Molecular mechanisms of dietary restriction promoting health and longevity

The Hallmarks of Aging

López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982

TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival

Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914

AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint

Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849

Rapamycin fed late in life extends lifespan in genetically heterogeneous mice

Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766

Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase

Imai, S.-I., Armstrong, C. M., Kaeberlein, M., & Guarente, L. (2000) · Nature · doi:10.1038/35001622 · Cited by 3,510

Regulated Translation Initiation Controls Stress-Induced Gene Expression in Mammalian Cells

Harding, H. P., Novoa, I., Zhang, Y., Zeng, H., Wek, R. C., Schapira, M., & Ron, D. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00108-8 · Cited by 3,281

A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance

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

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

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

The genetics of ageing

Kenyon, C. J. (2010) · Nature · doi:10.1038/nature08980 · Cited by 2,739

mTOR at the nexus of nutrition, growth, ageing and disease

Liu, G. Y., & Sabatini, D. M. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0199-y · Cited by 2,737

Mechanisms, regulation and functions of the unfolded protein response

Hetz, C., Zhang, K., & Kaufman, R. J. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0250-z · Cited by 2,666

Obesity and Metabolic Syndrome in Circadian Clock Mutant Mice

Turek, F. W., Joshu, C., Kohsaka, A., Lin, E., Ivanova, G., McDearmon, E., Laposky, A., Losee-Olson, S., Easton, A., Jensen, D. R., et al. (2005) · Science · doi:10.1126/science.1108750 · Cited by 2,485

Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB

Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J.-H., Hsu, P. P., Bagley, A. F., Markhard, A. L., & Sabatini, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.029 · Cited by 2,365

daf-2 , an Insulin Receptor-Like Gene That Regulates Longevity and Diapause in Caenorhabditis elegans

Kimura, K. D., Tissenbaum, H. A., Liu, Y., & Ruvkun, G. (1997) · Science · doi:10.1126/science.277.5328.942 · Cited by 2,250

FGF-21 as a novel metabolic regulator

Kharitonenkov, A., Shiyanova, T. L., Koester, A., Ford, A. M., Micanovic, R., Galbreath, E. J., Sandusky, G. E., Hammond, L. J., Moyers, J. S., Owens, R. A., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23606 · Cited by 2,125

IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice

Holzenberger, M., Dupont, J., Ducos, B., Leneuve, P., Géloën, A., Even, P. C., Cervera, P., & Le Bouc, Y. (2003) · Nature · doi:10.1038/nature01298 · Cited by 2,109

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

Sirtuins as regulators of metabolism and healthspan

Houtkooper, R. H., Pirinen, E., & Auwerx, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3293 · Cited by 2,008

Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet

Hatori, M., Vollmers, C., Zarrinpar, A., DiTacchio, L., Bushong, E. A., Gill, S., Leblanc, M., Chaix, A., Joens, M., Fitzpatrick, J. A. J., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.019 · Cited by 1,986

Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase

Cohen, H. Y., Miller, C., Bitterman, K. J., Wall, N. R., Hekking, B., Kessler, B., Howitz, K. T., Gorospe, M., de Cabo, R., & Sinclair, D. A. (2004) · Science · doi:10.1126/science.1099196 · Cited by 1,924

Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor

Shimazu, T., Hirschey, M. D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C. A., Lim, H., Saunders, L. R., Stevens, R. D., et al. (2013) · Science · doi:10.1126/science.1227166 · Cited by 1,777

Requirement of NAD and SIR2 for Life-Span Extension by Calorie Restriction in Saccharomyces cerevisiae

Lin, S.-J., Defossez, P.-A., & Guarente, L. (2000) · Science · doi:10.1126/science.289.5487.2126 · Cited by 1,775

Extension of murine life span by overexpression of catalase targeted to mitochondria

Schriner, S. E., Linford, N. J., Martin, G. M., Treuting, P., Ogburn, C. E., Emond, M., Coskun, P. E., Ladiges, W., Wolf, N., Van Remmen, H., et al. (2005) · Science · doi:10.1126/science.1106653 · Cited by 1,724

Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells

Vattem, K. M., & Wek, R. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400541101 · Cited by 1,696

mTOR is a key modulator of ageing and age-related disease

Johnson, S. C., Rabinovitch, P. S., & Kaeberlein, M. (2013) · Nature · doi:10.1038/nature11861 · Cited by 1,676

A Mutant Drosophila Insulin Receptor Homolog That Extends Life-Span and Impairs Neuroendocrine Function

Tatar, M., Kopelman, A. H., Epstein, D., Tu, M., Yin, C. ‐., & Garofalo, R. S. (2001) · Science · doi:10.1126/science.1057987 · Cited by 1,630

NAD+ metabolism and its roles in cellular processes during ageing

Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00313-x · Cited by 1,617

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

Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes

Sutton, E. F., Beyl, R., Early, K. S., Cefalu, W. T., Ravussin, E., & Peterson, C. M. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.04.010 · Cited by 1,531

NAD+ and sirtuins in aging and disease

Imai, S.-I., & Guarente, L. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.04.002 · Cited by 1,481

Extension of Life-Span by Loss of CHICO, a Drosophila Insulin Receptor Substrate Protein

Clancy, D. J., Gems, D., Harshman, L. G., Oldham, S., Stocker, H., Hafen, E., Leevers, S. J., & Partridge, L. (2001) · Science · doi:10.1126/science.1057991 · Cited by 1,436

Sirt5 Is a NAD-Dependent Protein Lysine Demalonylase and Desuccinylase

Du, J., Zhou, Y., Su, X., Yu, J. J., Khan, S., Jiang, H., Kim, J., Woo, J., Kim, J. H., Choi, B. H., et al. (2011) · Science · doi:10.1126/science.1207861 · Cited by 1,429

p53 Target Genes Sestrin1 and Sestrin2 Connect Genotoxic Stress and mTOR Signaling

Budanov, A. V., & Karin, M. (2008) · Cell · doi:10.1016/j.cell.2008.06.028 · Cited by 1,326

Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients

Kaeberlein, M., Powers, R. W., Steffen, K. K., Westman, E. A., Hu, D., Dang, N., Kerr, E. O., Kirkland, K. T., Fields, S., & Kennedy, B. K. (2005) · Science · doi:10.1126/science.1115535 · Cited by 1,293

Promoting Health and Longevity through Diet: From Model Organisms to Humans

Fontana, L., & Partridge, L. (2015) · Cell · doi:10.1016/j.cell.2015.02.020 · Cited by 1,245

Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States

Mattson, M. P., & Arumugam, T. V. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.05.011 · Cited by 1,242

Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress

Schulz, T. J., Zarse, K., Voigt, A., Urban, N., Birringer, M., & Ristow, M. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.08.011 · Cited by 1,209

Rapamycin-Induced Insulin Resistance Is Mediated by mTORC2 Loss and Uncoupled from Longevity

