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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mTOR inhibitors rapamycin and everolimus prolong lifespan in yeast, worms, flies, and mice.
“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]
mTOR inhibitors rapamycin and everolimus are promising treatments for several age-related pathologies, including immunosenescence.
“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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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 · see citing works
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 · see citing works
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 · 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
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 · see citing works
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 · 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
Kenyon, C. J. (2010) · Nature · doi:10.1038/nature08980 · Cited by 2,739 · see citing works
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 2,645 · see citing works
Kaeberlein, M., McVey, M., & Guarente, L. (1999) · Genes & Development · doi:10.1101/gad.13.19.2570 · Cited by 2,253 · cited 8× · see citing works
“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 · see citing works
Understanding the odd science of aging
Kirkwood, T. B. L. (2005) · Cell · doi:10.1016/j.cell.2005.01.027 · Cited by 1,984 · see citing works
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 1,918 · see citing works
Pleiotropy, natural selection, and the evolution of senescence
Williams, G. C. (1957) · Evolution · doi:10.2307/2406060 · Cited by 1,912 · see citing works
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 · see citing works
Lin, S.-J., Defossez, P.-A., & Guarente, L. (2000) · Science · doi:10.1126/science.289.5487.2126 · Cited by 1,775 · see citing works
Kirkwood, T. B. L., & Austad, S. N. (2000) · Nature · doi:10.1038/35041682 · Cited by 1,774 · see citing works
Vézina, C., KUDELSKI, A., & Sehgal, S. N. (1975) · The Journal of Antibiotics · doi:10.7164/antibiotics.28.721 · Cited by 1,691 · see citing works
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 · see citing works
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 · see citing works
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 · 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
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 · see citing works
Longevity, senescence and the genome
(1995) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(95)90026-8 · Cited by 1,403 · see citing works
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 · see citing works
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 1,348 · see citing works
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 · see citing works
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 · see citing works
Self-citationRapamycin-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 · see citing works
Loss 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. K., Nagashima, K., Stewart, C. L., & Burke, B. E. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.5.913 · Cited by 1,197 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 900 · 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
Morris, J. Z., Tissenbaum, H. A., & Ruvkun, G. (1996) · Nature · doi:10.1038/382536a0 · Cited by 891 · see citing works
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 · see citing works
Kirkwood, T. B. L. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00419-5 · Cited by 801 · see citing works
Life Span of Individual Yeast Cells
Mortimer, R., & Johnston, J. R. (1959) · Nature · doi:10.1038/1831751a0 · Cited by 762 · see citing works
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 · see citing works
Self-citationSatoh, 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 734 · see citing works
Jia, K., Chen, D., & Riddle, D. L. (2004) · Development · doi:10.1242/dev.01255 · Cited by 706 · see citing works
Functionally 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 · see citing works
Wilkinson, J. E., Burmeister, L., Brooks, S. V., Chan, C., Friedline, S., Harrison, D. E., Hejtmancik, J. F., Nadon, N. L., Strong, R., Wood, L. K., et al. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00832.x · Cited by 684 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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., Yen, E. S., Lamming, D. W., et al. (2013) · Science · doi:10.1126/science.1231097 · Cited by 618 · see citing works
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 · see citing works
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 · see citing works
Self-citationSarkar, S., Ravikumar, B., Floto, R. A., & Rubinsztein, D. C. (2009) · Cell Death & Differentiation · doi:10.1038/cdd.2008.110 · Cited by 578 · see citing works
Association of <i>FOXO3A</i> 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 · see citing works
Hansen, M., Hsu, A., Dillin, A. G., & Kenyon, C. J. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0010017 · Cited by 533 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 505 · see citing works
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 499 · see citing works
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 479 · see citing works
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 458 · see citing works
Klass, M. R. (1983) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(83)90082-9 · Cited by 449 · see citing works
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 428 · see citing works
Lessons on longevity from budding yeast
Kaeberlein, M. R. (2010) · Nature · doi:10.1038/nature08981 · Cited by 418 · see citing works
GENETICS 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 415 · see citing works
Finch, C. E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909606106 · Cited by 407 · see citing works
