Role of PGC-1α in sarcopenia: Etiology and potential intervention—A mini-review
Abstract
Sarcopenia is age-associated deterioration of muscle mass and function caused by a wide scope of physiological and pathological changes ranging from hormonal disorders to loss of subcellular homeostasis. Recent research indicates that mitochondrial dysregulation with advanced age plays a central role in the development of sarcopenia due to the multifactorial functions of this organelle in energy supply, redox regulation, crosstalk with nuclear gene expression and apoptosis. In order to fulfill these roles, it is crucial that mitochondria maintain their own structural and functional integrity through biogenesis, antioxidant defense, fusion/fission dynamics and autophagy (mitophagy). Unfortunately, mitochondria undergo age-associated changes that compromise the above-mentioned properties that eventually contribute to the development of sarcopenia. The peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is involved in the transcriptional regulation of numerous nuclear and mitochondrial gene products participating in the cellular events that control muscle mass and function. Thus, it is not surprising that maintaining an optimal intracellular PGC-1α level and signaling activity is crucial in protecting the muscle from many degradative and destructive processes, such as proteolysis, oxidative damage, inflammation, uncontrolled autophagy and apoptosis. Physical exercise is a powerful stimulus to PGC-1α expression and signaling. Recent research indicates that PGC-1α-controlled mitochondrial biogenesis is not limited by old age per se and that elderly individuals can still benefit from increased muscular activity in terms of skeletal muscle health that ultimately contributes to quality of life in old age.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
PGC-1α, regulated by exercise training, is a pivotal transcriptional regulator in mitochondrial biogenesis, impacting muscle morphology and physiological function.
“PGC-1α, regulated by exercise training, serves as a pivotal transcriptional regulator in mitochondrial biogenesis, impacting muscle morphology and physiological function [48,49].”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [49]
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
RetractedWu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., Troy, A., Cinti, S., Lowell, B., Scarpulla, R. C., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80611-x · Cited by 4,139 · see citing works
Wallace, D. C. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095751 · Cited by 3,185 · see citing works
St-Pierre, J., Drori, S., Uldry, M., Silvaggi, J. M., Rhee, J., Jäger, S., Handschin, C., Zheng, K., Lin, J., Yang, W., et al. (2006) · Cell · doi:10.1016/j.cell.2006.09.024 · Cited by 2,233 · see citing works
Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging
Kujoth, G. C., Hiona, A., Pugh, T. D., Someya, S., Panzer, K., Wohlgemuth, S. E., Hofer, T., Seo, A. Y., Sullivan, R., Jobling, W. A., et al. (2005) · Science · doi:10.1126/science.1112125 · Cited by 2,165 · see citing works
FoxO3 Controls Autophagy in Skeletal Muscle In Vivo
Mammucari, C., Milan, G., Romanello, V., Masiero, E., Rudolf, R., Del Piccolo, P., Burden, S. J., Di Lisi, R., Sandri, C., Zhao, J., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.001 · Cited by 1,953 · see citing works
Autophagy: molecular machinery for self-eating
Yorimitsu, T., & Klionsky, D. J. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401765 · Cited by 1,540 · see citing works
Aging of skeletal muscle: a 12-yr longitudinal study
Frontera, W. R., Hughes, V. A., Fielding, R. A., Fiatarone, M. A., Evans, W. J., & Roubenoff, R. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.4.1321 · Cited by 1,443 · see citing works
PGC-1 coactivators: inducible regulators of energy metabolism in health and disease
Finck, B. N. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27794 · Cited by 1,427 · see citing works
Decline in skeletal muscle mitochondrial function with aging in humans
Short, K. R., Bigelow, M. L., Kahl, J., Singh, R., Coenen-Schimke, J., Raghavakaimal, S., & Nair, K. S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501559102 · Cited by 1,333 · see citing works
Mitochondria and the Autophagy–Inflammation–Cell Death Axis in Organismal Aging
Green, D. R., Galluzzi, L., & Kroemer, G. (2011) · Science · doi:10.1126/science.1201940 · Cited by 1,245 · see citing works
The role of exercise and PGC1α in inflammation and chronic disease
Handschin, C., & Spiegelman, B. M. (2008) · Nature · doi:10.1038/nature07206 · Cited by 1,083 · see citing works
SIRT1 Functionally Interacts with the Metabolic Regulator and Transcriptional Coactivator PGC-1α
Nemoto, S., Fergusson, M. M., & Finkel, T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501485200 · Cited by 1,047 · see citing works
Skeletal Muscle Strength as a Predictor of All-Cause Mortality in Healthy Men
Metter, E. J., Talbot, L. A., Schrager, M., & CONWIT, R. A. (2002) · The Journals of Gerontology Series A · doi:10.1093/gerona/57.10.b359 · Cited by 843 · see citing works
Signaling in Muscle Atrophy and Hypertrophy
Sandri, M. (2008) · Physiology · doi:10.1152/physiol.00041.2007 · Cited by 830 · see citing works
Akimoto, T., Pohnert, S. C., Li, P., Zhang, M., Gumbs, C., Rosenberg, P. B., Williams, R. S., & Yan, Z. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m408862200 · Cited by 714 · see citing works
A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy
Ruas, J. L., White, J. P., Rao, R. R., Kleiner, S., Brannan, K. T., Harrison, B. C., Greene, N. P., Wu, J., Estall, J. L., Irving, B. A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.10.050 · Cited by 677 · see citing works
Mitochondrial dysfunction and sarcopenia of aging: from signaling pathways to clinical trials
Marzetti, E., Calvani, R., Cesari, M., Buford, T. W., Lorenzi, M., Behnke, B. J., & Leeuwenburgh, C. (2013) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2013.06.024 · Cited by 627 · see citing works
Metabolic adaptations through the PGC‐1α and SIRT1 pathways
Rodgers, J. T., Lerín, C., Gerhart‐Hines, Z., & Puigserver, P. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.11.034 · Cited by 599 · see citing works
Endurance Exercise as a Countermeasure for Aging
Lanza, I. R., Short, D. K., Short, K. R., Raghavakaimal, S., Basu, R., Joyner, M. J., McConnell, J. P., & Nair, K. S. (2008) · Diabetes · doi:10.2337/db08-0349 · Cited by 582 · see citing works
St‐Pierre, J., Lin, J. D., Krauss, S., Tarr, P. T., Yang, R., Newgard, C. B., & Spiegelman, B. M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301850200 · Cited by 543 · see citing works
Review Article: Sarcopenia: Causes, Consequences, and Preventions
Marcell, T. J. (2003) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/58.10.m911 · Cited by 536 · see citing works
Mitochondrial function and apoptotic susceptibility in aging skeletal muscle
Chabi, B., Ljubicic, V., Menzies, K. J., Huang, J. H., Saleem, A., & Hood, D. A. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2007.00347.x · Cited by 437 · see citing works
Sirtuins: The ‘ <i>magnificent seven</i> ’, function, metabolism and longevity
Dali‐Youcef, N., Lagouge, M., Froelich, S., Koehl, C., Schoonjans, K., & Auwerx, J. (2007) · Annals of Medicine · doi:10.1080/07853890701408194 · Cited by 402 · see citing works
Intracellular signaling during skeletal muscle atrophy
Kandarian, S. C., & Jackman, R. W. (2005) · Muscle & Nerve · doi:10.1002/mus.20442 · Cited by 393 · see citing works
Skeletal muscle apoptosis, sarcopenia and frailty at old age
Marzetti, E., & Leeuwenburgh, C. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.08.011 · Cited by 346 · see citing works
Skeletal muscle contractile and noncontractile components in young and older women and men
Kent‐Braun, J. A., Ng, A. V., & Young, K. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.2.662 · Cited by 338 · see citing works
Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy
Calvani, R., Joseph, A.-M., Adhihetty, P. J., Miccheli, A., Bossola, M., Leeuwenburgh, C., Bernabei, R., & Marzetti, E. (2013) · bchm · doi:10.1515/hsz-2012-0247 · Cited by 328 · see citing works
PGC-1, a versatile coactivator
Knutti, D., & Kralli, A. (2001) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(01)00457-x · Cited by 294 · see citing works
Williamson, D., Gallagher, P. M., Harber, M. P., Hollon, C. J., & Trappe, S. W. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2002.036673 · Cited by 290 · see citing works
Exercise alters SIRT1, SIRT6, NAD and NAMPT levels in skeletal muscle of aged rats
Koltai, E., Szabo, Z., Atalay, M., Boldogh, I., Naito, H., Goto, S., Nyakas, C., & Radak, Z. (2010) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2009.11.002 · Cited by 283 · see citing works
The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity
Hanai, J., Cao, P., Tanksale, P., Imamura, S., Koshimizu, E., Zhao, J., Kishi, S., Yamashita, M., Phillips, P. S., Sukhatme, V. P., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32741 · Cited by 281 · see citing works
Yoon, Y., Yoon, D., Lim, I. K., Yoon, S., Chung, H., Rojo, M., Malka, F., Jou, M., Martinou, J., & Yoon, G. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20753 · Cited by 275 · see citing works
Skeletal muscle aging and the mitochondrion
Johnson, M. L., Robinson, M. M., & Nair, K. S. (2013) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.12.003 · Cited by 233 · see citing works
Kang, C., OʼMoore, K. M., Dickman, J. R., & Ji, L. L. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.08.007 · Cited by 204 · see citing works
Self-citationEisele, P. S., Salatino, S., Sobek, J., Hottiger, M. O., & Handschin, C. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.375253 · Cited by 187 · see citing works
Álvarez-Guardia, D., Palomer, X., Coll, T., Davidson, M. M., Chan, T. O., Feldman, A. M., Laguna, J. C., & Vázquez‐Carrera, M. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq080 · Cited by 187 · see citing works
Mitochondrial Fusion Is Increased by the Nuclear Coactivator PGC-1β
Liesa, M., Borda-d'Agua, B., Medina‐Gómez, G., Lelliott, C. J., Paz, J. C., Rojo, M., Palacı́n, M., Vidal‐Puig, A., & Zorzano, A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003613 · Cited by 175 · see citing works
Mitochondrial death effectors: Relevance to sarcopenia and disuse muscle atrophy
Marzetti, E., Hwang, J. C. Y., Lees, H. A., Wohlgemuth, S. E., Dupont-Versteegden, E. E., Carter, C. S., Bernabei, R., & Leeuwenburgh, C. (2010) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.05.007 · Cited by 174 · see citing works
Kang, C., Chung, E., Diffee, G., & Ji, L. L. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2013.08.004 · Cited by 174 · see citing works
Oxidative Modification of Proteins: Age-Related Changes
Chakravarti, B., & Chakravarti, D. N. (2006) · Gerontology · doi:10.1159/000097865 · Cited by 172 · see citing works
Ljubicic, V., Joseph, A.-M., Saleem, A., Uguccioni, G., Collu-Marchese, M., Lai, R. Y. J., Nguyen, L. M.-D., & Hood, D. A. (2010) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.07.031 · Cited by 167 · see citing works
Gordon, J. W., Rungi, A. A., Inagaki, H., & Hood, D. A. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.90.1.389 · Cited by 160 · see citing works
Derbré, F., Gómez‐Cabrera, M. C., Nascimento, A. L. R., Sanchis‐Gomar, F., Martinez-Bello, V. E., Tresguerres, J. A. F., Fuentes, T., Gratas‐Delamarche, A., Monsalve, M., & Viña, J. (2011) · AGE · doi:10.1007/s11357-011-9264-y · Cited by 129 · see citing works
Ghosh, S., Lertwattanarak, R., Lefort, N., Molina-Carrion, M., Joya-Galeana, J., Bowen, B. P., Garduno-Garcia, J. D. J., Abdul-Ghani, M., Richardson, A., DeFronzo, R. A., et al. (2011) · Diabetes · doi:10.2337/db11-0121 · Cited by 128 · see citing works
Aging impairs insulin-stimulated glucose uptake in rat skeletal muscle via suppressing AMPKα
Wan, Q., Weiqiang, K., Zhu, Q., Pengju, Z., & Liu, Y. (2007) · Experimental & Molecular Medicine · doi:10.1038/emm.2007.59 · Cited by 113 · see citing works
