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Drugs that modulate aging: the promising yet difficult path ahead
Open accessAbstract
Once a backwater in medical sciences, aging research has emerged and now threatens to take the forefront. This dramatic change of stature is driven from 3 major events. First and foremost, the world is rapidly getting old. Never before have we lived in a demographic environment like today, and the trends will continue such that 20% percent of the global population of 9 billion will be over the age of 60 by 2050. Given current trends of sharply increasing chronic disease incidence, economic disaster from the impending silver tsunami may be ahead. A second major driver on the rise is the dramatic progress that aging research has made using invertebrate models such as worms, flies, and yeast. Genetic approaches using these organisms have led to hundreds of aging genes and, perhaps surprisingly, strong evidence of evolutionary conservation among longevity pathways between disparate species, including mammals. Current studies suggest that this conservation may extend to humans. Finally, small molecules such as rapamycin and resveratrol have been identified that slow aging in model organisms, although only rapamycin to date impacts longevity in mice. The potential now exists to delay human aging, whether it is through known classes of small molecules or a plethora of emerging ones. But how can a drug that slows aging become approved and make it to market when aging is not defined as a disease. Here, we discuss the strategies to translate discoveries from aging research into drugs. Will aging research lead to novel therapies toward chronic disease, prevention of disease or be targeted directly at extending lifespan?
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“Evidence amassed in recent years indicates that aging science shows great promise as a method of extending health span (50)(51)(52)(53)(54)(55)(56).”
From Inconvenient Truths About Human Longevity (2019) · cites this paper as [50]
In the citing paper
“A growing body of research has highlighted mTOR inhibitors, i.e., rapamycin and everolimus, as promising treatments for several age-related pathologies, including immunosenescence, prolonging lifespan, especially in all four major animal models of aging: yeast, worms, flies, and mice (204, 205).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [205]
In the citing paper
“A growing body of research has highlighted mTOR inhibitors, i.e., rapamycin and everolimus, as promising treatments for several age-related pathologies, including immunosenescence, prolonging lifespan, especially in all four major animal models of aging: yeast, worms, flies, and mice (204, 205).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [205]
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Citations
Cites
mTOR Signaling in Growth Control and Disease
Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509
Pleiotropy, natural selection, and the evolution of senescence.
Williams, G. C. (1957) · Evolution · doi:10.1111/j.1558-5646.1957.tb02911.x · Cited by 4,279
Therapeutic potential of resveratrol: the in vivo evidence
Baur, J. A., & Sinclair, D. A. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2060 · Cited by 3,958
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
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
A C. elegans mutant that lives twice as long as wild type
Kenyon, C., Chang, J., Gensch, E., Rudner, A., & Tabtiang, R. (1993) · Nature · doi:10.1038/366461a0 · Cited by 3,387
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
Kenyon, C. J. (2010) · Nature · doi:10.1038/nature08980 · Cited by 2,739
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
Kaeberlein, M., McVey, M., & Guarente, L. (1999) · Genes & Development · doi:10.1101/gad.13.19.2570 · Cited by 2,253 · cited 8×
“M AN US CR IP T AC CE PT ED Abbreviations: FDA = Food and Drug Administration; IGF = Insulin-like Growth Factor; SIR2 = Silent Information Regulator Two; IIS = Insulin/IGF Signaling; PKA = Protein Kinase A; mTOR = Mammalian Target Of Rapamycin; TORC1 = Target of Rapamycin Complex 1; TORC2 = Target of Rapamycin Complex…”
BackgroundInfluentialKirkwood, T. B. L. (1977) · Nature · doi:10.1038/270301a0 · Cited by 2,007
Understanding the odd science of aging
Kirkwood, T. B. L. (2005) · Cell · doi:10.1016/j.cell.2005.01.027 · Cited by 1,984
Pleiotropy, natural selection, and the evolution of senescence
Williams, G. C. (1957) · Evolution · doi:10.2307/2406060 · Cited by 1,912
The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation
Mendoza, M. C., Er, E. E., & Blenis, J. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2011.03.006 · Cited by 1,817
Lin, S.-J., Defossez, P.-A., & Guarente, L. (2000) · Science · doi:10.1126/science.289.5487.2126 · Cited by 1,775
Kirkwood, T. B. L., & Austad, S. N. (2000) · Nature · doi:10.1038/35041682 · Cited by 1,774
Vézina, C., KUDELSKI, A., & Sehgal, S. N. (1975) · The Journal of Antibiotics · doi:10.7164/antibiotics.28.721 · Cited by 1,691
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
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
Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
Tissenbaum, H. A., & Guarente, L. (2001) · Nature · doi:10.1038/35065638 · Cited by 1,603
Extrachromosomal rDNA circles—a cause of aging in yeast
Sinclair, D. A., & Guarente, L. (1997) · Cell · doi:10.1016/s0092-8674(00)80493-6 · Cited by 1,500
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
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
Longevity, senescence and the genome
(1995) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(95)90026-8 · Cited by 1,403
Sir2 mediates longevity in the fly through a pathway related to calorie restriction
Rogina, B., & Helfand, S. L. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404184101 · Cited by 1,361
Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway
Kapahi, P., Zid, B. M., Harper, T., Koslover, D., Sapin, V., & Benzer, S. (2004) · Current Biology · doi:10.1016/j.cub.2004.03.059 · Cited by 1,293
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
Self-citationLoss of a-Type Lamin Expression Compromises Nuclear Envelope Integrity Leading to Muscular Dystrophy
Sullivan, T. L., Escalante‐Alcalde, D., Bhatt, H., Anver, M. R., Bhat, N. R., Nagashima, K., Stewart, C. L., & Burke, B. E. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.5.913 · Cited by 1,224
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
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
Rates of Behavior and Aging Specified by Mitochondrial Function During Development
Dillin, A., Hsu, A.-L., Arantes-Oliveira, N., Lehrer-Graiwer, J., Hsin, H., Fraser, A. G., Kamath, R. S., Ahringer, J., & Kenyon, C. (2002) · Science · doi:10.1126/science.1077780 · Cited by 1,121
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 · cited 2×
“M AN US CR IP T AC CE PT ED Abbreviations: FDA = Food and Drug Administration; IGF = Insulin-like Growth Factor; SIR2 = Silent Information Regulator Two; IIS = Insulin/IGF Signaling; PKA = Protein Kinase A; mTOR = Mammalian Target Of Rapamycin; TORC1 = Target of Rapamycin Complex 1; TORC2 = Target of Rapamycin Complex…”
BackgroundDwarf 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
Mechanism of Human SIRT1 Activation by Resveratrol
Borra, M. T., Smith, B. C., & Denu, J. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501250200 · Cited by 1,065
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
Influence of TOR kinase on lifespan in C. elegans
Vellai, T., Takacs-Vellai, K., Zhang, Y., Kovacs, A. L., Orosz, L., & Müller, F. (2003) · Nature · doi:10.1038/426620a · Cited by 1,057
Spilman, P., Podlutskaya, N., Hart, M. J., Debnath, J., Gorostiza, O., Bredesen, D., Richardson, A., Strong, R., & Galvan, V. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009979 · Cited by 1,033
FOXO3A genotype is strongly associated with human longevity
Willcox, B. J., Donlon, T. A., He, Q., Chen, R., Grove, J. S., Yano, K., Masaki, K. H., Willcox, D. C., Rodriguez, B., & Curb, J. D. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801030105 · Cited by 983
Extension of Chronological Life Span in Yeast by Decreased TOR Pathway Signaling
Powers, R. W., Kaeberlein, M., Caldwell, S. D., Kennedy, B. K., & Fields, S. (2006) · Genes & Development · doi:10.1101/gad.1381406 · Cited by 982
Self-citationA systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity
Lee, S. S., Lee, R. Y. N., Fraser, A. G., Kamath, R. S., Ahringer, J., & Ruvkun, G. (2003) · Nature Genetics · doi:10.1038/ng1056 · Cited by 969
Target of Rapamycin (TOR) in Nutrient Signaling and Growth Control
Loewith, R., & Hall, M. N. (2011) · Genetics · doi:10.1534/genetics.111.133363 · Cited by 927
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
Morris, J. Z., Tissenbaum, H. A., & Ruvkun, G. (1996) · Nature · doi:10.1038/382536a0 · Cited by 891
Bolster, D. R., Crozier, S. J., Kimball, S. R., & Jefferson, L. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200171200 · Cited by 851
Kirkwood, T. B. L. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00419-5 · Cited by 801
Life Span of Individual Yeast Cells
Mortimer, R., & Johnston, J. R. (1959) · Nature · doi:10.1038/1831751a0 · Cited by 762
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
Substrate-specific activation of sirtuins by resveratrol
Kaeberlein, M., McDonagh, T., Heltweg, B., Hixon, J., Westman, E. A., Caldwell, S. D., Napper, A., Curtis, R., DiStefano, P. S., Fields, S., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500655200 · Cited by 745