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 389 · see citing works
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 384 · see citing works
Self-citationAMP-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 373 · see citing works
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 · see citing works
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 · see citing works
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 352 · see citing works
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 · see citing works
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 339 · see citing works
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 · see citing works
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 · see citing works
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 309 · see citing works
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 298 · see citing works
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 · see citing works
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 276 · see citing works
Selection for life span in Drosophila melanogaster
Luckinbill, L. S., & Clare, M. J. (1985) · Heredity · doi:10.1038/hdy.1985.66 · Cited by 242 · see citing works
Friedman, D. B., & Johnson, T. E. (1988) · Journal of Gerontology · doi:10.1093/geronj/43.4.b102 · Cited by 240 · cited 2× · see citing works
“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 235 · see citing works
Strong, R., Miller, R. A., Astle, C. M., Baur, J. A., de Cabo, R., Fernandez, E., Guo, W., Javors, M. A., Kirkland, J. L., Nelson, J. F., et al. (2012) · The Journals of Gerontology Series A · doi:10.1093/gerona/gls070 · Cited by 232 · see citing works
Gallinetti, J., Harputlugil, E., & Mitchell, J. R. (2012) · Biochemical Journal · doi:10.1042/bj20121098 · Cited by 231 · see citing works
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 229 · see citing works
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 217 · see citing works
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 · see citing works
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 198 · see citing works
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 · see citing works
Meissner, B., Boll, M., Daniel, H., & Baumeister, R. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403415200 · Cited by 171 · see citing works
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 · see citing works
Metformin for aging and cancer prevention
Anisimov, V. N. (2010) · Aging · doi:10.18632/aging.100230 · Cited by 140 · see citing works
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 · see citing works
The evolutionary theories of aging revisited - a mini-review
Ljubuncic, P., & Reznick, A. Z. (2009) · Gerontology · doi:10.1159/000200772 · Cited by 133 · see citing works
Kim, Y.-S., & Sun, H. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00302.x · Cited by 120 · see citing works
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 · see citing works
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 113 · see citing works
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 · see citing works
Self-citationDisruption of Protein Kinase A in Mice Enhances Healthy Aging
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 · see citing works
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 · see citing works
Yu, X., & Li, G. (2012) · Experimental Gerontology · doi:10.1016/j.exger.2012.08.009 · Cited by 78 · see citing works
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 · see citing works
The effect of resveratrol on longevity across species: a meta-analysis
Hector, K. L., Lagisz, M., & Nakagawa, S. (2012) · Biology Letters · doi:10.1098/rsbl.2012.0316 · Cited by 65 · see citing works
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 63 · see citing works
Self-citationTelomere/telomerase system: a new target of statins pleiotropic effect?
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× · see citing works
“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 40 · see citing works
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 38 · see citing works
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 · see citing works
Self-citationMechanistic target of rapamycin inhibitors in solid organ transplantation
Touzot, M., Soulillou, J., & Dantal, J. (2012) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0b013e32835a4be2 · Cited by 30 · see citing works
Cardiovascular Implications of Antihyperglycemic Therapies for Type 2 Diabetes
Ovalle, F. (2011) · Clinical Therapeutics · doi:10.1016/j.clinthera.2011.04.006 · Cited by 27 · see citing works
Genetic control of adult life span in Drosophila melanogaster
Clark, A. M., & Gould, A. B. (1970) · Experimental Gerontology · doi:10.1016/0531-5565(70)90004-5 · Cited by 27 · see citing works
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 · see citing works
The Ongoing Saga of Sirtuins and Aging
Kaeberlein, M. R. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.06.004 · Cited by 22 · see citing works
Ideal lipid profile and genes for an extended life span
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 · see citing works
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 · see citing works
Statins and the elderly: recent evidence and current indications
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 · see citing works
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Geroscience: Linking Aging to Chronic Disease
Kennedy, B. K., Berger, S. L., Brunet, A., Campisi, J., Cuervo, A. M., Epel, E. S., Franceschi, C., Lithgow, G. J., Morimoto, R. I., Pessin, J. E., et al. (2014) · Cell · doi:10.1016/j.cell.2014.10.039 · Cited by 2,764 · see citing works
Self-citationAiello, A., Farzaneh, F., Candore, G., Caruso, C., Davinelli, S., Gambino, C. M., Ligotti, M. E., Zareian, N., & Accardi, G. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02247 · Cited by 693 · see citing works
Interventions to slow aging in humans: are we ready?
Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., Curiel, T. J., Cabo, R., Franceschi, C., Gems, D., et al. (2015) · Aging Cell · doi:10.1111/acel.12338 · Cited by 592 · see citing works
“Many of the interventions that extend lifespan in model organisms have the effect of reducing mTORC1 signaling (Johnson et al. , 2013; Kennedy & Pennypacker, 2014).”
Self-citationEssential role for autophagy in life span extension
Madeo, F., Zimmermann, A., Maiuri, M. C., & Kroemer, G. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73946 · Cited by 464 · see citing works
Age-Related Change in Mobility: Perspectives From Life Course Epidemiology and Geroscience.
Ferrucci, L., Cooper, R., Shardell, M., Simonsick, E., Schrack, J., & Kuh, D. (2016) · The journals of gerontology. Series A, Biological sciences and medical sciences · doi:10.1093/gerona/glw043 · Cited by 386 · see citing works
Sirtuins: guardians of mammalian healthspan
Giblin, W., Skinner, M. E., & Lombard, D. B. (2014) · Trends in Genetics · doi:10.1016/j.tig.2014.04.007 · Cited by 280 · see citing works
Medical research: Treat ageing
Fontana, L., Kennedy, B. K., Longo, V. D., Seals, D. R., & Melov, S. (2014) · Nature · doi:10.1038/511405a · Cited by 266 · see citing works
Self-citationJin, K. (2014) · Aging and Disease · doi:10.14336/ad.2014.1210 · Cited by 224 · see citing works
The Business of Anti-Aging Science
de Magalhães, J. P., Stevens, M., & Thornton, D. (2017) · Trends in biotechnology · doi:10.1016/j.tibtech.2017.07.004 · Cited by 167 · see citing works
Anti-aging pharmacology: Promises and pitfalls
Vaiserman, A. M., Lushchak, O. V., & Koliada, A. K. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.08.004 · Cited by 144 · see citing works
Does Longer Lifespan Mean Longer Healthspan?
Hansen, M., & Kennedy, B. K. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.05.002 · Cited by 130 · see citing works
Self-citationAntiaging agents: safe interventions to slow aging and healthy life span extension
Liu, J. (2022) · Natural Products and Bioprospecting · doi:10.1007/s13659-022-00339-y · Cited by 107 · see citing works
He, C. Z., Tsuchiyama, S. K., Nguyen, Q. T. T., Proshkina, E., Terrill, S. R., Sahibzada, S., Patel, B., Faulkner, A. R., Shaposhnikov, M. V., Tian, R., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004860 · Cited by 97 · see citing works
Self-citationThe yeast replicative aging model
He, C. Z., Zhou, C., & Kennedy, B. K. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.02.023 · Cited by 91 · see citing works
Self-citationDAF-16 target identification in C. elegans: past, present and future
Tullet, J. M. A. (2014) · Biogerontology · doi:10.1007/s10522-014-9527-y · Cited by 87 · see citing works
Demidenko, O., Barardo, D., Budovskii, V., Finnemore, R., Palmer, F. R., Kennedy, B. K., & Budovskaya, Y. V. (2021) · Aging · doi:10.18632/aging.203736 · Cited by 86 · see citing works
Self-citationRosoff, D. B., Mavromatis, L. A., Bell, A. S., Wagner, J., Jung, J., Marioni, R. E., Smith, G. D., Horvath, S., & Lohoff, F. W. (2023) · Nature Aging · doi:10.1038/s43587-023-00455-5 · Cited by 83 · see citing works
Popovich, I. G., Anisimov, V. N., Zabezhinski, M. A., Semenchenko, A. V., Тындык, М. Л., Yurova, M. N., & Blagosklonny, M. V. (2014) · Cancer Biology & Therapy · doi:10.4161/cbt.28164 · Cited by 79 · see citing works
Translating the Science of Aging into Therapeutic Interventions
Kirkland, J. L. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a025908 · Cited by 78 · see citing works
Vaiserman, A. M., & Lushchak, O. V. (2017) · Journal of Translational Medicine · doi:10.1186/s12967-017-1259-8 · Cited by 71 · see citing works
Aging and Chronic Liver Disease
Maeso‐Díaz, R., & