Caloric restriction and exercise “mimetics”: ready for prime time

Handschin, Christoph

doi:10.1016/j.phrs.2015.11.009

Cited by 72Sirtuins and Resveratrol in MedicineAdipose Tissue and MetabolismMetabolism, Diabetes, and Cancer

Caloric restriction and exercise “mimetics”: ready for prime time

Open access

Handschin, Christoph·2016·Pharmacological Research

DOI 10.1016/j.phrs.2015.11.009PMC PMC4970791

Open this paper in CoChat — free account

Abstract

Exercise and diet are powerful interventions to prevent and ameliorate various pathologies. The development of pharmacological agents that confer exercise- or caloric restriction-like phenotypic effects is thus an appealing therapeutic strategy in diseases or even when used as life-style and longevity drugs. Such so-called exercise or caloric restriction "mimetics" have so far mostly been described in pre-clinical, experimental settings with limited translation into humans. Interestingly, many of these compounds activate related signaling pathways, most often postulated to act on the common downstream effector peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in skeletal muscle. In this review, resveratrol and other exercise- and caloric restriction "mimetics" are discussed with a special focus on feasibility, chances and limitations of using such compounds in patients as well as in healthy individuals.

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

Crossref · 10.1016/j.phrs.2015.11.009

Cites

105 of 105 references verified0 citation errors · 0 not checkable

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?