Lamming, D. W., Ye, L., Katajisto, P., Goncalves, M. D., Saitoh, M., Stevens, D. M., Davis, J. G., Salmon, A. B., Richardson, A., Ahima, R. S., et al. (2012) · Science · doi:10.1126/science.1215135 · Cited by 1,199

Impact of intermittent fasting on health and disease processes

Mattson, M. P., Longo, V. D., & Harvie, M. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.10.005 · Cited by 1,187

SIRT4 Inhibits Glutamate Dehydrogenase and Opposes the Effects of Calorie Restriction in Pancreatic β Cells

Haigis, M. C., Mostoslavsky, R., Haigis, K. M., Fahie, K., Christodoulou, D. C., Murphy, A. J., Valenzuela, D. M., Yancopoulos, G. D., Karow, M., Blander, G., et al. (2006) · Cell · doi:10.1016/j.cell.2006.06.057 · Cited by 1,162

Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue

Blüher, M., Kahn, B. B., & Kahn, C. R. (2003) · Science · doi:10.1126/science.1078223 · Cited by 1,155

Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction

Someya, S., Yu, W., Hallows, W. C., Xu, J., Vann, J. M., Leeuwenburgh, C., Tanokura, M., Denu, J. M., & Prolla, T. A. (2010) · Cell · doi:10.1016/j.cell.2010.10.002 · Cited by 1,150

Ribosomal Protein S6 Kinase 1 Signaling Regulates Mammalian Life Span

Selman, C., Tullet, J. M. A., Wieser, D., Irvine, E., Lingard, S. J., Choudhury, A. I., Claret, M., Al-Qassab, H., Carmignac, D., Ramadani, F., et al. (2009) · Science · doi:10.1126/science.1177221 · Cited by 1,120

Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS

Nisoli, E., Tonello, C., Cardile, A., Cozzi, V., Bracale, R., Tedesco, L., Falcone, S., Valerio, A., Cantoni, O., Clementi, E., et al. (2005) · Science · doi:10.1126/science.1117728 · Cited by 1,107

Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41)

Kimura, I., Inoue, D., Maeda, T., Hara, T., Ichimura, A., Miyauchi, S., Kobayashi, M., Hirasawa, A., & Tsujimoto, G. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016088108 · Cited by 1,106

Dwarf mice and the ageing process

Brown‐Borg, H. M., Borg, K. E., Meliska, C. J., & Bartke, A. (1996) · Nature · doi:10.1038/384033a0 · Cited by 1,091

SIRT6 Links Histone H3 Lysine 9 Deacetylation to NF-κB-Dependent Gene Expression and Organismal Life Span

Kawahara, T. L. A., Michishita, E., Adler, A. S., Damian, M., Berber, E., Lin, M., McCord, R. A., Ongaigui, K. C. L., Boxer, L. D., Chang, H. Y., et al. (2009) · Cell · doi:10.1016/j.cell.2008.10.052 · Cited by 1,090

The sirtuin SIRT6 regulates lifespan in male mice

Kanfi, Y., Naiman, S., Amir, G., Peshti, V., Zinman, G., Nahum, L., Bar-Joseph, Z., & Cohen, H. Y. (2012) · Nature · doi:10.1038/nature10815 · Cited by 1,059

BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis

Rudic, R. D., McNamara, P., Curtis, A.-M., Boston, R. C., Panda, S., Hogenesch, J. B., & FitzGerald, G. A. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020377 · Cited by 1,059

Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila Melanogaster

Bjedov, I., Toivonen, J. M., Kerr, F., Slack, C., Jacobson, J., Foley, A., & Partridge, L. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2009.11.010 · Cited by 1,057

Hormone-fuel interrelationships during fasting.

Cahill, G. F., Herrera, M. G., Morgan, A. P., Soeldner, J. S., Steinke, J., Levy, P. L., Reichard, G. A., & Kipnis, D. M. (1966) · Journal of Clinical Investigation · doi:10.1172/jci105481 · Cited by 1,036

A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility.

Friedman, D. B., & Johnson, T. E. (1988) · Genetics · doi:10.1093/genetics/118.1.75 · Cited by 1,011

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

Circadian timing of food intake contributes to weight gain

Arble, D. M., Bass, J., Laposky, A. D., Vitaterna, M. H., & Turek, F. W. (2009) · Obesity · doi:10.1038/oby.2009.264 · Cited by 953

Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases

Bjelakovic, G., Nikolova, D., Gluud, L. L., Simonetti, R. G., & Gluud, C. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007176.pub2 · Cited by 924

The Ratio of Macronutrients, Not Caloric Intake, Dictates Cardiometabolic Health, Aging, and Longevity in Ad Libitum-Fed Mice

Solon-Biet, S. M., McMahon, A. C., Ballard, J. W. O., Ruohonen, K., Wu, L. E., Cogger, V. C., Warren, A., Huang, X., Pichaud, N., Melvin, R. G., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.02.009 · Cited by 904

The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes

Gaich, G., Chien, J. Y., Fu, H., Glass, L. C., Deeg, M. A., Holland, W. L., Kharitonenkov, A., Bumol, T., Schilske, H. K., & Moller, D. E. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.08.005 · Cited by 885

SIRT6 Promotes DNA Repair Under Stress by Activating PARP1

Mao, Z., Hine, C., Tian, X., Van Meter, M., Au, M., Vaidya, A., Seluanov, A., & Gorbunova, V. (2011) · Science · doi:10.1126/science.1202723 · Cited by 867

A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and healthspan

Brandhorst, S., Choi, I. Y., Wei, M., Cheng, C. W., Sedrakyan, S., Navarrete, G., Dubeau, L., Yap, L. P., Park, R., Vinciguerra, M., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.012 · Cited by 850

Identification of a novel FGF, FGF-21, preferentially expressed in the liver

Nishimura, T., Nakatake, Y., Konishi, M., & Itoh, N. (2000) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(00)00067-1 · Cited by 847

Caloric restriction improves health and survival of rhesus monkeys

Mattison, J. A., Colman, R. J., Beasley, T. M., Allison, D. B., Kemnitz, J. W., Roth, G. S., Ingram, D. K., Weindruch, R., de Cabo, R., & Anderson, R. M. (2017) · Nature Communications · doi:10.1038/ncomms14063 · Cited by 838

Regulation of Immune Responses by mTOR

Powell, J. D., Pollizzi, K. N., Heikamp, E. B., & Horton, M. R. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075024 · Cited by 836

Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production

Flurkey, K., Papaconstantinou, J., Miller, R. A., & Harrison, D. E. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111158898 · Cited by 826

Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans

Hansen, M., Taubert, S., Crawford, D., Libina, N., Lee, S., & Kenyon, C. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2006.00267.x · Cited by 803

Caloric restriction

Speakman, J. R., & Mitchell, S. E. (2011) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2011.07.001 · Cited by 800

Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans

Civitarese, A. E., Carling, S., Heilbronn, L. K., Hulver, M. H., Ukropcova, B., Deutsch, W. A., Smith, S. R., & Ravussin, E. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040076 · Cited by 790

How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis)

Ristow, M., & Zarse, K. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.03.014 · Cited by 789

SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle

Nakagawa, T., Lomb, D. J., Haigis, M. C., & Guarente, L. (2009) · Cell · doi:10.1016/j.cell.2009.02.026 · Cited by 787

Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila

Grandison, R. C., Piper, M. D. W., & Partridge, L. (2009) · Nature · doi:10.1038/nature08619 · Cited by 785

Phosphorylation of initiation factor 2α by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast

Dever, T. E., Feng, L., Wek, R. C., Cigan, A. M., Donahue, T. F., & Hinnebusch, A. G. (1992) · Cell · doi:10.1016/0092-8674(92)90193-g · Cited by 776

Autophagy as a promoter of longevity: insights from model organisms

Hansen, M., Rubinsztein, D. C., & Walker, D. W. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0033-y · Cited by 754

mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake

Yilmaz, Ö. H., Katajisto, P., Lamming, D. W., Gültekin, Y., Bauer-Rowe, K. E., Sengupta, S., Birsoy, K., Dursun, A., Yilmaz, V. O., Selig, M., et al. (2012) · Nature · doi:10.1038/nature11163 · Cited by 753

The first identification of lysine malonylation substrates and its regulatory enzyme

Peng, C., Lu, Z., Xie, Z., Cheng, Z., Chen, Y., Tan, M., Luo, H., Zhang, Y., He, W., Yang, K., et al. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.012658 · Cited by 751

Sirt1 Extends Life Span and Delays Aging in Mice through the Regulation of Nk2 Homeobox 1 in the DMH and LH

Satoh, A., Brace, C. S., Rensing, N., Cliften, P. F., Wozniak, D. F., Herzog, E. D., Yamada, K. A., & Imai, S. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.07.013 · Cited by 747

Caloric Intake and Aging

Weindruch, R. H., & Sohal, R. S. (1997) · New England Journal of Medicine · doi:10.1056/nejm199710023371407 · Cited by 743

Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae

Anderson, R. M., Bitterman, K. J., Wood, J. G., Medvedik, O., & Sinclair, D. A. (2003) · Nature · doi:10.1038/nature01578 · Cited by 736

Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging

Van Remmen, H., Ikeno, Y., Hamilton, M., Pahlavani, M., Wolf, N., Thorpe, S. R., Alderson, N. L., Baynes, J. W., Epstein, C. J., Huang, T.-T., et al. (2003) · Physiological Genomics · doi:10.1152/physiolgenomics.00122.2003 · Cited by 734

Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell Types to Chemotherapy

Lee, C. D., Raffaghello, L., Brandhorst, S., Safdie, F. M., Bianchi, G., Martín‐Montalvo, A., Pistoia, V., Wei, M., Hwang, S., Merlino, A., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003293 · Cited by 734

Meal timing and frequency: implications for cardiovascular disease prevention: A scientific statement from the american heart association

St-Onge, M.-P., Ard, J., Baskin, M. L., Chiuve, S. E., Johnson, H. M., Kris-Etherton, P., & Varady, K. (2017) · Circulation · doi:10.1161/cir.0000000000000476 · Cited by 728

SIRT1 transgenic mice show phenotypes resembling calorie restriction

Bordone, L., Cohen, D., Robinson, A., Motta, M. C., Van Veen, E., Czopik, A., Steele, A. D., Crowe, H., Marmor, S., Luo, J., et al. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00335.x · Cited by 722

SIRT3, a Mitochondrial Sirtuin Deacetylase, Regulates Mitochondrial Function and Thermogenesis in Brown Adipocytes

Shi, T., Wang, F., Stieren, E., & Tong, Q. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414670200 · Cited by 712

The GCN2‐ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivation

Ye, J., Kumanova, M., Hart, L. S., Sloane, K. L., Zhang, H., Panis, D. N. D., Bobrovnikova-Marjon, E. V., Diehl, J. A., Ron, D., & Koumenis, C. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.81 · Cited by 709

Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency

López-Lluch, G., Hunt, N., Jones, B., Zhu, M., Jamieson, H., Hilmer, S., Cascajo, M. V., Allard, J., Ingram, D. K., Navas, P., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510452103 · Cited by 699

Methionine‐deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF‐I and insulin levels, and increases hepatocyte MIF levels and stress resistance

Miller, R. A., Buehner, G., Chang, Y., Harper, J. M., Sigler, R., & Smith‐Wheelock, M. (2005) · Aging Cell · doi:10.1111/j.1474-9726.2005.00152.x · Cited by 681

(d)-β-Hydroxybutyrate Inhibits Adipocyte Lipolysis via the Nicotinic Acid Receptor PUMA-G

Taggart, A. K. P., Kero, J. T., Gan, X., Cai, T., Cheng, K., Ippolito, M. C., Ren, N., Kaplan, R. A., Wu, K., Wu, T.-J., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c500213200 · Cited by 673

CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life

Elchuri, S., Oberley, T. D., Qi, W., Eisenstein, R. S., Jackson Roberts, L., Van Remmen, H., Epstein, C. J., & Huang, T.-T. (2005) · Oncogene · doi:10.1038/sj.onc.1208207 · Cited by 667

Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota

Li, G., Xie, C., Lu, S., Nichols, R. G., Tian, Y., Li, L., Patel, D., Ma, Y., Brocker, C. N., Yan, T., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.019 · Cited by 667

TOR Signaling and Rapamycin Influence Longevity by Regulating SKN-1/Nrf and DAF-16/FoxO

Robida-Stubbs, S., Glover-Cutter, K., Lamming, D. W., Mizunuma, M., Narasimhan, S. D., Neumann-Haefelin, E., Sabatini, D. M., & Blackwell, T. K. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.007 · Cited by 648

Sirt7 Increases Stress Resistance of Cardiomyocytes and Prevents Apoptosis and Inflammatory Cardiomyopathy in Mice

Vakhrusheva, O., Smolka, C., Gajawada, P., Sawa Kostin, D., Boettger, T., Kubin, T., Braun, T. W., & Bober, E. (2008) · Circulation Research · doi:10.1161/circresaha.107.164558 · Cited by 646

Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial

Trepanowski, J. F., Kroeger, C. M., Barnosky, A., Klempel, M. C., Bhutani, S., Hoddy, K. K., Gabel, K., Freels, S., Rigdon, J., Rood, J., et al. (2017) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2017.0936 · Cited by 645

Activation of the Protein Deacetylase SIRT6 by Long-chain Fatty Acids and Widespread Deacylation by Mammalian Sirtuins

Feldman, J. L., Baeza, J., & Denu, J. M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.c113.511261 · Cited by 637

Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome

Hebert, A. S., Dittenhafer-Reed, K. E., Yu, W., Bailey, D. J., Selen, E. S., Boersma, M. D., Carson, J. J., Tonelli, M., Balloon, A. J., Higbee, A. J., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.10.024 · Cited by 636

Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila

Burnett, C., Valentini, S., Cabreiro, F., Goss, M., Somogyvári, M., Piper, M. D., Hoddinott, M., Sutphin, G. L., Leko, V., McElwee, J. J., et al. (2011) · Nature · doi:10.1038/nature10296 · Cited by 624

TBC1D7 Is a Third Subunit of the TSC1-TSC2 Complex Upstream of mTORC1

Dibble, C. C., Elis, W., Menon, S., Qin, W., Klekota, J., Asara, J. M., Finan, P. M., Kwiatkowski, D. J., Murphy, L. O., & Manning, B. D. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.06.009 · Cited by 612

Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer

Herranz, D., Muñoz-Martin, M., Cañamero, M., Mulero, F., Martinez-Pastor, B., Fernandez-Capetillo, O., & Serrano, M. (2010) · Nature Communications · doi:10.1038/ncomms1001 · Cited by 612

Assessment of Growth Parameters and Life Span of GHR/BP Gene-Disrupted Mice 1

Coschigano, K. T., Clemmons, D., Bellush, L. L., & Kopchick, J. J. (2000) · Endocrinology · doi:10.1210/endo.141.7.7586 · Cited by 611

Low methionine ingestion by rats extends life span.

Orentreich, N., Matias, J. R., Felice, A. D., & Zimmerman, J. (1993) · Journal of NutriLife · doi:10.1093/jn/123.2.269 · Cited by 608

SAMTOR is an S -adenosylmethionine sensor for the mTORC1 pathway

Gu, X., Orozco, J. M., Saxton, R. A., Condon, K. J., Liu, G. Y., Krawczyk, P. A., Scaria, S. M., Harper, J. W., Gygi, S. P., & Sabatini, D. M. (2017) · Science · doi:10.1126/science.aao3265 · Cited by 598

FGF21 is an endocrine signal of protein restriction

Laeger, T., Henagan, T. M., Albarado, D. C., Redman, L. M., Bray, G. A., Noland, R. C., Münzberg, H., Hutson, S. M., Gettys, T. W., Schwartz, M. W., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci74915 · Cited by 593

Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans

Greer, E. L., & Brunet, A. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00459.x · Cited by 591

Endogenous hydrogen sulfide production is essential for dietary restriction benefits

Hine, C., Harputlugil, E., Zhang, Y., Ruckenstuhl, C., Lee, B. C., Brace, L., Longchamp, A., Treviño-Villarreal, J. H., Mejia, P., Ozaki, C. K., et al. (2015) · Cell · doi:10.1016/j.cell.2014.11.048 · Cited by 558

Effects of Time-Restricted Eating on Weight Loss and Other Metabolic Parameters in Women and Men With Overweight and Obesity: The TREAT Randomized Clinical Trial

Lowe, D. A., Wu, N., Rohdin-Bibby, L., Moore, A. H., Kelly, N., Liu, Y. E., Philip, E., Vittinghoff, E., Heymsfield, S. B., Olgin, J. E., et al. (2020) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2020.4153 · Cited by 553

Meal frequency and timing in health and disease

Mattson, M. P., Allison, D. B., Fontana, L., Harvie, M., Longo, V. D., Malaisse, W. J., Mosley, M., Notterpek, L. M., Ravussin, É., Scheer, F. A. J. L., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1413965111 · Cited by 552

Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40

Yang, H., Jiang, X., Li, B., Yang, H. J., Miller, M., Yang, A., Dhar, A., & Pavletich, N. P. (2017) · Nature · doi:10.1038/nature25023 · Cited by 548

Uncharged tRNA Activates GCN2 by Displacing the Protein Kinase Moiety from a Bipartite tRNA-Binding Domain

Dong, J., Qiu, H., Garcia-Barrio, M., Anderson, J., & Hinnebusch, A. G. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00028-9 · Cited by 545

Evidence for lifespan extension and delayed age–related biomarkers in insulin receptor substrate 1 null mice

Selman, C., Lingard, S., Choudhury, A. I., Batterham, R. L., Claret, M., Clements, M., Ramadani, F., Okkenhaug, K., Schuster, E., Blanc, E., et al. (2008) · The FASEB Journal · doi:10.1096/fj.07-9261com · Cited by 532

Calories Do Not Explain Extension of Life Span by Dietary Restriction in Drosophila

Mair, W. B., Piper, M. D. W., & Partridge, L. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030223 · Cited by 528

Brain IRS2 Signaling Coordinates Life Span and Nutrient Homeostasis

Taguchi, A., Wartschow, L. M., & White, M. F. (2007) · Science · doi:10.1126/science.1142179 · Cited by 523

A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms

Choi, I. Y., Piccio, L. M., Childress, P., Bollman, B., Ghosh, A., Brandhorst, S., Suarez, J., Michalsen, A., Cross, A. H., Morgan, T. E., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.009 · Cited by 513

Deletion, But Not Antagonism, of the Mouse Growth Hormone Receptor Results in Severely Decreased Body Weights, Insulin, and Insulin-Like Growth Factor I Levels and Increased Life Span

Coschigano, K. T., Holland, A. N., Riders, M. E., List, E. O., Flyvbjerg, A., & Kopchick, J. J. (2003) · Endocrinology · doi:10.1210/en.2003-0374 · Cited by 510

Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening

Liao, C., Rikke, B. A., Johnson, T. E., Diaz, V., & Nelson, J. F. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2009.00533.x · Cited by 501

LINE1 Derepression in aged wild-type and SIRT6-deficient mice drives inflammation

Simon, M., Van Meter, M., Ablaeva, J., Ke, Z., Gonzalez, R. S., Taguchi, T., De Cecco, M., Leonova, K. I., Kogan, V., Helfand, S. L., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.02.014 · Cited by 498

Impairment of an endothelial NAD(+)-H2S signaling network is a reversible cause of vascular aging

Das, A., Huang, G. X., Bonkowski, M. S., Longchamp, A., Li, C., Schultz, M. B., Kim, L.-J., Osborne, B., Joshi, S., Lu, Y., et al. (2018) · Cell · doi:10.1016/j.cell.2018.02.008 · Cited by 496

Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression

Cheng, C., Adams, G. B., Perin, L., Wei, M., Zhou, X., Lam, B. S., Sacco, S. D., Mirisola, M. G., Quinn, D. I., Dorff, T. B., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.04.014 · Cited by 491

The Histidyl-tRNA Synthetase-Related Sequence in the eIF-2α Protein Kinase GCN2 Interacts with tRNA and Is Required for Activation in Response to Starvation for Different Amino Acids

Wek, S. A., Zhu, S., & Wek, R. C. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.8.4497 · Cited by 487

MicroRNA 217 Modulates Endothelial Cell Senescence via Silent Information Regulator 1

Menghini, R., Casagrande, V., Cardellini, M., Martelli, E., Terrinoni, A., Amati, F., Vasa‐Nicotera, M., Ippoliti, A., Novelli, G., Melino, G., et al. (2009) · Circulation · doi:10.1161/circulationaha.109.864629 · Cited by 485

Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice

Bitto, A., Ito, T. K., Pineda, V. V., LeTexier, N. J., Huang, H. Z., Sutlief, E., Tung, H., Vizzini, N., Chen, B., Smith, K., et al. (2016) · eLife · doi:10.7554/elife.16351 · Cited by 474

Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival

Efeyan, A., Zoncu, R., Chang, S. H., Gumper, I., Snitkin, H., Wolfson, R. L., Kirak, O., Sabatini, D. M., & Sabatini, D. M. (2012) · Nature · doi:10.1038/nature11745 · Cited by 473

Decreased consumption of branched-chain amino acids improves metabolic health

Fontana, L., Cummings, N. E., Arriola Apelo, S. I., Neuman, J. C., Kasza, I., Schmidt, B. A., Cava, E., Spelta, F., Tosti, V., Syed, F. A., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.092 · Cited by 466

Update on the oxidative stress theory of aging: Does oxidative stress play a role in aging or healthy aging?

Salmon, A. B., Richardson, A. G., & Pérez, V. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.12.015 · Cited by 451

Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice

Mitchell, S. J., Madrigal-Matute, J., Scheibye-Knudsen, M., Fang, E., Aon, M., González-Reyes, J. A., Cortassa, S., Kaushik, S., Gonzalez-Freire, M., Patel, B., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.027 · Cited by 451

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

Lower protein content in infant formula reduces BMI and obesity risk at school age: follow-up of a randomized trial

Weber, M., Grote, V., Closa‐Monasterolo, R., Escribano, J., Langhendries, J., Dain, E., Giovannini, M., Verduci, E., Gruszfeld, D., Socha, P., et al. (2014) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.113.064071 · Cited by 443

SIRT3 Reverses Aging-Associated Degeneration

Brown, K., Xie, S., Qiu, X., Mohrin, M., Shin, J., Liu, Y., Zhang, D., Scadden, D. T., & Chen, D. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.01.005 · Cited by 436

Sirt1 modulates premature senescence-like phenotype in human endothelial cells

Ota, H., Akishita, M., Eto, M., Iijima, K., Kaneki, M., & Ouchi, Y. (2007) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2007.08.008 · Cited by 429

Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging

Mihaylova, M. M., Cheng, C.-W., Cao, A. Q., Tripathi, S., Mana, M. D., Bauer-Rowe, K. E., Abu-Remaileh, M., Clavain, L., Erdemir, A., Lewis, C. A., et al. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.04.001 · Cited by 428

Extending the Lifespan of Long-Lived Mice

Bartke, A., Wright, J. C., Mattison, J. A., Ingram, D. K., Miller, R. A., & Roth, G. S. (2001) · Nature · doi:10.1038/35106646 · Cited by 422

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

Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity

Biase, S. D., Lee, C. D., Brandhorst, S., Manes, B., Buono, R., Cheng, C., Cacciottolo, M., Martín‐Montalvo, A., de Cabo, R., Wei, M., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.06.005 · Cited by 418

Fasting and cancer treatment in humans: A case series report

Safdie, F. M., Dorff, T. B., Quinn, D. I., Fontana, L., Wei, M., Lee, C. D., Cohen, P., & Longo, V. D. (2009) · Aging · doi:10.18632/aging.100114 · Cited by 410

Extracellular vesicle-contained eNAMPT delays aging and extends lifespan in mice

Yoshida, M., Satoh, A., Lin, J. B., Mills, K. F., Sasaki, Y., Rensing, N., Wong, M., Apte, R. S., & Imai, S.-I. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.05.015 · Cited by 407

The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine

Yu, D., Richardson, N. E., Green, C. L., Spicer, A. B., Trautman, M. E., Flores, V., Jang, C., Kasza, I., Nikodémová, M., Wakai, M. H., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.03.025 · Cited by 397

Long-term caloric restriction ameliorates the decline in diastolic function in humans

Meyer, T. E., Kovács, S. J., Ehsani, A. A., Klein, S., Holloszy, J. O., & Fontana, L. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.08.069 · Cited by 383

Rictor/TORC2 regulates fat metabolism, feeding, growth, and life span in Caenorhabditis elegans

Soukas, A. A., Kane, E. A., Carr, C. E., Melo, J. A., & Ruvkun, G. (2009) · Genes & Development · doi:10.1101/gad.1775409 · Cited by 380

Caloric Restriction, the Traditional Okinawan Diet, and Healthy Aging: The Diet of the World's Longest‐Lived People and Its Potential Impact on Morbidity and Life Span

WILLCOX, B. J., WILLCOX, D. C., TODORIKI, H., FUJIYOSHI, A., YANO, K., HE, Q., CURB, J. D., & SUZUKI, M. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1396.037 · Cited by 370

Fasting-mimicking diet and hormone therapy induce breast cancer regression

Caffa, I., Spagnolo, V., Vernieri, C., Valdemarin, F., Becherini, P., Wei, M., Brandhorst, S., Zucal, C., Driehuis, E., Ferrando, L., et al. (2020) · Nature · doi:10.1038/s41586-020-2502-7 · Cited by 366

High-Fat Diet Triggers Inflammation-Induced Cleavage of SIRT1 in Adipose Tissue To Promote Metabolic Dysfunction

Chalkiadaki, A., & Guarente, L. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.07.003 · Cited by 356

Recruitment of folliculin to lysosomes supports the amino acid–dependent activation of Rag GTPases

Petit, C. S., Roczniak-Ferguson, A., & Ferguson, S. M. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201307084 · Cited by 355

Type 5 Adenylyl Cyclase Disruption Increases Longevity and Protects Against Stress

Yan, L., Vatner, D. E., O’Connor, J. P., Ivessa, A., Ge, H., Chen, W., Hirotani, S., Ishikawa, Y., Sadoshima, J., & Vatner, S. F. (2007) · Cell · doi:10.1016/j.cell.2007.05.038 · Cited by 354

KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1

Wolfson, R. L., Chantranupong, L., Wyant, G. A., Gu, X., Orozco, J. M., Shen, K., Condon, K. J., Petri, S., Kedir, J. F., Scaria, S. M., et al. (2017) · Nature · doi:10.1038/nature21423 · Cited by 345

Restoration of metabolic health by decreased consumption of branched‐chain amino acids

Richardson, N. E., Williams, E. M., Kasza, I., Konon, E. N., Schaid, M. D., Schmidt, B., Poudel, C., Sherman, D. S., Yu, D., Apelo, S. I. A., et al. (2017) · The Journal of Physiology · doi:10.1113/jp275075 · Cited by 339

Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial

de Groot, S., Lugtenberg, R. T., Cohen, D., Welters, M. J. P., Ehsan, I., Vreeswijk, M. P. G., Smit, V. T. H. B. M., de Graaf, H., Heijns, J. B., Portielje, J. E. A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16138-3 · Cited by 338

Fasting-Mimicking Diet Promotes Ngn3-Driven β-Cell Regeneration to Reverse Diabetes

Cheng, C., Villani, V., Buono, R., Wei, M., Kumar, S., Yilmaz, Ö. H., Cohen, P., Sneddon, J. B., Perin, L., & Longo, V. D. (2017) · Cell · doi:10.1016/j.cell.2017.01.040 · Cited by 335

A randomized pilot study comparing zero‐calorie alternate‐day fasting to daily caloric restriction in adults with obesity

Catenacci, V. A., Pan, Z., Ostendorf, D., Brannon, S., Gozansky, W. S., Mattson, M. P., Martin, B., MacLean, P. S., Melanson, E. L., & Troy Donahoo, W. (2016) · Obesity · doi:10.1002/oby.21581 · Cited by 332

The effect of fasting or calorie restriction on autophagy induction: A review of the literature

Bagherniya, M., Butler, A. E., Barreto, G. E., & Sahebkar, A. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.08.004 · Cited by 328

Branched-chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control

Solon‐Biet, S. M., Cogger, V. C., Pulpitel, T., Wahl, D., Clark, X., Bagley, E. E., Gregoriou, G. C., Senior, A. M., Wang, Q., Brandon, A. E., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0059-2 · Cited by 327

Calorie restriction increases fatty acid synthesis and whole body fat oxidation rates

Bruss, M. D., Khambatta, C. F., Ruby, M. A., Aggarwal, I., & Hellerstein, M. K. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00524.2009 · Cited by 321

Hepatic Sirt1 deficiency in mice impairs mTorc2/Akt signaling and results in hyperglycemia, oxidative damage, and insulin resistance

Wang, R.-H., Kim, H., Xiao, C., Xu, X., Gavrilova, O., & Deng, C. (2011) · Journal of Clinical Investigation · doi:10.1172/jci46243 · Cited by 315

The amino acid sensor GCN2 controls gut inflammation by inhibiting inflammasome activation

Ravindran, R., Loebbermann, J., Nakaya, H. I., Khan, N., Ma, H., Gama, L., Machiah, D. K., Lawson, B., Hakimpour, P., Wang, Y.-C., et al. (2016) · Nature · doi:10.1038/nature17186 · Cited by 312

Increased Mammalian Lifespan and a Segmental and Tissue-Specific Slowing of Aging after Genetic Reduction of mTOR Expression

Wu, J. J., Liu, J., Chen, E. B., Wang, J. J., Cao, L., Narayan, N., Fergusson, M. M., Rovira, I. I., Allen, M., Springer, D. A., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.07.030 · Cited by 307

Daily Fasting Improves Health and Survival in Male Mice Independent of Diet Composition and Calories

Mitchell, S. J., Bernier, M., Mattison, J. A., Aon, M. A., Kaiser, T. A., Anson, R. M., Ikeno, Y., Anderson, R. M., Ingram, D. K., & de Cabo, R. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.08.011 · Cited by 305

Delayed Occurrence of Fatal Neoplastic Diseases in Ames Dwarf Mice: Correlation to Extended Longevity

Ikeno, Y., Bronson, R. T., Hubbard, G. B., Lee, S., & Bartke, A. (2003) · The Journals of Gerontology Series A · doi:10.1093/gerona/58.4.b291 · Cited by 298

Somatotropic Signaling: Trade-Offs Between Growth, Reproductive Development, and Longevity

Bartke, A., Sun, L. Y., & Longo, V. D. (2013) · Physiological Reviews · doi:10.1152/physrev.00006.2012 · Cited by 296

Dynamic regulation of PGC‐1α localization and turnover implicates mitochondrial adaptation in calorie restriction and the stress response

Anderson, R. M., Barger, J. L., Edwards, M. G., Braun, K. H., O’Connor, C. E., Prolla, T. A., & Weindruch, R. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2007.00357.x · Cited by 283

Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly

Rose, G., Dato, S., Altomare, K., Bellizzi, D., Garasto, S., Greco, V, Passarino, G., Feraco, E., Mari, V, Barbi, C., et al. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(03)00209-2 · Cited by 282

Effects of intermittent feeding upon body weight and lifespan in inbred mice: interaction of genotype and age

Goodrick, C. L., Ingram, D. K., Reynolds, M. A., Freeman, J. R., & Cider, N. (1990) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(90)90107-q · Cited by 279

MSN2 and MSN4 Link Calorie Restriction and TOR to Sirtuin-Mediated Lifespan Extension in Saccharomyces cerevisiae

Medvedik, O., Lamming, D. W., Kim, K. D., & Sinclair, D. A. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050261 · Cited by 275

Effects of intermittent and continuous calorie restriction on body weight and metabolism over 50 wk: a randomized controlled trial

Schübel, R., Nattenmüller, J., Sookthai, D., Nonnenmacher, T., Graf, M. E., Riedl, L., Schlett, C. L., von Stackelberg, O., Johnson, T., Nabers, D., et al. (2018) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqy196 · Cited by 274

Caloric restriction delays age-related methylation drift

Maegawa, S., Lu, Y., Tahara, T., Lee, J. T., Madzo, J., Liang, S., Jelinek, J., Colman, R. J., & Issa, J.-P. J. (2017) · Nature Communications · doi:10.1038/s41467-017-00607-3 · Cited by 270

Lifelong restriction of dietary branched-chain amino acids has sex-specific benefits for frailty and life span in mice

Richardson, N. E., Konon, E. N., Schuster, H. S., Mitchell, A. T., Boyle, C., Rodgers, A. C., Finke, M., Haider, L. R., Yu, D., Flores, V., et al. (2021) · Nature Aging · doi:10.1038/s43587-020-00006-2 · Cited by 267

Calorie restriction in humans inhibits the PI 3 K/AKT pathway and induces a younger transcription profile

Mercken, E. M., Crosby, S. D., Lamming, D. W., JeBailey, L., Krzysik‐Walker, S., Villareal, D. T., Capri, M., Franceschi, C., Zhang, Y., Becker, K., et al. (2013) · Aging Cell · doi:10.1111/acel.12088 · Cited by 261