Self-citationFunctionally significant insulin-like growth factor I receptor mutations in centenarians
Suh, Y., Atzmon, G., Cho, M.-O., Hwang, D., Liu, B., Leahy, D. J., Barzilai, N., & Cohen, P. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705467105 · Cited by 703
mTOR Regulation and Therapeutic Rejuvenation of Aging Hematopoietic Stem Cells
Chen, C., Liu, Y., Liu, Y., & Zheng, P. (2009) · Science Signaling · doi:10.1126/scisignal.2000559 · Cited by 680
Histone H4 lysine 16 acetylation regulates cellular lifespan
Dang, W., Steffen, K. K., Perry, R., Dorsey, J. A., Johnson, F. B., Shilatifard, A., Kaeberlein, M., Kennedy, B. K., & Berger, S. L. (2009) · Nature · doi:10.1038/nature08085 · Cited by 667
Self-citationmTORC1 controls fasting-induced ketogenesis and its modulation by ageing
Sengupta, S., Peterson, T. R., Laplante, M., Oh, S., & Sabatini, D. M. (2010) · Nature · doi:10.1038/nature09584 · Cited by 646
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
Wilkinson, J. E., Burmeister, L., Brooks, S. V., Chan, C., Friedline, S., Harrison, D. E., Hejtmancik, J. F., Nadon, N., Strong, R., Wood, L. K., et al. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00832.x · Cited by 619
Jia, K., Chen, D., & Riddle, D. L. (2004) · Development · doi:10.1242/dev.01255 · Cited by 615
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
Replicative and chronological aging in Saccharomyces cerevisiae
Longo, V. D., Shadel, G. S., Kaeberlein, M., & Kennedy, B. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.06.002 · Cited by 595
Self-citationSarkar, S., Ravikumar, B., Floto, R. A., & Rubinsztein, D. C. (2009) · Cell Death & Differentiation · doi:10.1038/cdd.2008.110 · Cited by 578
Association of FOXO3A variation with human longevity confirmed in German centenarians
Flachsbart, F., Caliebe, A., Kleindorp, R., Blanché, H., von Eller-Eberstein, H., Nikolaus, S., Schreiber, S., & Nebel, A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809594106 · Cited by 572
Evidence for a common mechanism of SIRT1 regulation by allosteric activators
Hubbard, B. P., Gomes, A. P., Dai, H., Li, J., Case, A. W., Considine, T., Riera, T. V., Lee, J. E., E, S. Y., Lamming, D. W., et al. (2013) · Science · doi:10.1126/science.1231097 · Cited by 561
Hansen, M., Hsu, A., Dillin, A. G., & Kenyon, C. J. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0010017 · Cited by 543
Superoxide Dismutase Activity Is Essential for Stationary Phase Survival in Saccharomyces cerevisiae
Longo, V. D., Gralla, E. B., & Valentine, J. S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.21.12275 · Cited by 531
Rapalogs and mTOR inhibitors as anti-aging therapeutics
Lamming, D. W., Ye, L., Sabatini, D. M., & Baur, J. A. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64099 · Cited by 531
A systematic RNAi screen for longevity genes in C. elegansPreprint
Hamilton, B., Dong, Y., Shindo, M., Liu, W., Odell, I., Ruvkun, G., & Lee, S. S. (2005) · Genes & Development · doi:10.1101/gad.1308205 · Cited by 513
Investigating Metformin for Cancer Prevention and Treatment: The End of the Beginning
Pollak, M. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0263 · Cited by 512
Mutation in the silencing gene S/R4 can delay aging in S. cerevisiae
Kennedy, B. K., Austriaco, N. P. G., Zhang, J., & Guarente, L. (1995) · Cell · doi:10.1016/0092-8674(95)90499-9 · Cited by 492
Self-citationLifespan Regulation by Evolutionarily Conserved Genes Essential for Viability
Curran, S. P., & Ruvkun, G. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030056 · Cited by 485
Rapamycin Protects against Neuron Death inIn VitroandIn VivoModels of Parkinson's Disease
Malagelada, C., Jin, Z. H., Jackson-Lewis, V. R., Przedborski, S., & Greene, L. A. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3944-09.2010 · Cited by 465
Klass, M. R. (1983) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(83)90082-9 · Cited by 449
Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C–deficient mice
Nikolova-Krstevski, V., Leimena, C., McMahon, A. C., Tan, J. C., Chandar, S., Jogia, D., Kesteven, S. H., Michalicek, J., Otway, R., Verheyen, F., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19448 · Cited by 436
Lessons on longevity from budding yeast
Kaeberlein, M. R. (2010) · Nature · doi:10.1038/nature08981 · Cited by 427
Finch, C. E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909606106 · Cited by 417
When Lamins Go Bad: Nuclear Structure and Disease
Schreiber, K. H., & Kennedy, B. K. (2013) · Cell · doi:10.1016/j.cell.2013.02.015 · Cited by 407
Self-citationGENETICS OF LIFE HISTORY IN DROSOPHILA MELANOGASTER. II. EXPLORATORY SELECTION EXPERIMENTS
Rose, M. R., & Charlesworth, B. (1981) · Genetics · doi:10.1093/genetics/97.1.187 · Cited by 407
Are sirtuins viable targets for improving healthspan and lifespan?
Baur, J. A., Ungvari, Z. I., Minor, R. K., Couteur, D. G. L., & de Cabo, R. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3738 · Cited by 393
AMP-Activated Protein Kinase: A Target for Drugs both Ancient and Modern
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.08.019 · Cited by 385
Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C–deficient mice
Nikolova, V., Leimena, C., McMahon, A. C., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200419448 · Cited by 370
Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity
Pawlikowska, L., Hu, D., Huntsman, S., Sung, A., Chu, C., Chen, J., Joyner, A. H., Schork, N. J., Hsueh, W., Reiner, A. P., et al. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00493.x · Cited by 358
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
Ramos, F. J., Chen, S. C., Garelick, M. G., Dai, D.-F., Liao, C.-Y., Schreiber, K. H., MacKay, V. L., An, E. H., Strong, R., Ladiges, W. C., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003802 · Cited by 349
Self-citationStanfel, M. N., Shamieh, L. S., Kaeberlein, M. R., & Kennedy, B. K. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.06.007 · Cited by 347
Self-citationGenetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations
Li, Y., Wang, W., Cao, H., Lu, J., Wu, C., Hu, F., Guo, J., Zhao, L., Yang, F., Zhang, Y.-X., et al. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp459 · Cited by 323
Ramsey, K. M., Mills, K. F., Satoh, A., & Imai, S. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2007.00355.x · Cited by 321
Late-life rapamycin treatment reverses age-related heart dysfunction
Flynn, J. M., O’Leary, M. N., Zambataro, C. A., Academia, E. C., Presley, M. P., Garrett, B., Zykovich, A., Mooney, S. D., Strong, R., Rosen, C. J., et al. (2013) · Aging Cell · doi:10.1111/acel.12109 · Cited by 314
Self-citationAssociation of the FOXO3A Locus with Extreme Longevity in a Southern Italian Centenarian Study
Anselmi, C. V., Malovini, A. L., Roncarati, R., Novelli, V., Villa, F., Condorelli, G., Bellazzi, R., & Puca, A. A. (2009) · Rejuvenation Research · doi:10.1089/rej.2008.0827 · Cited by 310
Rapamycin Extends Life and Health in C57BL/6 Mice
Zhang, Y., Bokov, A. F., Gelfond, J., Soto, V., Ikeno, Y., Hubbard, G. B., Diaz, V., Sloane, L. B., Maslin, K., Treaster, S. B., et al. (2013) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt056 · Cited by 283
Longevity Regulation by Drosophila Rpd3 Deacetylase and Caloric Restriction
Rogina, B., Helfand, S. L., & Frankel, S. A. (2002) · Science · doi:10.1126/science.1078986 · Cited by 276
Selection for life span in Drosophila melanogaster
Luckinbill, L. S., & Clare, M. J. (1985) · Heredity · doi:10.1038/hdy.1985.66 · Cited by 242
Friedman, D. B., & Johnson, T. E. (1988) · Journal of Gerontology · doi:10.1093/geronj/43.4.b102 · Cited by 240 · cited 2×
“It was clear from these studies that extending lifespan was possible through methods such as mutagenesis and screening (10, 12, 20), or through selection, for instance, by isolating flies that maintain late”
BackgroundMethodThe sirtuin family’s role in aging and age-associated pathologies
Hall, J. A., Dominy, J. E., Lee, Y., & Puigserver, P. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64094 · Cited by 240
Nuclear lamin functions and disease
Butin‐Israeli, V., Adam, S. A., Goldman, A. E., & Goldman, R. D. (2012) · Trends in Genetics · doi:10.1016/j.tig.2012.06.001 · Cited by 239
Gallinetti, J., Harputlugil, E., & Mitchell, J. R. (2012) · Biochemical Journal · doi:10.1042/bj20121098 · Cited by 234
Temsirolimus Activates Autophagy and Ameliorates Cardiomyopathy Caused by Lamin A/C Gene Mutation
Choi, J. C., Muchir, A., Wu, W., Iwata, S., Homma, S., Morrow, J., & Worman, H. J. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003875 · Cited by 228