Most pharmaceutical therapeutics target major players or key nodes in metabolic circuits, many acting on mitochondrial function.
“Most pharmaceutical therapeutics target major players or key nodes in metabolic circuits, many acting on mitochondrial function (245).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [245]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
(2002) · New England Journal of Medicine · doi:10.1056/nejmoa012512 · Cited by 19,011 · cited 1× · see citing works
“In contrast, lifestyle-based interventions combining exercise and diet have an enormous potential to prevent and treat numerous chronic pathologies, in some cases even rivaling or surpassing the efficacy of drugs [9,10].”
Background
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652 · see citing works
A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis
Boström, P., Wu, J., Jedrychowski, M. P., Korde, A., Ye, L., Lo, J. C., Rasbach, K. A., Boström, E. A., Choi, J. H., Long, J. Z., et al. (2012) · Nature · doi:10.1038/nature10777 · Cited by 4,810 · see citing works
Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1α
Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.11.013 · Cited by 4,057 · see citing works
Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., Zipkin, R. E., Chung, P., Kisielewski, A., Zhang, L.-L., et al. (2003) · Nature · doi:10.1038/nature01960 · Cited by 3,796 · see citing works
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
Extending Healthy Life Span—From Yeast to Humans
Fontana, L., Partridge, L., & Longo, V. D. (2010) · Science · doi:10.1126/science.1172539 · Cited by 3,023 · see citing works
A Potential Decline in Life Expectancy in the United States in the 21st Century
Olshansky, S. J., Passaro, D. J., Hershow, R. C., Layden, J., Carnes, B. A., Brody, J., Hayflick, L., Butler, R. N., Allison, D. B., & Ludwig, D. S. (2005) · New England Journal of Medicine · doi:10.1056/nejmsr043743 · Cited by 2,612 · see citing works
Lack of Exercise Is a Major Cause of Chronic Diseases
Booth, F. W., Roberts, C. K., & Laye, M. J. (2012) · Comprehensive Physiology · doi:10.1002/cphy.c110025 · Cited by 2,575 · see citing works
Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres
Lin, J., Wu, H., Tarr, P. T., Zhang, C.-Y., Wu, Z., Boss, O., Michael, L. F., Puigserver, P., Isotani, E., Olson, E. N., et al. (2002) · Nature · doi:10.1038/nature00904 · Cited by 2,546 · see citing works
AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α
Jäger, S., Handschin, C., St.-Pierre, J., & Spiegelman, B. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705070104 · Cited by 2,491 · see citing works
Self-citation
Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys
Colman, R. J., Anderson, R. M., Johnson, S. C., Kastman, E. K., Kosmatka, K. J., Beasley, T. M., Allison, D. B., Cruzen, C., Simmons, H. A., Kemnitz, J. W., et al. (2009) · Science · doi:10.1126/science.1173635 · Cited by 2,277 · see citing works
A Potential Decline in Life Expectancy in the United States in the 21st Century
Olshansky, S. J., Passaro, D. J., Hershow, R. C., Layden, J. E., Carnes, B. A., Brody, J. A., Hayflick, L., Butler, R. N., Allison, D. B., & Ludwig, D. S. (2005) · Obstetrical & Gynecological Survey · doi:10.1097/01.ogx.0000167407.83915.e7 · Cited by 1,944 · see citing works
Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
Yoon, J. C., Puigserver, P., Chen, G., Donovan, J., Wu, Z., Rhee, J., Adelmant, G., Stafford, J., Kahn, C. R., Granner, D. K., et al. (2001) · Nature · doi:10.1038/35093050 · Cited by 1,821 · see citing works
Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes
Milne, J. C., Lambert, P. D., Schenk, S., Carney, D. P., Smith, J. J., Gagne, D. J., Jin, L., Boss, O., Perni, R. B., Vu, C. B., et al. (2007) · Nature · doi:10.1038/nature06261 · Cited by 1,707 · see citing works
Antioxidants prevent health-promoting effects of physical exercise in humans
Ristow, M., Zarse, K., Oberbach, A., Klöting, N., Birringer, M., Kiehntopf, M., Stumvoll, M., Kahn, C. R., & Blüher, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903485106 · Cited by 1,582 · see citing works
Metformin improves healthspan and lifespan in mice
Martin-Montalvo, A., Mercken, E. M., Mitchell, S. J., Palacios, H. H., Mote, P. L., Scheibye-Knudsen, M., Gomes, A. P., Ward, T. M., Minor, R. K., Blouin, M.-J., et al. (2013) · Nature Communications · doi:10.1038/ncomms3192 · Cited by 1,445 · 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
Child and adolescent obesity: part of a bigger picture
Lobstein, T., Jackson-Leach, R., Moodie, M. L., Hall, K. D., Gortmaker, S. L., Swinburn, B. A., James, W. P. T., Wang, Y., & McPherson, K. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61746-3 · Cited by 1,279 · see citing works
AMPK and PPARδ Agonists Are Exercise Mimetics
Narkar, V. A., Downes, M., Yu, R. T., Embler, E., Wang, Y.-X., Banayo, E., Mihaylova, M. M., Nelson, M. C., Zou, Y., Juguilon, H., et al. (2008) · Cell · doi:10.1016/j.cell.2008.06.051 · Cited by 1,222 · see citing works
Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span
Pearson, K. J., Baur, J. A., Lewis, K. N., Peshkin, L., Price, N. L., Labinskyy, N., Swindell, W. R., Kamara, D., Minor, R. K., Perez, E., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.06.011 · Cited by 1,162 · see citing works
Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study
Mattison, J. A., Roth, G. S., Beasley, T. M., Tilmont, E. M., Handy, A. M., Herbert, R. L., Longo, D. L., Allison, D. B., Young, J. E., Bryant, M., et al. (2012) · Nature · doi:10.1038/nature11432 · Cited by 1,145 · see citing works
Muscle wasting in disease: molecular mechanisms and promising therapies
Cohen, S., Nathan, J. A., & Goldberg, A. L. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4467 · Cited by 1,089 · 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
Self-citation
Making new contacts: the mTOR network in metabolism and signalling crosstalk
Shimobayashi, M., & Hall, M. N. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3757 · Cited by 1,053 · see citing works
Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β
Cho, H., Zhao, X., Hatori, M., Yu, R. T., Barish, G. D., Lam, M. T., Chong, L.-W., DiTacchio, L., Atkins, A. R., Glass, C. K., et al. (2012) · Nature · doi:10.1038/nature11048 · Cited by 1,037 · see citing works
Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis
Rao, R. R., Long, J. Z., White, J. P., Svensson, K. J., Lou, J., Lokurkar, I., Jedrychowski, M. P., Ruas, J. L., Wrann, C. D., Lo, J. C., et al. (2014) · Cell · doi:10.1016/j.cell.2014.03.065 · Cited by 973 · see citing works
Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges
Chaix, A., Zarrinpar, A., Miu, P., & Panda, S. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.11.001 · Cited by 956 · see citing works