The effects of short-term fasting on quality of life and tolerance to chemotherapy in patients with breast and ovarian cancer: a randomized cross-over pilot study

Bauersfeld, S. P., Keßler, C. S., Wischnewsky, M. B., Jaensch, A., Steckhan, N., Stange, R., Kunz, B., Brückner, B., Sehouli, J., & Michalsen, A. (2018) · BMC Cancer · doi:10.1186/s12885-018-4353-2 · Cited by 260

Mice under Caloric Restriction Self-Impose a Temporal Restriction of Food Intake as Revealed by an Automated Feeder System

Acosta-Rodríguez, V. A., de Groot, M. H. M., Rijo‐Ferreira, F., Green, C. B., & Takahashi, J. S. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.06.007 · Cited by 252

Activating transcription factor 4-dependent induction of FGF21 during amino acid deprivation

De Sousa-Coelho, A. L., Marrero, P. F., & Haro, D. (2012) · Biochemical Journal · doi:10.1042/bj20111748 · Cited by 246

D-Glucosamine supplementation extends life span of nematodes and of ageing mice

Weimer, S., Priebs, J., Kuhlow, D., Groth, M., Priebe, S., Mansfeld, J., Merry, T. L., Dubuis, S., Laube, B., Pfeiffer, A. F. H., et al. (2014) · Nature Communications · doi:10.1038/ncomms4563 · Cited by 245

Dihydroxyacetone phosphate signals glucose availability to mTORC1

Orozco, J. M., Krawczyk, P. A., Scaria, S. M., Cangelosi, A. L., Chan, S. H., Kunchok, T., Lewis, C. A., & Sabatini, D. M. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0250-5 · Cited by 242

Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island

Apelo, S. I. A., & Lamming, D. W. (2016) · The Journals of Gerontology Series A · doi:10.1093/gerona/glw090 · Cited by 241

Reduced Incidence and Delayed Occurrence of Fatal Neoplastic Diseases in Growth Hormone Receptor/Binding Protein Knockout Mice

Ikeno, Y., Hubbard, G. B., Lee, S., Cortez, L. A., Lew, C. M., Webb, C. R., Berryman, D. E., List, E. O., Kopchick, J. J., & Bartke, A. (2009) · The Journals of Gerontology Series A · doi:10.1093/gerona/glp017 · Cited by 238

SIRT2 induces the checkpoint kinase BubR1 to increase lifespan

North, B. J., Rosenberg, M. A., Jeganathan, K. B., Hafner, A. V., Michan, S., Dai, J., Baker, D. J., Cen, Y., Wu, L. E., Sauve, A. A., et al. (2014) · The EMBO Journal · doi:10.15252/embj.201386907 · Cited by 238

FGF21 Signals Protein Status to the Brain and Adaptively Regulates Food Choice and Metabolism

Hill, C. M., Laeger, T., Dehner, M., Albarado, D. C., Clarke, B., Wanders, D., Burke, S. J., Collier, J. J., Qualls-Creekmore, E., Solon-Biet, S. M., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.05.022 · Cited by 229

HST2 Mediates SIR2 -Independent Life-Span Extension by Calorie Restriction

Lamming, D. W., Latorre‐Esteves, M., Medvedik, O., Wong, S. N., Tsang, F. A., Wang, C., Lin, S.-J., & Sinclair, D. A. (2005) · Science · doi:10.1126/science.1113611 · Cited by 227

The effects of intermittent compared to continuous energy restriction on glycaemic control in type 2 diabetes; a pragmatic pilot trial

Carter, S., Clifton, P. M., & Keogh, J. B. (2016) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2016.10.010 · Cited by 225

The Snell dwarf mutation Pit1dw can increase life span in mice

Flurkey, K., Papaconstantinou, J., & Harrison, D. E. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00339-6 · Cited by 218

Splicing factor 1 modulates dietary restriction and TORC1 pathway longevity in C. elegans

Heintz, C., Doktor, T. K., Lanjuin, A., Escoubas, C. C., Zhang, Y., Weir, H. J. M., Dutta, S., Silva-García, C. G., Bruun, G. H., Morantte, I. G., et al. (2016) · Nature · doi:10.1038/nature20789 · Cited by 217

Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice

Douris, N., Stevanovic, D. M., Fisher, F. M., Cisu, T. I., Chee, M. J., Nguyen, N. L., Zarebidaki, E., Adams, A. C., Kharitonenkov, A., Flier, J. S., et al. (2015) · Endocrinology · doi:10.1210/en.2014-2001 · Cited by 215

Metabolic Responses to Dietary Protein Restriction Require an Increase in FGF21 that Is Delayed by the Absence of GCN2

Laeger, T., Albarado, D. C., Burke, S. J., Trosclair, L., Hedgepeth, J. W., Berthoud, H.-R., Gettys, T. W., Collier, J. J., Münzberg, H., & Morrison, C. D. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.06.044 · Cited by 206

Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21

Lees, E. K., Król, E., Grant, L., Shearer, K., Wyse, C. A., Moncur, E. M., Bykowska, A. S., Mody, N., Gettys, T. W., & Delibegović, M. (2014) · Aging Cell · doi:10.1111/acel.12238 · Cited by 203

Regulators of gut motility revealed by a gnotobiotic model of diet-microbiome interactions related to travel

Dey, N., Wagner, V. E., Blanton, L. V., Cheng, J., Fontana, L., Haque, R., Ahmed, T., & Gordon, J. I. (2015) · Cell · doi:10.1016/j.cell.2015.08.059 · Cited by 195

Phenotypes of Mice Lacking Extracellular Superoxide Dismutase and Copper- and Zinc-containing Superoxide Dismutase

Sentman, M.-L., Granström, M., Jakobson, H., Reaume, A. G., Basu, S., & Marklund, S. L. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m510764200 · Cited by 193

The ribosomal P-stalk couples amino acid starvation to GCN2 activation in mammalian cells

Harding, H. P., Ordóñez, A., Allen, F., Parts, L., Inglis, A. J., Williams, R. L., & Ron, D. (2019) · eLife · doi:10.7554/elife.50149 · Cited by 183

Rapamycin‐mediated mTORC 2 inhibition is determined by the relative expression of FK 506‐binding proteins

Schreiber, K. H., Ortiz, D., Academia, E. C., Anies, A. C., Liao, C., & Kennedy, B. K. (2015) · Aging Cell · doi:10.1111/acel.12313 · Cited by 182

Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system

Arriola Apelo, S. I., Neuman, J. C., Baar, E. L., Syed, F. A., Cummings, N. E., Brar, H. K., Pumper, C. P., Kimple, M. E., & Lamming, D. W. (2016) · Aging Cell · doi:10.1111/acel.12405 · Cited by 182

Sarcopenia of aging: Underlying cellular mechanisms and protection by calorie restriction

