Unraveling the Complexities of SIRT1-Mediated Mitochondrial Regulation in Skeletal Muscle
Open accessAbstract
In Brief Sirtuin 1 (SIRT1) is a purported central regulator of skeletal muscle mitochondrial biogenesis. Herein, we discuss our recent work using conditional mouse models, which highlight the complexities of SIRT1 biology in vivo, and question the role of SIRT1 in regulating mitochondrial function and mitochondrial adaptations to endurance exercise. Furthermore, we discuss the possible contribution of proposed SIRT1 substrates to muscle mitochondrial biogenesis. Endurance exercise–induced increases in skeletal muscle mitochondrial content are proposed to work through SIRT1 and its downstream substrates.
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?
SIRT1 is activated by metabolic stress and, through its relationship with lactate/NAD+, is activated in an intensity-dependent manner.
“Like AMPK, SIRT1 is activated by metabolic stress and as a result of its relationship with lactate/NAD+, is activated in an intensity-dependent manner [56].”
From Using Molecular Biology to Maximize Concurrent Training (2014) · cites this paper as [56]
The “SIRT1 signaling in skeletal muscle” section describes SIRT1 as a metabolic sensor sensitive to changes in lactate and NAD+. The “SIRT1 and AMPK” section also reports SIRT1 activation following a rise in NAD+. Neither passage establishes that SIRT1 activation varies with exercise intensity, so the intensity-dependent part is unsupported. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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
AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
Cantó, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M., Noriega, L., Milne, J. C., Elliott, P. J., Puigserver, P., & Auwerx, J. (2009) · Nature · doi:10.1038/nature07813 · Cited by 3,300 · see citing works
Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1
Rodgers, J. T., Lerin, C., Haas, W., Gygi, S. P., Spiegelman, B. M., & Puigserver, P. (2005) · Nature · doi:10.1038/nature03354 · Cited by 3,160 · see citing works
hSIR2SIRT1 Functions as an NAD-Dependent p53 Deacetylase
Vaziri, H., Dessain, S. K., Eaton, E. N., Imai, S., Frye, R. A., Pandita, T. K., Guarente, L., & Weinberg, R. A. (2001) · Cell · doi:10.1016/s0092-8674(01)00527-x · Cited by 2,653 · see citing works
Mammalian Sirtuins: Biological Insights and Disease Relevance
Haigis, M. C., & Sinclair, D. A. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092250 · Cited by 2,085 · see citing works
PGC-1α, SIRT1 and AMPK, an energy sensing network that controls energy expenditure
Cantó, C., & Auwerx, J. (2009) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328328d0a4 · Cited by 1,624 · see citing works
Price, N. L., Gomes, A. P., Ling, A. J. Y., Duarte, F. V., Martin-Montalvo, A., North, B. J., Agarwal, B., Ye, L., Ramadori, G., Teodoro, J. S., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.003 · Cited by 1,602 · see citing works
Biochemical Adaptations in Muscle
Holloszy, J. O. (1967) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)96046-1 · Cited by 1,517 · see citing works
Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC‐1α
Gerhart‐Hines, Z., Rodgers, J. T., Bare, O., Lerin, C., Kim, S., Mostoslavsky, R., Alt, F. W., Wu, Z., & Puigserver, P. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601633 · Cited by 1,294 · see citing works
Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice
Cheng, H.-L., Mostoslavsky, R., Saito, S., Manis, J. P., Gu, Y., Patel, P., Bronson, R., Appella, E., Alt, F. W., & Chua, K. F. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1934713100 · Cited by 1,095 · 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
SIRT1 Modulation of the Acetylation Status, Cytosolic Localization, and Activity of LKB1
Lan, F., Cacicedo, J. M., Ruderman, N., & Ido, Y. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805711200 · Cited by 825 · see citing works
Fulco, M., Cen, Y., Zhao, P., Hoffman, E. P., McBurney, M. W., Sauve, A. A., & Sartorelli, V. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.02.004 · Cited by 821 · see citing works
Sirtuin 1 and Sirtuin 3: Physiological Modulators of Metabolism
Nogueiras, R., Habegger, K. M., Chaudhary, N., Finan, B., Banks, A. S., Dietrich, M. O., Horváth, T. L., Sinclair, D. A., Pfluger, P. T., & Tschöp, M. H. (2012) · Physiological Reviews · doi:10.1152/physrev.00022.2011 · Cited by 712 · see citing works
Lundby, A., Lage, K., Weinert, B. T., Bekker‐Jensen, D. B., Secher, A., Skovgaard, T., Kelstrup, C. D., Dmytriyev, A., Choudhary, C., Lundby, C., et al. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.07.006 · Cited by 544 · see citing works
SirT1 Regulates Energy Metabolism and Response to Caloric Restriction in Mice
Boily, G., Seifert, E. L., Bevilacqua, L., He, X. H., Sabourin, G., Estey, C., Moffat, C., Crawford, S., Saliba, S., Jardine, K., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001759 · Cited by 444 · see citing works
Lerin, C., Rodgers, J. T., Kalume, D. E., Kim, S.-H., Pandey, A., & Puigserver, P. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.04.013 · Cited by 443 · see citing works
Histone deacetylase degradation andMEF2 activation promote the formation of slow-twitch myofibers
Potthoff, M. J., Wu, H., Arnold, M., Shelton, J. M., Backs, J., McAnally, J., Richardson, J. A., Bassel‐Duby, R., & Olson, E. N. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31960 · Cited by 416 · see citing works
Cui, L., Supinski, A., Savas, J. N., Yates, J. R., Bordone, L., Guarente, L., Cohen, D. E., Mazzulli, J. R., Krainc, D., & Jeong, H. (2011) · PubMed Central · doi:10.1038/nm.2559 · Cited by 367 · see citing works
Bouras, T., Fu, M., Sauve, A. A., Wang, F., Quong, A. A., Perkins, N. D., Hay, R. T., Gu, W. J., & Pestell, R. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m408748200 · Cited by 354 · see citing works
Regulation of MEF2 by Histone Deacetylase 4- and SIRT1 Deacetylase-Mediated Lysine Modifications
Zhao, X., Sternsdorf, T., Bolger, T. A., Evans, R. M., & Yao, T.-P. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.19.8456-8464.2005 · Cited by 264 · see citing works
NCoR1 Is a Conserved Physiological Modulator of Muscle Mass and Oxidative Function
Yamamoto, H., Williams, E. G., Mouchiroud, L., Cantó, C., Fan, W., Downes, M., Héligon, C., Barish, G. D., Desvergne, B., Evans, R. M., et al. (2011) · Cell · doi:10.1016/j.cell.2011.10.017 · Cited by 261 · see citing works
A role for the transcriptional coactivator PGC-1α in muscle refueling.
Wende, A. R., Schaeffer, P. J., Parker, G. J., Zechner, C., Han, D.-H., Chen, M. M., Hancock, C. R., Lehman, J. J., Huss, J. M., McClain, D. A., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m707006200 · Cited by 257 · see citing works
Amat, R., Planavila, A., Chen, S. L., Iglesias, R., Giralt, M., & Villarroya, F. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.022749 · Cited by 218 · see citing works
Sirt1 enhances skeletal muscle insulin sensitivity in mice during caloric restriction
Schenk, S., McCurdy, C. E., Philp, A., Chen, M. Z., Holliday, M. J., Bandyopadhyay, G. K., Osborn, O., Baar, K., & Olefsky, J. M. (2011) · Journal of Clinical Investigation · doi:10.1172/jci58554 · Cited by 197 · see citing works
Self-citationNAD+/NADH and skeletal muscle mitochondrial adaptations to exercise
White, A. T., & Schenk, S. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00054.2012 · Cited by 193 · see citing works
Self-citationResveratrol as a calorie restriction mimetic: therapeutic implications
Chung, J. H., Manganiello, V., & Dyck, J. R. B. (2012) · Trends in Cell Biology · doi:10.1016/j.tcb.2012.07.004 · Cited by 192 · see citing works
Philp, A., Chen, A., Lan, D., Meyer, G. A., Murphy, A. N., Knapp, A. E., Olfert, I. M., McCurdy, C. E., Marcotte, G. R., Hogan, M. C., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.261685 · Cited by 184 · see citing works
Self-citationAMP-activated protein kinase phosphorylates transcription factors of the CREB family
Thomson, D. M., Herway, S. T., Fillmore, N., Kim, H., Brown, J. D., Barrow, J. R., & Winder, W. W. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00900.2007 · Cited by 183 · see citing works
Role of p53 in mitochondrial biogenesis and apoptosis in skeletal muscle
Saleem, A., Adhihetty, P. J., & Hood, D. A. (2008) · Physiological Genomics · doi:10.1152/physiolgenomics.90346.2008 · Cited by 182 · see citing works
CREB and ChREBP oppositely regulate SIRT1 expression in response to energy availability
Noriega, L. G., Feige, J. N., Cantó, C., Yamamoto, H., Yu, J., Herman, M. A., Mataki, C., Kahn, B. B., & Auwerx, J. H. (2011) · EMBO Reports · doi:10.1038/embor.2011.151 · Cited by 172 · see citing works
Qiang, L., Lin, H. V., Kim-Muller, J. Y., Welch, C. L., Gu, W. J., & Accili, D. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.10.007 · Cited by 129 · see citing works
Akimoto, T., Sorg, B. S., & Yan, Z. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00425.2003 · Cited by 117 · see citing works
Gurd, B. J., Yoshida, Y., Lally, J., Holloway, G. P., & Bonen, A. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2008.168096 · Cited by 91 · see citing works
A perspective on the determination of mitochondrial biogenesis
Miller, B. F., & Hamilton, K. L. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00578.2011 · Cited by 86 · see citing works
SirT1 fails to affect p53‐mediated biological functions
Kamel, C., Abrol, M., Jardine, K. E., He, X., & McBurney, M. W. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00191.x · Cited by 64 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Fyfe, J. J., Bishop, D. J., & Stepto, N. K. (2014) · Sports Medicine · doi:10.1007/s40279-014-0162-1 · Cited by 347 · see citing works
Egan, B., & Sharples, A. P. (2023) · Physiological Reviews · doi:10.1152/physrev.00054.2021 · Cited by 278 · see citing works
Tuning fatty acid oxidation in skeletal muscle with dietary fat and exercise
Fritzen, A. M., Lundsgaard, A.-M., & Kiens, B. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0405-1 · Cited by 180 · see citing works
Using Molecular Biology to Maximize Concurrent Training
Baar, K. (2014) · Sports Medicine · doi:10.1007/s40279-014-0252-0 · Cited by 118 · see citing works
“Like AMPK, SIRT1 is activated by metabolic stress and as a result of its relationship with lactate/NAD, is activated in an intensity-dependent manner [56].”
Background
- Authors
- Philp, A., & Schenk, S.
- Affiliations
- University of Birmingham (GB)
- University of California San Diego (US)
- Corresponding author
- Schenk, Simon
- Venue
- Exercise and Sport Sciences Reviews
- Published
- 2013-07
- Volume
- 41
- Issue
- 3
- Pages
- 174-181
- ISSN
- 0091-6331 (ISSN-L)
- PMC
- PMC3707796
- OpenAlex
- W1980290138
- Cited by
- 39
- References
- 35
- Citations by year
- 2024: 2 · 2023: 2 · 2022: 6 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 6 · 2016: 3 · 2015: 1 · 2014: 6 · 2013: 1
- FWCI
- 0.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Exercise and Sport Sciences Reviews (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R01AG043120)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR061303, P30AR058878)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R24HD050837)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- SIRT1, sirtuins, skeletal muscle, mitochondrial biogenesis, mitochondrial function, endurance exercise, exercise adaptation, conditional mouse model
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Oxidation-Reduction, Physical Conditioning, Animal, Transcription Factors, Signal Transduction, Tumor Suppressor Protein p53, Cyclic AMP Response Element-Binding Protein, Muscle, Skeletal, AMP-Activated Protein Kinases, Sirtuin 1, Mitochondrial Turnover, MEF2 Transcription Factors
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