Reversal of Cancer Cachexia and Muscle Wasting by ActRIIB Antagonism Leads to Prolonged Survival
Zhou, X., Wang, J. L., Lu, J., Song, Y., Kwak, K. S., Jiao, Q., Rosenfeld, R., Chen, Q., Boone, T. C., Simonet, W. S., et al. (2010) · Cell · doi:10.1016/j.cell.2010.07.011 · Cited by 941 · see citing works
SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1
Pacholec, M., Bleasdale, J. E., Chrunyk, B., Cunningham, D., Flynn, D., Garofalo, R. S., Griffith, D., Griffor, M., Loulakis, P., Pabst, B., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.088682 · Cited by 915 · see citing works
Rapamycin, But Not Resveratrol or Simvastatin, Extends Life Span of Genetically Heterogeneous Mice
Miller, R. A., Harrison, D. E., Astle, C. M., Baur, J. A., Boyd, A. R., de Cabo, R., Fernandez, E., Flurkey, K., Javors, M. A., Nelson, J. F., et al. (2011) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glq178 · Cited by 896 · see citing works
Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists
Solt, L. A., Wang, Y., Banerjee, S., Hughes, T., Kojetin, D. J., Lundåsen, T., Shin, Y., Liu, J., Cameron, M. D., Noël, R., et al. (2012) · Nature · doi:10.1038/nature11030 · Cited by 835 · see citing works
Specific SIRT1 Activation Mimics Low Energy Levels and Protects against Diet-Induced Metabolic Disorders by Enhancing Fat Oxidation
Feige, J. N., Lagouge, M., Canto, C., Strehle, A., Houten, S. M., Milne, J. C., Lambert, P. D., Mataki, C., Elliott, P. J., & Auwerx, J. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.08.017 · Cited by 719 · see citing works
The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance
Lee, C., Zeng, J., Drew, B. G., Sallam, T., Martin-Montalvo, A., Wan, J., Kim, S.-J., Mehta, H., Hevener, A. L., de Cabo, R., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.02.009 · Cited by 715 · see citing works
Aging, frailty and age-related diseases
Fülöp, T., Larbi, A., Witkowski, J. M., McElhaney, J. E., Loeb, M. B., Mitnitski, A., & Pawelec, G. (2010) · Biogerontology · doi:10.1007/s10522-010-9287-2 · Cited by 655 · see citing works
β-Aminoisobutyric Acid Induces Browning of White Fat and Hepatic β-Oxidation and Is Inversely Correlated with Cardiometabolic Risk Factors
Roberts, L. D., Boström, P., O’Sullivan, J. F., Schinzel, R. T., Lewis, G. D., Dejam, A., Lee, Y.-K., Palma, M. J., Calhoun, S., Georgiadi, A., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.12.003 · Cited by 643 · see citing works
Transcriptional coactivator PGC-1α integrates the mammalian clock and energy metabolism
Liu, C., Li, S., Liu, T., Borjigin, J., & Lin, J. D. (2007) · Nature · doi:10.1038/nature05767 · Cited by 643 · see citing works
Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1α muscle-specific knock-out animals.
Handschin, C., Chin, S., Li, P., Liu, F., Maratos-Flier, E., LeBrasseur, N. K., Yan, Z., & Spiegelman, B. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704817200 · Cited by 611 · see citing works
Self-citation
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
Compliance in heart failure patients: the importance of knowledge and beliefs
van der Wal, M. H. L., Jaarsma, T., Moser, D. K., Veeger, N. J. G. M., van Gilst, W. H., & van Veldhuisen, D. J. (2005) · European Heart Journal · doi:10.1093/eurheartj/ehi603 · Cited by 535 · see citing works
2,4-Dinitrophenol (DNP): A Weight Loss Agent with Significant Acute Toxicity and Risk of Death
Grundlingh, J., Dargan, P. I., El-Zanfaly, M., & Wood, D. M. (2011) · Journal of Medical Toxicology · doi:10.1007/s13181-011-0162-6 · Cited by 470 · see citing works
Waging war on physical inactivity: using modern molecular ammunition against an ancient enemy.
Booth, F., Chakravarthy, M., Gordon, S., & Spangenburg, E. (2002) · Journal of applied physiology · doi:10.1152/japplphysiol.00073.2002 · Cited by 467 · see citing works
Rev-erb-α modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy
Woldt, E., Sebti, Y., Solt, L. A., Duhem, C., Lancel, S., Eeckhoute, J., Hesselink, M. K. C., Paquet, C., Delhaye, S., Shin, Y., et al. (2013) · Nature Medicine · doi:10.1038/nm.3213 · Cited by 454 · see citing works
Celastrols as Inducers of the Heat Shock Response and Cytoprotection
Westerheide, S. D., Bosman, J. D., Mbadugha, B. N. A., Kawahara, T. L. A., Matsumoto, G., Kim, S., Gu, W., Devlin, J. P., Silverman, R. B., & Morimoto, R. I. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409267200 · Cited by 427 · see citing works
The starvation hormone, fibroblast growth factor-21, extends lifespan in mice
Zhang, Y., Xie, Y., Berglund, E. D., Coate, K. C., He, T. T., Katafuchi, T., Xiao, G., Potthoff, M. J., Wei, W., Wan, Y., et al. (2012) · eLife · doi:10.7554/elife.00065 · Cited by 420 · see citing works
Skeletal muscle as an endocrine organ: PGC-1α, myokines and exercise
Schnyder, S., & Handschin, C. (2015) · Bone · doi:10.1016/j.bone.2015.02.008 · Cited by 419 · see citing works
Self-citation
Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete's paradox revisited
Dubé, J. J., Amati, F., Stefanovic-Racic, M., Toledo, F. G. S., Sauers, S. E., & Goodpaster, B. H. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00769.2007 · Cited by 378 · see citing works
Muscle-specific expression of PPARγ coactivator-1α improves exercise performance and increases peak oxygen uptake
Calvo, J. A., Daniels, T. G., Wang, X., Paul, A., Lin, J., Spiegelman, B. M., Stevenson, S. C., & Rangwala, S. M. (2008) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01231.2007 · Cited by 377 · see citing works
The Peroxisome Proliferator-Activated Receptor β/δ Agonist, GW501516, Regulates the Expression of Genes Involved in Lipid Catabolism and Energy Uncoupling in Skeletal Muscle Cells
Dressel, U., Allen, T. L., Pippal, J. B., Rohde, P. R., Lau, P., & Muscat, G. E. O. (2003) · Molecular Endocrinology · doi:10.1210/me.2003-0151 · Cited by 370 · see citing works
PGC1α expression is controlled in skeletal muscles by PPARβ, whose ablation results in fiber-type switching, obesity, and type 2 diabetes
Schuler, M. J., Ali, F., Chambon, C., Duteil, D., Bornert, J., Tardivel, A., Desvergne, B., Wahli, W., Chambon, P., & METZGER, D. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.10.003 · Cited by 368 · see citing works
mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass
Kunkel, S. D., Suneja, M., Ebert, S. M., Bongers, K. S., Fox, D. K., Malmberg, S. E., Alipour, F., Shields, R. K., & Adams, C. M. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.03.020 · Cited by 345 · cited 2× · see citing works
“Ursolic acid was identified in a screen comparing the gene expression pattern of different human settings of muscle atrophy with those of the Connectivity map, a collection of global gene expression data of various compounds in different cell types [74].”
Background
Celastrol Protects against Obesity and Metabolic Dysfunction through Activation of a HSF1-PGC1α Transcriptional Axis
Ma, X., Xu, L., Alberobello, A. T., Gavrilova, O., Bagattin, A., Skarulis, M. C., Liu, J., Finkel, T., & Mueller, E. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.08.005 · Cited by 337 · see citing works
Abnormal glucose homeostasis in skeletal muscle–specific PGC-1α knockout mice reveals skeletal muscle–pancreatic β cell crosstalk
Handschin, C., Choi, C. S., Chin, S., Kim, S., Kawamori, D., Kurpad, A. J., Neubauer, N., Hu, J., Mootha, V. K., Kim, Y.-B., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31785 · Cited by 335 · see citing works
Self-citation
The cAMP/PKA Pathway Rapidly Activates SIRT1 to Promote Fatty Acid Oxidation Independently of Changes in NAD+
Gerhart‐Hines, Z., Dominy, J. E., Blättler, S. M., Jedrychowski, M. P., Banks, A. S., Lim, J.-H., Chim, H., Gygi, S. P., & Puigserver, P. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.12.005 · Cited by 323 · see citing works
Of mice and men: the benefits of caloric restriction, exercise, and mimetics
Mercken, E. M., Carboneau, B. A., Krzysik-Walker, S. M., & de Cabo, R. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2011.11.005 · Cited by 318 · see citing works
Myostatin/activin pathway antagonism: molecular basis and therapeutic potential
Han, H. Q., Zhou, X., Mitch, W. E., & Goldberg, A. L. (2013) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2013.05.019 · Cited by 314 · see citing works
The pharmacology of resveratrol in animals and humans
Park, E.-J., & Pezzuto, J. M. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.01.014 · Cited by 302 · see citing works
Intermittent fasting vs daily calorie restriction for type 2 diabetes prevention: a review of human findings
Barnosky, A., Hoddy, K. K., Unterman, T. G., & Varady, K. A. (2014) · Translational research · doi:10.1016/j.trsl.2014.05.013 · Cited by 294 · see citing works
Prevalence of Doping Use in Elite Sports: A Review of Numbers and Methods
de Hon, O. M., Kuipers, H., & van Bottenburg, M. (2014) · Sports Medicine · doi:10.1007/s40279-014-0247-x · Cited by 279 · see citing works
Paradoxical effects of increased expression of PGC-1α on muscle mitochondrial function and insulin-stimulated muscle glucose metabolism
Choi, C. S., Befroy, D. E., Codella, R., Kim, S., Reznick, R. M., Hwang, Y.-J., Liu, Z.-X., Lee, H.-Y., Distefano, A., Samuel, V. T., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810339105 · Cited by 279 · see citing works
Self-citation
Resveratrol supplementation: Where are we now and where should we go?
Novelle, M. G., Wahl, D., Diéguez, C., Bernier, M., & de Cabo, R. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.01.002 · Cited by 247 · see citing works
Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men
Gliemann, L., Schmidt, J. F., Olesen, J., Biensø, R. S., Peronard, S. L., Grandjean, S. U., Mortensen, S. P., Nyberg, M., Bangsbo, J., Pilegaard, H., et al. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2013.258061 · Cited by 244 · see citing works
Ten Years of Life: Is It a Matter of Choice?
Fraser, G. E., & Shavlik, D. J. (2001) · Archives of Internal Medicine · doi:10.1001/archinte.161.13.1645 · Cited by 237 · see citing works
Effects of Resveratrol and SIRT1 on PGC-1α Activity and Mitochondrial Biogenesis: A Reevaluation
Higashida, K., Kim, S. H., Jung, S. R., Asaka, M., Holloszy, J. O., & Han, D.-H. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001603 · Cited by 228 · see citing works
Lifetime sedentary living accelerates some aspects of secondary aging
Booth, F. W., Laye, M. J., & Roberts, M. D. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00420.2011 · Cited by 207 · see citing works
(–)-Epicatechin enhances fatigue resistance and oxidative capacity in mouse muscle
Nogueira, L., Ramirez‐Sanchez, I., Perkins, G. A., Murphy, A., Taub, P. R., Ceballos, G., Villarreal, F. J., Hogan, M. C., & Malek, M. H. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2011.209924 · Cited by 205 · see citing works
Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease
Rodino‐Klapac, L. R., Haidet, A. M., Kota, J., Handy, C., Kaspar, B. K., & Mendell, J. R. (2009) · Muscle & Nerve · doi:10.1002/mus.21244 · Cited by 194 · see citing works
NAD <sup>+</sup> metabolism: A therapeutic target for age-related metabolic disease
Mouchiroud, L., Houtkooper, R. H., & Auwerx, J. (2013) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.789479 · Cited by 193 · see citing works
Estrogen-related Receptor γ Is a Key Regulator of Muscle Mitochondrial Activity and Oxidative Capacity
Rangwala, S. M., Wang, X., Calvo, J. A., Lindsley, L., Zhang, Y., Deyneko, G., Beaulieu, V., Gao, J., Turner, G. M., & Markovits, J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.125401 · Cited by 192 · see citing works
Exercise and PGC-1α-Independent Synchronization of Type I Muscle Metabolism and Vasculature by ERRγ
Narkar, V. A., Fan, W., Downes, M., Yu, R. T., Jonker, J. W., Alaynick, W. A., Banayo, E., Karunasiri, M. S., Lorca, S., & Evans, R. M. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.01.019 · Cited by 185 · see citing works
Caloric restriction and the aging process: a critique
Sohal, R. S., & Forster, M. J. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.05.015 · Cited by 178 · see citing works
Calorie restriction mimetics: Can you have your cake and eat it, too?
Ingram, D. K., & Roth, G. S. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.11.005 · Cited by 162 · see citing works
Nitric oxide regulates mitochondrial oxidative stress protection via the transcriptional coactivator PGC‐1α
Borniquel, S., Valle, I., Cadenas, S., Lamas, S., & Monsalve, M. (2006) · The FASEB Journal · doi:10.1096/fj.05-5189fje · Cited by 147 · see citing works
Expanding roles for AMPK in skeletal muscle plasticity
Mounier, R., Théret, M., Lantier, L., Foretz, M., & Viollet, B. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.02.009 · Cited by 130 · see citing works
Exercise Intolerance in Chronic Heart Failure
Okita, K., Kinugawa, S., & Tsutsui, H. (2013) · Circulation Journal · doi:10.1253/circj.cj-12-1235 · Cited by 124 · see citing works
Molecular Mechanisms of Muscle Plasticity with Exercise
Hoppeler, H. H., Baum, O., Lurman, G. J., & Mueller, M. (2011) · Comprehensive physiology · doi:10.1002/cphy.c100042 · Cited by 120 · see citing works
Exercise training, but not resveratrol, improves metabolic and inflammatory status in skeletal muscle of aged men
Olesen, J., Gliemann, L., Biensø, R., Schmidt, J., Hellsten, Y., & Pilegaard, H. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2013.270256 · Cited by 119 · see citing works
Caloric restriction and its mimetics
Lee, S.-H., & Min, K.-J. (2013) · BMB Reports · doi:10.5483/bmbrep.2013.46.4.033 · Cited by 119 · see citing works
Peroxisome Proliferator-activated Receptor γ Coactivator 1α (PGC-1α) Promotes Skeletal Muscle Lipid Refueling in Vivo by Activating de Novo Lipogenesis and the Pentose Phosphate Pathway*
Summermatter, S., Baum, O., Santos, G., Hoppeler, H. H., & Handschin, C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.145995 · Cited by 114 · see citing works
Self-citation
FGF21 Revolutions: Recent Advances Illuminating FGF21 Biology and Medicinal Properties
Kharitonenkov, A., & DiMarchi, R. D. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.09.007 · Cited by 114 · see citing works
Drug treatment of obesity: Current status and future prospects
Kakkar, A. K., & Dahiya, N. (2015) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2015.01.005 · Cited by 113 · see citing works
Metabolic effects of resveratrol: Addressing the controversies
Bitterman, J. L., & Chung, J. H. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1808-8 · Cited by 109 · see citing works
The biology of PGC-1α and its therapeutic potential
Handschin, C. (2009) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.03.006 · Cited by 108 · see citing works
Self-citation
Exercise: it's the real thing!
Hawley, J. A., & Holloszy, J. O. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.2009.00185.x · Cited by 108 · see citing works
Yin Yang 1 Deficiency in Skeletal Muscle Protects against Rapamycin-Induced Diabetic-like Symptoms through Activation of Insulin/IGF Signaling
Blättler, S. M., Cunningham, J. T., Verdeguer, F., Chim, H., Haas, W., Liu, H., Romanino, K., Rüegg, M. A., Gygi, S. P., Shi, Y., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.03.008 · Cited by 105 · see citing works
Lack of adequate appreciation of physical exercise's complexities can pre‐empt appropriate design and interpretation in scientific discovery
Booth, F. W., & Laye, M. J. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2009.179507 · Cited by 99 · see citing works
PGC-1α Improves Glucose Homeostasis in Skeletal Muscle in an Activity-Dependent Manner
Summermatter, S., Shui, G., Maag, D., Santos, G., Wenk, M. R., & Handschin, C. (2012) · Diabetes · doi:10.2337/db12-0291 · Cited by 96 · see citing works
Self-citation
Resveratrol and cardiovascular health – Promising therapeutic or hopeless illusion?
Tang, P. C., Ng, Y.-F., Ho, S., Gyda, M., & Chan, S. (2014) · Pharmacological Research · doi:10.1016/j.phrs.2014.08.001 · Cited by 87 · see citing works
Integrative and Systemic Approaches for Evaluating PPARβ/δ (PPARD) Function
Attianese, G. M. P. G., & Desvergne, B. (2015) · Nuclear Receptor Signaling · doi:10.1621/nrs.13001 · Cited by 84 · see citing works
Resveratrol supplementation does not augment performance adaptations or fibre-type-specific responses to high-intensity interval training in humans
Scribbans, T. D., Ma, J. K., Edgett, B. A., Vorobej, K. A., Mitchell, A. S., Zelt, J. G. E., Simpson, C. A., Quadrilatero, J., & Gurd, B. J. (2014) · Applied Physiology Nutrition and Metabolism · doi:10.1139/apnm-2014-0070 · Cited by 79 · see citing works
Irisin, a unique non-inflammatory myokine in stimulating skeletal muscle metabolism
Vaughan, R. A., Gannon, N. P., Mermier, C. M., & Conn, C. A. (2015) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-015-0433-9 · Cited by 77 · see citing works
Complex Coordination of Cell Plasticity by a PGC-1α-controlled Transcriptional Network in Skeletal Muscle
Kupr, B., & Handschin, C. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00325 · Cited by 68 · see citing works
Self-citation
Disorder-to-order transition underlies the structural basis for the assembly of a transcriptionally active PGC-1α/ERRγ complex
Devarakonda, S., Gupta, K., Chalmers, M. J., Hunt, J. F., Griffin, P. R., Duyne, G. D. V., & Spiegelman, B. M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113813108 · Cited by 68 · see citing works
Anti-ageing pill pushed as bona fide drug
Hayden, E. C. (2015) · Nature · doi:10.1038/522265a · Cited by 58 · see citing works
Exercise Pills: At the Starting Line
Li, S., & Laher, I. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.08.014 · Cited by 54 · see citing works
Utilizing small nutrient compounds as enhancers of exercise-induced mitochondrial biogenesis
Craig, D. M., Ashcroft, S. P., Belew, M. Y., Stocks, B., Currell, K., Baar, K., & Philp, A. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00296 · Cited by 45 · see citing works
PGC-1α and exercise in the control of body weight
Summermatter, S., & Handschin, C. (2012) · International Journal of Obesity · doi:10.1038/ijo.2012.12 · Cited by 45 · see citing works
Self-citation
Androgen receptor as a therapeutic target
Gao, W. (2010) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2010.08.002 · Cited by 42 · see citing works
Exercise in a Pill: Feasibility of Energy Expenditure Targets
Himms-Hagen, J. (2004) · Current Drug Target -CNS & Neurological Disorders · doi:10.2174/1568007043337076 · Cited by 39 · cited 1× · see citing works
“The concept of designing pharmacological agents that engage the same or at least similar biological programs as bona fide training was initially focused on facultative energy expenditure [28].”
Background
The fine line between lifespan extension and shortening in response to caloric restriction
Szafranski, K., & Mekhail, K. (2014) · Nucleus · doi:10.4161/nucl.27929 · Cited by 33 · see citing works
The erosion of physical activity in Western societies: an economic death march
Booth, F. W., & Hawley, J. A. (2015) · Diabetologia · doi:10.1007/s00125-015-3617-5 · Cited by 29 · see citing works
Resveratrol and SRT1720 Elicit Differential Effects in Metabolic Organs and Modulate Systemic Parameters Independently of Skeletal Muscle Peroxisome Proliferator-activated Receptor γ Co-activator 1α (PGC-1α)
Svensson, K., Schnyder, S., Albert, V., Cardel, B., Quagliata, L., Terracciano, L., & Handschin, C. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.590653 · Cited by 26 · see citing works
Self-citation
Androgen Receptor Modulators: A Marriage of Chemistry and Biology
McEwan, I. J. (2013) · Future Medicinal Chemistry · doi:10.4155/fmc.13.69 · Cited by 23 · see citing works
Treating the elite athlete: anti-doping information for the health professional.
Tandon, S., Bowers, L. D., & Fedoruk, M. (2015) · PubMed · Cited by 22 · see citing works
The coactivator PGC-1α regulates skeletal muscle oxidative metabolism independently of the nuclear receptor PPARβ/δ in sedentary mice fed a regular chow diet
Pérez‐Schindler, J., Svensson, K., Vargas‐Fernández, E., Santos, G., Wahli, W., & Handschin, C. (2014) · Diabetologia · doi:10.1007/s00125-014-3352-3 · Cited by 18 · see citing works
Self-citation