Vercauteren, K., Pasko, R. A., Gleyzer, N., Marino, V. M., & Scarpulla, R. C. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00585-06 · Cited by 109 · see citing works
Mitochondrial damage and intralysosomal degradation in cellular aging
Terman, A., Gustafsson, B., & Brunk, U. T. (2006) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2006.08.006 · Cited by 103 · see citing works
Geng, T., Li, P., Yin, X., & Yan, Z. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2011.01.005 · Cited by 90 · see citing works
Kang, C., & Ji, L. L. (2013) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01354.2012 · Cited by 71 · see citing works
Self-citationMitochondrial biogenesis and angiogenesis in skeletal muscle of the elderly
Iversen, N., Krustrup, P., Rasmussen, H., Rasmussen, U. F., Saltin, B., & Pilegaard, H. (2011) · Experimental Gerontology · doi:10.1016/j.exger.2011.03.004 · Cited by 66 · see citing works
Hornberger, T., Mateja, R., Chin, E. R., Andrews, J., & Esser, K. (2005) · Journal of applied physiology · doi:10.1152/japplphysiol.00870.2004 · Cited by 62 · see citing works
Endurance exercise as a countermeasure for aging. Diabetes 2008;57:2933–2942
Lanza, I. R., Short, D. C., Short, K., Raghavakaimal, S., Basu, R., Mj, J., McConnell, J. P., & Nair, K. (2012) · Diabetes · doi:10.2337/db12-er10 · Cited by 37 · see citing works
Feng, H., Kang, C., Dickman, J. R., Koenig, R. T., Awoyinka, I., Zhang, Y., & Ji, L. L. (2012) · Experimental Physiology · doi:10.1113/expphysiol.2012.069286 · Cited by 34 · see citing works
Self-citationGouspillou, G., Picard, M. A., Godin, R., Burelle, Y., & Hepple, R. T. (2013) · Longevity & Healthspan · doi:10.1186/2046-2395-2-13 · Cited by 29 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Sarcopenia: Aging-Related Loss of Muscle Mass and Function
Larsson, L., Degens, H., Li, M., Salviati, L., Lee, Y. I., Thompson, W., Kirkland, J. L., & Sandri, M. (2019) · Physiological Reviews · doi:10.1152/physrev.00061.2017 · Cited by 1,797 · see citing works
Unravelling the mechanisms regulating muscle mitochondrial biogenesis
Hood, D. A., Tryon, L. D., Carter, H. N., Kim, Y., & Chen, C. C. W. (2016) · Biochemical Journal · doi:10.1042/bcj20160009 · Cited by 159 · see citing works
Impaired proteostasis during skeletal muscle aging
Fernando, R., Drescher, C., Nowotny, K., Grune, T., & Castro, J. P. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.08.037 · Cited by 134 · see citing works
Börsch, A., Ham, D. J., Mittal, N., Tintignac, L. A., Migliavacca, E., Feige, J. N., Rüegg, M. A., & Zavolan, M. (2021) · Communications Biology · doi:10.1038/s42003-021-01723-z · Cited by 85 · see citing works
Kim, J. C., Kang, Y. S., Noh, E. B., Seo, B. W., Seo, D. Y., Park, G. D., & Kim, S. H. (2018) · The Korean Journal of Physiology & Pharmacology · doi:10.4196/kjpp.2018.22.4.427 · Cited by 36 · see citing works
Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis
Wang, J., Jia, D., Zhang, Z., & Wang, D. (2025) · Metabolites · doi:10.3390/metabo15010059 · Cited by 23 · see citing works
- Authors
- Ji, L. L., & Kang, C.
- Affiliations
- University of Minnesota (US)
- Venue
- Gerontology
- Publisher
- S. Karger AG
- Published
- 2014-12-06
- Volume
- 61
- Issue
- 2
- Pages
- 139-148
- ISSN
- 0304-324X (ISSN-L)
- 1423-0003
- OpenAlex
- W2013828119
- Cited by
- 77
- References
- 55
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 9 · 2023: 6 · 2022: 7 · 2021: 13 · 2020: 9 · 2019: 4 · 2018: 7 · 2017: 3 · 2016: 5 · 2015: 2
- FWCI
- 0.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- sarcopenia, PGC-1α, mitochondrial dysfunction, mitochondrial biogenesis, mitophagy, mitochondrial fission and fusion, oxidative stress, skeletal muscle aging, physical activity, apoptosis, autophagy, inflammation, transcriptional regulation, muscle mass and function
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Aged, Aging, Heat-Shock Proteins, Humans, Mitochondria, Transcription Factors, Signal Transduction, Muscle, Skeletal, Sarcopenia
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
