848 · Cited by 27 · see citing works
He, X., Liu, J.-K., & Zang, W.-J. (2021) · Free Radical Biology & Medicine · doi:10.1016/j.freeradbiomed.2021.12.255 · Cited by 27 · see citing works
Wang, Y., Li, J., Zhang, Z., Wang, R., Hai, B., & Zhang, Y. (2023) · Life · doi:10.3390/life13041006 · Cited by 28 · see citing works
Endoplasmic reticulum stress and mitochondrial dysfunction during aging: Role of sphingolipids
Chen, Q., Kovilakath, A., Allegood, J. C., Thompson, J., Hu, Y., Cowart, L. A., & Lesnefsky, E. J. (2023) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2023.159366 · Cited by 26 · see citing works
Nichenko, A. S., Sorensen, J. R., Southern, W. M., Qualls, A., Schifino, A. G., McFaline‐Figueroa, J., Blum, J., Tehrani, K. F., Yin, H., Mortensen, L. J., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041937 · Cited by 26 · see citing works
Huang, J., & Wang, J. (2024) · Molecular Medicine Reports · doi:10.3892/mmr.2024.13378 · Cited by 27 · see citing works
Perkins, G. A., Lee, J. H., Park, S., Kang, M., Perez-Flores, M. C., Ju, S., Phillips, G. W., Lysakowski, A., Gratton, M. A., & Yamoah, E. N. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.2901-19.2020 · Cited by 24 · see citing works
Age-related decline of chaperone-mediated autophagy in skeletal muscle leads to progressive myopathy
Santiago‐Fernández, O., Coletto, L., Tasset, I., Kaushik, S., Concepcion, A. R., Qaisar, R., Macho-González, A., Lindenau, K. L., Díaz, A., Khawaja, R. R., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01412-9 · Cited by 23 · see citing works
Oxytocin promotes hepatic regeneration in elderly mice
Luo, D., Jin, B., Zhai, X., Li, J., Liu, C., Guo, W., & Li, J. (2021) · iScience · doi:10.1016/j.isci.2021.102125 · Cited by 22 · see citing works
Kim, K. W., Cho, H., Khaliq, S. A., Son, K. H., & Yoon, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21082862 · Cited by 21 · see citing works
Mitochondrial Adaptations in the Growing Heart
Sánchez-Díaz, M., Nicolás-Ávila, J. Á., Cordero, M. D., & Hidalgo, A. (2020) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2020.01.006 · Cited by 21 · see citing works
Polyamines and Physical Activity in Musculoskeletal Diseases: A Potential Therapeutic Challenge
Galasso, L., Cappella, A., Mulè, A., Castelli, L., Ciorciari, A. M., Stacchiotti, A., & Montaruli, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24129798 · Cited by 23 · see citing works
Marini, C., Cossu, V., Bonifacino, T., Bauckneht, M., Torazza, C., Bruno, S., Castellani, P., Ravera, S., Milanese, M., Venturi, C. B., et al. (2020) · EJNMMI Research · doi:10.1186/s13550-020-00666-6 · Cited by 20 · see citing works
Booth, L. K., Redgrave, R. E., Tual‐Chalot, S., Spyridopoulos, I., Phillips, H. M., & Richardson, G. D. (2023) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-031-26576-1_4 · Cited by 20 · see citing works
The Role of Chaperone-Mediated Autophagy in Bortezomib Resistant Multiple Myeloma
Nikesitch, N., Rebeiro, P., Ho, L. L., Pothula, S. P., Wang, X. M., Khong, T. T., Quek, H., Spencer, A. G., Lee, C. S., Roberts, T. L., et al. (2021) · Cells · doi:10.3390/cells10123464 · Cited by 19 · see citing works
Hao, J., Xi, Y., Jiao, L., Wen, X., Wu, R., Chang, G., Sun, F., Wei, C., & Li, H. (2022) · Cellular Signalling · doi:10.1016/j.cellsig.2022.110465 · Cited by 17 · see citing works
Iron status and oxidative stress in the aged rabbit heart
Lapenna, D., Ciofani, G., Pierdomenico, S. D., Giamberardino, M. A., & Porreca, E. (2017) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2017.11.016 · Cited by 17 · see citing works
Lee, M. J.-C., Saner, N. J., Ferri, A., García-Domínguez, E., Broatch, J. R., & Bishop, D. J. (2024) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2024.101272 · Cited by 16 · see citing works
Do, Y., Yagi, M., Hirai, H., Miki, K., Fukahori, Y., Setoyama, D., Yamamoto, M., Furukawa, T., Kunisaki, Y., Kang, D., et al. (2024) · Bioscience Reports · doi:10.1042/bsr20231992 · Cited by 16 · see citing works
Collagen VI Null Mice as a Model for Early Onset Muscle Decline in Aging
Capitanio, D., Moriggi, M., Palma, S. D., Bizzotto, D., Molon, S., Torretta, E., Fania, C., Bonaldo, P., Gelfi, C., & Braghetta, P. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00337 · Cited by 16 · see citing works
Li, C., White-Springer, S. H., Warren, L. K., & Wohlgemuth, S. E. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.11.022 · Cited by 16 · see citing works