Flagged first, then by citations

Sorted by citations

Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease
Smith, R. L., Soeters, M. R., Wüst, R. C. I., & Houtkooper, R. H. (2018) · Endocrine Reviews · doi:10.1210/er.2017-00211 · Cited by 787 · see citing works
Mitochondria and ageing: Role in heart, skeletal muscle and adipose tissue
Boengler, K., Kosiol, M., Mayr, M., Schulz, R., & Rohrbach, S. (2017) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12178 · Cited by 421 · see citing works
Metformin Use Associated With Reduced Risk of Dementia in Patients With Diabetes: A Systematic Review and Meta-Analysis
Campbell, J. M., Stephenson, M. D., de Courten, B., Chapman, I., Bellman, S. M., & Aromataris, E. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180263 · Cited by 292 · see citing works
Endocrine Crosstalk Between Skeletal Muscle and the Brain
Delezie, J., & Handschin, C. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00698 · Cited by 270 · see citing works
Self-citation
Acute Sarcopenia Secondary to Hospitalisation - An Emerging Condition Affecting Older Adults
Welch, C., Hassan-Smith, Z. K., Greig, C. A., Lord, J. M., & Jackson, T. (2018) · Aging and Disease · doi:10.14336/ad.2017.0315 · Cited by 223 · see citing works
The molecular athlete: exercise physiology from mechanisms to medals
Furrer, R., Hawley, J. A., & Handschin, C. (2023) · Physiological Reviews · doi:10.1152/physrev.00017.2022 · Cited by 232 · see citing works
Self-citation
Mitochondrial dynamics and transport in Alzheimer's disease
Flannery, P. J., & Trushina, E. V. (2019) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2019.06.009 · Cited by 198 · see citing works
MOTS-c: a novel mitochondrial-derived peptide regulating muscle and fat metabolism
Lee, C., Kim, K. H., & Cohen, P. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.05.015 · Cited by 178 · see citing works
Hormetic Effects of Phytochemicals on Health and Longevity
Martel, J., Ojcius, D. M., Ko, Y., Ke, P., Wu, C.-Y., Peng, H., & Young, J. D. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.04.001 · Cited by 163 · 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
Treadmill exercise decreases amyloid-β burden possibly via activation of SIRT-1 signaling in a mouse model of Alzheimer's disease
Koo, J., Kang, E., Oh, Y.-S., Yang, D.-S., & Cho, J. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2016.11.014 · Cited by 148 · see citing works
The Muscle Stem Cell Niche in Health and Disease
Mashinchian, O., Pisconti, A., Moal, E. L., & Bentzinger, C. F. (2017) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2017.08.003 · Cited by 127 · see citing works
Mitochondrial complex I as a therapeutic target for Alzheimer's disease
Trushina, E. V., Trushin, S., & Hasan, M. F. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.11.003 · Cited by 130 · see citing works
Muscle Wasting Diseases: Novel Targets and Treatments
Furrer, R., & Handschin, C. (2018) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010818-021041 · Cited by 93 · see citing works
Self-citation
Exercise as an Anti-inflammatory Therapy for Cancer Cachexia: A Focus on Interleukin-6 Regulation.
Daou, H. (2019) · American Journal of Physiology. Regulatory Integrative and Comparative Physiology · doi:10.1152/ajpregu.00147.2019 · Cited by 74 · see citing works
MOTS-c interacts synergistically with exercise intervention to regulate PGC-1α expression, attenuate insulin resistance and enhance glucose metabolism in mice via AMPK signaling pathway
Yang, B., Yu, Q., Chang, B., Guo, Q., Xu, S.-T., Yi, X., & Cao, S. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166126 · Cited by 90 · see citing works
Long-lived animals with negligible senescence: clues for ageing research
Stenvinkel, P., & Shiels, P. G. (2019) · Biochemical Society Transactions · doi:10.1042/bst20190105 · Cited by 70 · see citing works
PGC‐1α, a potential therapeutic target against kidney aging
Lee, G.-Y., Uddin, M. J., Kim, Y., Ko, M., Yu, I., & Ha, H. (2019) · Aging Cell · doi:10.1111/acel.12994 · Cited by 71 · see citing works
(-)-Epicatechin stimulates mitochondrial biogenesis and cell growth in C2C12 myotubes via the G-protein coupled estrogen receptor
Moreno‐Ulloa, A., Miranda‐Cervantes, A., Licea-Navarro, A. F., Mansour, C. M., Beltrán‐Partida, E., Donis‐Maturano, L., la Herrán, H. C. D.-D., Villarreal, F. J., & Álvarez‐Delgado, C. (2018) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2018.01.014 · Cited by 63 · see citing works
Adiponectin treatment improves insulin resistance in mice by regulating the expression of the mitochondrial-derived peptide MOTS-c and its response to exercise via APPL1–SIRT1–PGC-1α
Guo, Q., Chang, B., Yu, Q., Xu, S.-T., Yi, X., & Cao, S. (2020) · Diabetologia · doi:10.1007/s00125-020-05269-3 · Cited by 57 · see citing works
Intermittent fasting positively modulates human gut microbial diversity and ameliorates blood lipid profile
Khan, M. N., Khan, S. I., Rana, M. I., Ayyaz, A., Khan, M. Y., & Imran, M. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.922727 · Cited by 56 · see citing works
Biomarkers of aging: from molecules and surrogates to physiology and function
Furrer, R., & Handschin, C. (2025) · Physiological Reviews · doi:10.1152/physrev.00045.2024 · Cited by 62 · see citing works
Self-citation
New Insights into Molecular Mechanisms Mediating Adaptation to Exercise; A Review Focusing on Mitochondrial Biogenesis, Mitochondrial Function, Mitophagy and Autophagy
Roberts, F. L., & Markby, G. R. (2021) · Cells · doi:10.3390/cells10102639 · Cited by 53 · see citing works
Acquired Resilience: An Evolved System of Tissue Protection in Mammals
Stone, J., Mitrofanis, J., Johnstone, D. M., Falsini, B., Bisti, S., Adam, P., Bravo‐Nuevo, A., George‐Weinstein, M., Mason, R. S., & Eells, J. T. (2018) · Dose-Response · doi:10.1177/1559325818803428 · Cited by 51 · see citing works
Neurotrophic effects of intermittent fasting, calorie restriction and exercise: a review and annotated bibliography
Mayor, E. (2023) · Frontiers in Aging · doi:10.3389/fragi.2023.1161814 · Cited by 46 · see citing works
Assessment of resveratrol, apocynin and taurine on mechanical-metabolic uncoupling and oxidative stress in a mouse model of duchenne muscular dystrophy: A comparison with the gold standard, α-methyl prednisolone
Capogrosso, R. F., Cozzoli, A., Mantuano, P., Camerino, G. M., Massari, A. M., Sblendorio, V. T., Bellis, M. D., Tamma, R., Giustino, A., Nico, B., et al. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.02.016 · Cited by 44 · see citing works
Caloric Restriction Mimetic 2-Deoxyglucose Alleviated Inflammatory Lung Injury via Suppressing Nuclear Pyruvate Kinase M2–Signal Transducer and Activator of Transcription 3 Pathway
Hu, K., Yang, Y., Lin, L., Ai, Q., Dai, J., Fan, K., Ge, P., Jiang, R., Wan, J., & Zhang, L. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00426 · Cited by 44 · see citing works
Exercise, fasting, and mimetics: toward beneficial combinations?
Jaspers, R. T., Zillikens, M. C., Friesema, E. C. H., Paoli, G. D., Bloch, W., Uitterlinden, A. G., Goglia, F., Lanni, A., & de Lange, P. (2016) · The FASEB Journal · doi:10.1096/fj.201600652r · Cited by 43 · see citing works
Pharmacological targeting of exercise adaptations in skeletal muscle: Benefits and pitfalls
Weihrauch, M., & Handschin, C. (2017) · Biochemical Pharmacology · doi:10.1016/j.bcp.2017.10.006 · Cited by 37 · see citing works
Self-citation
Concurrent Treatment with Ursolic Acid and Low-Intensity Treadmill Exercise Improves Muscle Atrophy and Related Outcomes in Rats
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
Healthy aging: A bibliometric analysis of the literature
Gu, Y., Bai, J., Chen, X., Wu, W., Liu, X., & Tan, X. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2018.11.014 · Cited by 36 · see citing works
Increased healthspan and resistance to Parkinson's disease in Drosophila by boiled and freeze-dried mature silk worm larval powder
Nguyen, P. A. H., Kim, K., Kim, A., Kim, N.-S., Kweon, H., Ji, S.-D., & Koh, Y. H. (2016) · Journal of Asia-Pacific Entomology · doi:10.1016/j.aspen.2016.05.003 · Cited by 33 · see citing works
Programming of the Beige Phenotype in White Adipose Tissue of Adult Mice by Mild Resveratrol and Nicotinamide Riboside Supplementations in Early Postnatal Life
Serrano, A., Asnani-Kishnani, M., Rodríguez, A. M., Palou, A., Ribot, J., & Bonet, M. L. (2018) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201800463 · Cited by 28 · see citing works
Skeletal muscle endothelial dysfunction through the activin A–PGC1α axis drives progression of cancer cachexia
Kim, Y.-M., Sanborn, M. A., Vijeth, S., Gajwani, P., Wang, X., Jung, D., Vályi-Nagy, T., Chakraborty, S., Mancinelli, G. E., Tóth, P. T., et al. (2025) · Nature Cancer · doi:10.1038/s43018-025-00975-6 · Cited by 27 · see citing works
In Vitro Metabolic Studies of REV-ERB Agonists SR9009 and SR9011
Geldof, L., Deventer, K., Roels, K., Tudela, E., & Eenoo, P. V. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17101676 · Cited by 27 · see citing works