Strong, R., Miller, R. A., Astle, C. M., Baur, J. A., de Cabo, R., Fernandez, E., Guo, W., Javors, M., Kirkland, J. L., Nelson, J. F., et al. (2013) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/gls070 · Cited by 212
Calorie restriction: Decelerating mTOR-driven aging from cells to organisms (including humans)
Blagosklonny, M. V. (2010) · Cell Cycle · doi:10.4161/cc.9.4.10766 · Cited by 211
Quantitative evidence for conserved longevity pathways between divergent eukaryotic speciesPreprint
Smith, E. D., Tsuchiya, M., Fox, L. A., Dang, N., Hu, D., Kerr, E. O., Johnston, E. D., Tchao, B. N., Pak, D. N., Welton, K. L., et al. (2008) · Genome Research · doi:10.1101/gr.074724.107 · Cited by 200
Self-citationDivergent roles of RAS1 and RAS2 in yeast longevity
Sun, J., Kale, S. P., Childress, A. M., Pinswasdi, C., & Jazwinski, S. M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32357-8 · Cited by 193
Meissner, B., Boll, M., Daniel, H., & Baumeister, R. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403415200 · Cited by 171
Soerensen, M., Dato, S., Christensen, K., McGue, M. K., Stevnsner, T., Bohr, V. A., & Christiansen, L. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00627.x · Cited by 165
Metformin for aging and cancer prevention
Anisimov, V. N. (2010) · Aging · doi:10.18632/aging.100230 · Cited by 142
Longevity determined by developmental arrest genes in Caenorhabditis elegans
Chen, D., Pan, K. Z., Palter, J. E., & Kapahi, P. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00305.x · Cited by 138
The evolutionary theories of aging revisited - a mini-review
Ljubuncic, P., & Reznick, A. Z. (2009) · Gerontology · doi:10.1159/000200772 · Cited by 133
Kim, Y.-S., & Sun, H. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00302.x · Cited by 122
dSir2 in the Adult Fat Body, but Not in Muscles, Regulates Life Span in a Diet-Dependent Manner
Banerjee, K. K., Ayyub, C., Syed, Z. A., Mandot, V., Prasad, N. G., & Kolthur‐Seetharam, U. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.11.013 · Cited by 117
Rizki, G., Iwata, T., Li, J., Riedel, C. G., Picard, C. L., Jan, M., Murphy, C. T., & Lee, S. S. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002235 · Cited by 116
Kwan, E. X., Foss, E. J., Tsuchiyama, S. K., Alvino, G. M., Kruglyak, L., Kaeberlein, M. R., Raghuraman, M. K., Brewer, B. J., Kennedy, B. K., & Bedalov, A. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003329 · Cited by 108
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Enns, L. C., Morton, J., Treuting, P. R., Emond, M. J., Wolf, N. S., McKnight, G. S., Rabinovitch, P. S., & Ladiges, W. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005963 · Cited by 96
Diverse aging rates in metazoans: targets for functional genomics
Austad, S. N. (2004) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.09.022 · Cited by 90
Yu, X., & Li, G. (2012) · Experimental Gerontology · doi:10.1016/j.exger.2012.08.009 · Cited by 78
Dietary restriction: standing up for sirtuins
Baur, J. A., Chen, D., Chini, E. N., Chua, K., Cohen, H. Y., Cabo, R. D., Deng, C., Dimmeler, S., Gius, D., Guarente, L. P., et al. (2010) · Science · doi:10.1126/science.329.5995.1012 · Cited by 76
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Hector, K. L., Lagisz, M., & Nakagawa, S. (2012) · Biology Letters · doi:10.1098/rsbl.2012.0316 · Cited by 65
The genetics of ageing: insight from genome‐wide approaches in invertebrate model organisms
Kennedy, B. K. (2008) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2007.01903.x · Cited by 64
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Olivieri, F., Mazzanti, I., M. Abbatecola, A., Recchioni, R., Marcheselli, F., D. Procopio, A., & Antonicelli, R. (2012) · Current Vascular Pharmacology · doi:10.2174/157016112799305076 · Cited by 51 · cited 1×
“Statins may also prevent cellular senescence, possibly through reducing levels of reactive oxygen species and/or stabilizing telomere structures (111).”
BackgroundGenade, T., & Lang, D. M. (2012) · Experimental Gerontology · doi:10.1016/j.exger.2012.11.013 · Cited by 41
Effects of age and gender on Sirt 1 mRNA expressions in the hypothalamus of the mouse
Lafontaine-Lacasse, M., Richard, D., & Picard, F. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.01.008 · Cited by 39
Zhao, L., Yang, F., Xu, K., Cao, H., Zheng, G.-Y., Zhang, Y., Li, J., Cui, H., Chen, X., Zhu, Z., et al. (2012) · Aging Cell · doi:10.1111/acel.12011 · Cited by 37
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Ovalle, F. (2011) · Clinical Therapeutics · doi:10.1016/j.clinthera.2011.04.006 · Cited by 28
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Touzot, M., Soulillou, J., & Dantal, J. (2012) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0b013e32835a4be2 · Cited by 28
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Clark, A. M., & Gould, A. B. (1970) · Experimental Gerontology · doi:10.1016/0531-5565(70)90004-5 · Cited by 27
Cognitive intervention response is related to habitual physical activity in older adults.
Schiattarella, G. G., Perrino, C., Magliulo, F., Ilardi, F., Serino, F., Trimarco, V., Izzo, R., Amato, B., Terranova, C., Cardin, F., et al. (2012) · PubMed · doi:10.3275/7569 · Cited by 26
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Kaeberlein, M. R. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.06.004 · Cited by 22
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Kolovou, G. D., Kolovou, V., Vasiliadis, I. K., Wierzbicki, A. S., & Mikhailidis, D. P. (2011) · Current Opinion in Cardiology · doi:10.1097/hco.0b013e32834659d4 · Cited by 12
Gendron, C. M., Minois, N., Longo, V. D., Pletcher, S. D., & Vaupel, J. W. (2003) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2003.08.003 · Cited by 11
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Schiattarella, G. G., Perrino, C., Magliulo, F., Ilardi, F., Serino, F., Trimarco, V., Izzo, R., Amato, B., Terranova, C., Cardin, F., et al. (2012) · MDC Repository (Max-Delbrueck-Center for Molecular Medicine) · Cited by 8
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“Many of the interventions that extend lifespan in model organisms have the effect of reducing mTORC1 signaling (Johnson et al. , 2013; Kennedy & Pennypacker, 2014).”
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Metadata
- Authors
- Kennedy, B. K., & Pennypacker, J. K.
- Affiliations
- Buck Institute for Research on Aging (US)
- Corresponding author
- Kennedy, Brian K.
- ORCID
- Kennedy, Brian K.
- Venue
- Translational research
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 163
- Issue
- 5
- Pages
- 456-465
- ISSN
- 1878-1810 (ISSN-L)
- 1931-5244
- PMC
- PMC4004650
- OpenAlex
- W2111463058
- Cited by
- 127
- References
- 123
- Citations by year
- 2026: 1 · 2025: 10 · 2024: 5 · 2023: 8 · 2022: 10 · 2021: 8 · 2020: 14 · 2019: 15 · 2018: 10 · 2017: 8 · 2016: 11 · 2015: 12 · 2014: 13
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Translational research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG033373)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Keywords
- aging, anti-aging drugs, longevity, aging research, rapamycin, resveratrol, aging-related genes, small molecules, drug development, lifespan extension, chronic disease, invertebrate models
- MeSH terms
- Aging, Animals, Gene Expression Regulation, Humans, United States, Translational Research, Biomedical
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