Metabolism of sleep and aging: Bridging the gap using metabolomics
Sengupta, A., & Weljie, A. M. (2018) · Nutrition and Healthy Aging · doi:10.3233/nha-180043 · Cited by 16 · see citing works
Magalhães, S., Almeida, I., Martins, F., Camões, F., Soares, A. R., Goodfellow, B. J., Rebelo, S., & Nunes, A. (2021) · Molecules · doi:10.3390/molecules26216410 · Cited by 14 · see citing works
Functional alterations and transcriptomic changes during zebrafish cardiac aging
Shao, X., Fu, Y., Ma, J., Li, X., Lu, C., & Zhang, R. (2020) · Biogerontology · doi:10.1007/s10522-020-09881-z · Cited by 14 · see citing works
Chaperone Proteins: The Rising Players in Muscle Atrophy
Acquarone, D., Bertero, A., Brancaccio, M., & Sorge, M. (2024) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13659 · Cited by 13 · see citing works
Metabolomic Profiling of End-Stage Heart Failure Secondary to Chronic Chagas Cardiomyopathy
Díaz, M. L., Burgess, K. E., Burchmore, R., Gómez, M. A., Gómez‐Ochoa, S. A., Echeverría, L. E., Morillo, C. A., & González, C. I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810456 · Cited by 13 · see citing works
Age and sex-specific changes in mitochondrial quality control in skeletal and cardiac muscle
Springer, C. B., Ogbara, O., Silva, M. C. D., Henderson, A., Liu, Y., Prior, S. J., & Kuzmiak‐Glancy, S. (2025) · Frontiers in Aging · doi:10.3389/fragi.2025.1606110 · Cited by 13 · see citing works
Chen, Q., Huang, W., Çapanoğlu, E., Amrouche, A. T., & Lu, B. (2023) · Food Frontiers · doi:10.1002/fft2.261 · Cited by 12 · see citing works
Hypertrophic cardiomyopathy in MYBPC3 carriers in aging
Ananthamohan, K., Stelzer, J. E., & Sadayappan, S. (2024) · The Journal of Cardiovascular Aging · doi:10.20517/jca.2023.29 · Cited by 13 · see citing works
Chaperone-mediated autophagy as a modulator of aging and longevity
Endicott, S. J. (2024) · Frontiers in Aging · doi:10.3389/fragi.2024.1509400 · Cited by 12 · see citing works
Wu, H., Jang, J., Dridi, S., Ferrando, A. A., Wolfe, R. R., Kim, I., & Baum, J. (2020) · Physiological Reports · doi:10.14814/phy2.14575 · Cited by 10 · see citing works
Targeting Chaperone-Mediated Autophagy for Disease Therapy
Li, W., Dou, J., Yang, J., Xu, H., & She, H. (2018) · Current Pharmacology Reports · doi:10.1007/s40495-018-0138-1 · Cited by 10 · see citing works
Heat and mitochondrial bioenergetics
Schulze, A. T. V., & Geiger, P. C. (2022) · Current Opinion in Physiology · doi:10.1016/j.cophys.2022.100553 · Cited by 10 · see citing works
Noguchi, M., Kitakaze, T., Kobayashi, Y., Mukai, K., Harada, N., & Yamaji, R. (2020) · Nutrients · doi:10.3390/nu12082180 · 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
Cumming, K. T., Kvamme, N. H., Schaad, L., Ugelstad, I., & Raastad, T. (2021) · European Journal of Applied Physiology · doi:10.1007/s00421-021-04633-4 · Cited by 9 · see citing works
Russ, D. W., Garvey, S. M., Densmore, C., Hawks, T., Herman, S., & Pardi, K. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2018.08.001 · Cited by 8 · see citing works
- Authors
- Zhou, J., Chong, S. Y., Lim, A., Singh, B. K., Sinha, R. A., Salmon, A. B., & Yen, P. M.
- Affiliations
- National University of Singapore (SG)
- Nanyang Technological University (SG)
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Yen, Paul M.
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2017-02-26
- Volume
- 9
- Issue
- 2
- Pages
- 583-599
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC5361683
- OpenAlex
- W2590970381
- Cited by
- 126
- References
- 45
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 8 · 2023: 11 · 2022: 9 · 2021: 18 · 2020: 27 · 2019: 13 · 2018: 16 · 2017: 9
- FWCI
- 13.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by
- Locations
- Aging (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- DR-NTU (Nanyang Technological University) (submittedVersion, other-oa)
- Funders
- American Heart Association (15BGIA23220016)
- Duke-NUS Medical School
- Medical Research Council
- National Medical Research Council (CIRG/1340/2012, NMRC/CIRG/ 1340/2012)
- National Institute on Aging (R01AG050797, P30AG013319)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- macroautophagy, chaperone-mediated autophagy, mitochondrial metabolism, skeletal muscle, myocardium, autophagy
- MeSH terms
- Aging, Animals, Autophagy, Energy Metabolism, Lysosomes, Mitochondria, Myocardium, Biomarkers, Muscle, Skeletal, Molecular Chaperones, Mice
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