Marzetti, E., Lees, H. A., Wohlgemuth, S. E., & Leeuwenburgh, C. (2009) · BioFactors · doi:10.1002/biof.5 · Cited by 181

Cysteine supplementation reverses methionine restriction effects on rat adiposity: Significance of stearoyl-coenzyme A desaturase

Elshorbagy, A. K., Valdivia-Garcia, M., Mattocks, D. A. L., Plummer, J. D., Smith, A. D., Drevon, C. A., Refsum, H., & Perrone, C. E. (2011) · Journal of Lipid Research · doi:10.1194/jlr.m010215 · Cited by 177

A novel rapamycin analog is highly selective for mTORC1 in vivo

Schreiber, K. H., Arriola Apelo, S. I., Yu, D., Brinkman, J. A., Velarde, M. C., Syed, F. A., Liao, C.-Y., Baar, E. L., Carbajal, K. A., Sherman, D. S., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11174-0 · Cited by 177

Long-Term Calorie Restriction Enhances Cellular Quality-Control Processes in Human Skeletal Muscle

Yang, L., Licastro, D., Cava, E., Veronese, N., Spelta, F., Rizza, W., Bertozzi, B., Villareal, D. T., Hotamışlıgil, G. S., Holloszy, J. O., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.042 · Cited by 174

Mice deficient in both Mn superoxide dismutase and glutathione peroxidase-1 have increased oxidative damage and a greater incidence of pathology but no reduction in longevity

Zhang, Y., Ikeno, Y., Qi, W., Chaudhuri, A., Li, Y., Bokov, A., Thorpe, S. R., Baynes, J. W., Epstein, C., Richardson, A., et al. (2009) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glp132 · Cited by 172

Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice

Pak, H. H., Haws, S. A., Green, C. L., Koller, M., Lavarias, M. T., Richardson, N. E., Yang, S. E., Dumas, S. N., Sonsalla, M., Bray, L., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00466-9 · Cited by 171

Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice

Mao, K., Quipildor, G. F., Tabrizian, T., Novaj, A., Guan, F., Walters, R. O., Delahaye, F., Hubbard, G. B., Ikeno, Y., Ejima, K., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04805-5 · Cited by 167

Prior dietary practices and connections to a human gut microbial metacommunity alter responses to diet interventions

Griffin, N. W., Ahern, P. P., Cheng, J., Heath, A. C., Ilkayeva, O., Newgard, C. B., Fontana, L., & Gordon, J. I. (2017) · Cell Host & Microbe · doi:10.1016/j.chom.2016.12.006 · Cited by 164

Dietary Restriction Extends Lifespan through Metabolic Regulation of Innate Immunity

Wu, Z., Isik, M., Moroz, N., Steinbaugh, M. J., Zhang, P., & Blackwell, T. K. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.02.013 · Cited by 163

A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs

Urfer, S. R., Kaeberlein, T. L., Mailheau, S., Bergman, P. J., Creevy, K. E., Promislow, D. E. L., & Kaeberlein, M. (2017) · GeroScience · doi:10.1007/s11357-017-9972-z · Cited by 158

Loss of pregnancy‐associated plasma protein A extends lifespan in mice

Conover, C. A., & Bale, L. K. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00328.x · Cited by 154

Does Reduced IGF-1R Signaling in Igf1r+/− Mice Alter Aging?

Bokov, A. F., Garg, N., Ikeno, Y., Thakur, S., Musi, N., DeFronzo, R. A., Zhang, N., Erickson, R. C., Gelfond, J., Hubbard, G. B., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026891 · Cited by 152

Effects of Intermittent Versus Continuous Energy Intakes on Insulin Sensitivity and Metabolic Risk in Women with Overweight

Hutchison, A. T., Liu, B., Wood, R. E., Vincent, A. D., Thompson, C. H., O’Callaghan, N. J., Wittert, G., & Heilbronn, L. K. (2018) · Obesity · doi:10.1002/oby.22345 · Cited by 152

Differences in circulating gluconeogenic substrates during short-term fasting in men, women, and children

Haymond, M. W., Karl, I. E., Clarke, W. L., Pagliara, A. S., & Santiago, J. V. (1982) · Metabolism · doi:10.1016/0026-0495(82)90024-5 · Cited by 148

Dietary Protein, Metabolism, and Aging

Soultoukis, G. A., & Partridge, L. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014422 · Cited by 148

Mice Fed Rapamycin Have an Increase in Lifespan Associated with Major Changes in the Liver Transcriptome

Fok, W. C., Chen, Y., Bokov, A. F., Zhang, Y., Salmon, A. B., Diaz, V., Javors, M. A., Wood, W. H., Zhang, Y., Becker, K. G., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0083988 · Cited by 146

Cellular senescence and senolytics: the path to the clinic

Chaib, S., Tchkonia, T., & Kirkland, J. L. (2022) · Nature Medicine · doi:10.1038/s41591-022-01923-y · Cited by 1,134

Ageing and rejuvenation of tissue stem cells and their niches

Brunet, A., Goodell, M. A., & Rando, T. A. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00510-w · Cited by 407

Regulators of health and lifespan extension in genetically diverse mice on dietary restriction

Di Francesco, A., Deighan, A. G., Litichevskiy, L., Chen, Z., Luciano, A., Robinson, L., Garland, G., Donato, H., Schott, W., Wright, K. M., et al. (2023) · doi:10.1101/2023.11.28.568901 · Cited by 194

Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice

Pak, H. H., Haws, S. A., Green, C. L., Koller, M., Lavarias, M. T., Richardson, N. E., Yang, S. E., Dumas, S. N., Sonsalla, M., Bray, L., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00466-9 · Cited by 171

Obesity accelerates cardiovascular ageing

Ruperez, C., Madeo, F., de Cabo, R., Kroemer, G., & Abdellatif, M. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf216 · Cited by 73

Calorie-restriction and longevity. End of a dream, at least for primates?

Robert, L. (2013) · European Geriatric Medicine · doi:10.1016/j.eurger.2013.02.005 · Cited by 11

The AMPK-SIRT signaling network regulates glucose tolerance under calorie restriction conditions

Silvestre, M. P., Viollet, B., Caton, P., Leclerc, J., Sakakibara, I., Foretz, M., Holness, M., & Sugden, M. C. (2014) · Life Sciences · doi:10.1016/j.lfs.2014.01.080 · Cited by 54

Why calorie restriction would work for human longevity

Yu, B. P. (2006) · Biogerontology · doi:10.1007/s10522-006-9009-y · Cited by 36

Growth Hormone and IGF-1 Axis in Aging and Longevity

Shimokawa, I. (2017) · Healthy ageing and longevity · doi:10.1007/978-3-319-63001-4_5 · Cited by 8

Programmed longevity, youthspan, and juventology

Longo, V. D. (2018) · Aging Cell · doi:10.1111/acel.12843 · Cited by 32