Metformin and Alzheimer's disease, dementia and cognitive impairment: a systematic review protocol
Campbell, J. M., Stephenson, M., de Courten, B. V., Chapman, I. M., Bellman, S. M., & Aromataris, E. (2017) · The JBI Database of Systematic Reviews and Implementation Reports · doi:10.11124/jbisrir-2017-003380 · Cited by 26 · see citing works
Drugs, clocks and exercise in ageing: hype and hope, fact and fiction
Furrer, R., & Handschin, C. (2022) · The Journal of Physiology · doi:10.1113/jp282887 · Cited by 25 · see citing works
Self-citation
Metformin and the risk of dementia based on an analysis of 396,332 participants
Ji, S., Zhao, X., Zhu, R., Dong, Y., Huang, L., & Zhang, T. (2022) · Therapeutic Advances in Chronic Disease · doi:10.1177/20406223221109454 · Cited by 23 · see citing works
Metabolic Remodeling in Skeletal Muscle Atrophy as a Therapeutic Target
Renzini, A., Riera, C. S., Minic, I., D’Ercole, C., Lozanoska‐Ochser, B., Cedola, A., Gigli, G., Moresi, V., & Madaro, L. (2021) · Metabolites · doi:10.3390/metabo11080517 · Cited by 20 · see citing works
Role of Nuclear Receptors in Exercise-Induced Muscle AdaptationsPreprint
Kupr, B., Schnyder, S., & Handschin, C. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029835 · Cited by 22 · see citing works
Self-citation
Can exosomes transfer the preconditioning effects triggered by (poly)phenol compounds between cells?
Figueira, I., Bastos, P., González‐Sarrías, A., Espı́n, J. C., Costa‐Silva, B., & dos Santos, C. N. (2022) · Food & Function · doi:10.1039/d2fo00876a · Cited by 16 · see citing works
Exercise, exerkines and exercise mimetic drugs: Molecular mechanisms and therapeutics
Samant, V., & Prabhu, A. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.123225 · Cited by 15 · see citing works
Biomarkers of aging: functional aspects still trump molecular parameters
Furrer, R., & Handschin, C. (2025) · npj Aging · doi:10.1038/s41514-025-00207-2 · Cited by 15 · see citing works
Self-citation
Effects of ursolic acid on muscle mass and bone microstructure in rats with casting-induced muscle atrophy
Kang, Y. S., Noh, E. B., & Kim, S. H. (2019) · Physical Activity and Nutrition · doi:10.20463/jenb.2019.0022 · Cited by 14 · see citing works
Coregulator-mediated control of skeletal muscle plasticity – A mini-review
Schnyder, S., Kupr, B., & Handschin, C. (2017) · Biochimie · doi:10.1016/j.biochi.2016.12.011 · Cited by 14 · see citing works
Self-citation
Effect of resveratrol on insulin action in primary myotubes from lean individuals and individuals with severe obesity
Park, S., Jevtovic, F., Krassovskaia, P. M., Chaves, A., Zheng, D., Treebak, J. T., & Houmard, J. A. (2024) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00299.2023 · Cited by 11 · see citing works
Exercise Improves Outcomes of Surgery on Fatty Liver in Mice
Linecker, M., Frick, L. D., Kron, P., Limani, P., Kambakamba, P., Tschuor, C., Langiewicz, M., Kachaylo, E., Tian, Y., Schneider, M. A., et al. (2018) · Annals of Surgery · doi:10.1097/sla.0000000000002904 · Cited by 11 · see citing works
MOTS-c and aerobic exercise induce cardiac physiological adaptation via NRG1/ErbB4/CEBPβ modification in rats
Yuan, J., Xu, B., Ma, J., Pang, X., Fu, Y., Liang, M., Wang, M., Pan, Y., Duan, Y., Tang, M., et al. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.121330 · Cited by 10 · see citing works
Chronic low-dose REV-ERBs agonist SR9009 mitigates constant light-induced weight gain and insulin resistance via adipogenesis modulation
Yang, M., Lin, H. Y., Chen, Y. M., Hu, M., Chen, I., & Yang, C. (2025) · Biomedical Journal · doi:10.1016/j.bj.2025.100830 · Cited by 9 · see citing works
Lifestyle vs. pharmacological interventions for healthy aging
Furrer, R., & Handschin, C. (2020) · Aging · doi:10.18632/aging.102741 · Cited by 8 · see citing works
Self-citation
Greater Phosphorylation of AMPK and Multiple AMPK Substrates in the Skeletal Muscle of 24-Month-Old Calorie Restricted Compared to Ad-Libitum Fed Male Rats
Zheng, A., Kwak, S. E., Birk, J. B., Arias, E. B., Thorley, D., Wojtaszewski, J. F. P., & Cartee, G. D. (2022) · The Journals of Gerontology Series A · doi:10.1093/gerona/glac218 · Cited by 8 · see citing works
Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling
Han, L.-L., Zhang, X., Zhang, H., Li, T., Zhao, Y.-C., Tian, M., Sun, F., & Feng, B. (2024) · Journal of Chinese Integrative Medicine · doi:10.1016/j.joim.2024.01.003 · Cited by 7 · see citing works
Low-Intensity Exercise Training Additionally Increases Mitochondrial Dynamics Caused by High-Fat Diet (HFD) but Has No Additional Effect on Mitochondrial Biogenesis in Fast-Twitch Muscle by HFD
Kang, Y. S., Seong, D., Kim, J.-C., & Kim, S. H. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17155461 · Cited by 7 · see citing works
Caloric Restriction Mimetics as Priming Agents of Mesenchymal Stem Cells Secretome to Enhance Regenerative Responses to Parkinson’s Disease
Carneiro-Pereira, B., Ferreira-Antunes, F., Campos, J., Salgado, A. J., & Sampaio‐Marques, B. (2025) · Molecules · doi:10.3390/molecules30112260 · Cited by 6 · see citing works
Pharmacological targeting of age-related changes in skeletal muscle tissue
Leuchtmann, A. B., & Handschin, C. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.02.030 · Cited by 6 · see citing works
Self-citation
In silico transcriptome-based drug screening identifies celastrol as a multi-species therapeutic agent against aging-related sarcopenia and mitochondrial dysfunction
Bangfu, W., Liu, J., Zhaoyu, C., Yin, X., Mo, L., Chen, L., Chen, H., Cheng, X., Wang, Y., Liu, F., et al. (2026) · Journal of Advanced Research · doi:10.1016/j.jare.2026.01.079 · Cited by 5 · see citing works
Synthesis and evaluation of 5-aminimidazole-4-carboxamide riboside derivatives as anti-fatigue agents
Zhu, H., Zeng, W., Zhao, T., Shi, W., Dong, X., Zhang, A., Li, X., & Xu, L. (2022) · Arabian Journal of Chemistry · doi:10.1016/j.arabjc.2022.104313 · Cited by 5 · see citing works
Where and How in the mTOR Pathway Inhibitors Fight Aging: Rapamycin, Resveratrol, and Metformin
Arbor, S. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.79338 · Cited by 5 · see citing works
Phytohemagglutinin ameliorates HFD-induced obesity by increasing energy expenditure
Zhang, Y., Li, J., Wang, H. H., Li, J., Yu, Y., Li, B., Huang, L., Wu, C., & Liu, X. (2021) · Journal of Molecular Endocrinology · doi:10.1530/jme-20-0349 · Cited by 3 · see citing works
Metformin + Sodium-glucose Co-transporter-2 Inhibitor: Salutogenic Lifestyle Mimetics in a Tablet?
Kalra, S., Jacob, J. J., & Baruah, M. (2018) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/ijem.ijem_266_17 · Cited by 2 · see citing works
Autophagy Induction: A Promising Antiaging Strategy
Singh, A. K., Singh, S., & Rizvi, S. I. (2018) · Springer eBooks · doi:10.1007/978-981-13-1699-9_11 · Cited by 2 · see citing works
Mechanisms and Late-Life Intervention of Aging
Goto, S. (2019) · Springer eBooks · doi:10.1007/978-981-13-3585-3_17 · Cited by 2 · see citing works
Exercise Mimetics: An Emerging and Controversial Topic in Sport and Exercise Physiology
ElMeligie, M. M. (2022) · IntechOpen eBooks · doi:10.5772/intechopen.102533 · Cited by 3 · see citing works
Resveratrol
Powell, C. A., Zhang, J., Bowman, J. D., & Choudhury, M. (2017) · Advances in medical diagnosis, treatment, and care (AMDTC) book series · doi:10.4018/978-1-5225-2092-4.ch016 · Cited by 2 · see citing works
Exercise Mimetics: Fact Or Fantasy?
Lakshmi, G., & Sridhar, G. R. (2021) · Adipobiology · doi:10.14748/adipo.v11.8559 · Cited by 1 · see citing works
State of Knowledge and Recent Advances in Prevention and Treatment of Mitochondrial Dysfunction in Obesity and Type 2 Diabetes
Cantó, C. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-811752-1.00017-1 · Cited by 1 · see citing works
Knee Articular Cartilage: Future Directions for Research and Practice
Gahunia, H. K., Gross, A. E., & Pritzker, K. P. H. (2020) · Springer eBooks · doi:10.1007/978-1-4939-7587-7_19 · Cited by 1 · see citing works
Exercise Mimetics: Harnessing the Therapeutic Effects of Physical Activity
Labhane, M. A. (2024) · International Journal for Research in Applied Science and Engineering Technology · doi:10.22214/ijraset.2024.59159 · Cited by 1 · see citing works
Molecular control of endurance training adaptation in mouse skeletal musclePreprint
Furrer, R., Heim, B., Schmid, S., Nordström, K. J. V., Dilbaz, S., Ritz, D., Adak, V., Steurer, S. A., Walter, J., & Handschin, C. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.18.529055 · Cited by 1 · see citing works
Self-citation
Thermoregulatory and neuromuscular responses to passive heating in 42°C hot water
Rodrigues, P. (2021) · Queensland University of Technology · doi:10.5204/thesis.eprints.214197
Complex regulatory processes control exercise adaptations of skeletal muscle
(2023) · Nature Metabolism · doi:10.1038/s42255-023-00894-9
Low protein diet induced anti-cancer immune response
Bossowski, J. P. (2018) · doi:10.70675/df1b8a94z84ccz47d6z9b67zcd24191657d6

Of mice and men: the benefits of caloric restriction, exercise, and mimetics
Mercken, E. M., Carboneau, B. A., Krzysik-Walker, S. M., & de Cabo, R. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2011.11.005 · Cited by 318 · see citing works
Modulation of PGC-1α activity as a treatment for metabolic and muscle-related diseases
Svensson, K., & Handschin, C. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2014.02.013 · Cited by 13 · see citing works
Self-citation
A Literature Review of Dietary Resveratrol Supplements: Do they Mimic the Effects of Endurance Exercise?
McQuillan, N. (2013) · ScholarWorks - GVSU (Grand Valley State University) · Cited by 1 · see citing works
Exercise mimetics: molecular mechanisms, biological and therapeutic effects
Zhang, J., Shao, Q., 程腾, Lin, J., Tang, Y., Lu, H., Zhang, Y., Yu, Z., & Cao, L. (2026) · Molecular Biomedicine · doi:10.1186/s43556-026-00483-8 · Cited by 8 · see citing works
Exercise Mimetics: Fact Or Fantasy?
Lakshmi, G., & Sridhar, G. R. (2021) · Adipobiology · doi:10.14748/adipo.v11.8559 · Cited by 1 · see citing works

Authors: Handschin, C.
Affiliations: University of Basel (CH)
Corresponding author: Handschin, Christoph
ORCID: Handschin, Christoph
Venue: Pharmacological Research
Publisher: Elsevier BV
Published: 2016-01
Volume: 103
Pages: 158-166
ISSN: 1043-6618 (ISSN-L)
DOI: 10.1016/j.phrs.2015.11.009
PMC: PMC4970791
OpenAlex: W2183274960
Cited by: 72
References: 105
Citations by year: 2026: 1 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 8 · 2021: 7 · 2020: 4 · 2019: 10 · 2018: 15 · 2017: 7 · 2016: 7
FWCI: 1.02
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Pharmacological Research (publishedVersion)
PubMed (publishedVersion)
edoc (University of Basel) (acceptedVersion)
PubMed Central (acceptedVersion)
edoc (University of Basel)
Topics: Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: caloric restriction mimetics, exercise mimetics, resveratrol, PGC-1α, skeletal muscle, lifestyle intervention, diet and exercise
MeSH terms: Animals, Humans, Physical Conditioning, Animal, Drug Design, Exercise, Caloric Restriction

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

Caloric restriction and exercise “mimetics”: ready for prime time

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks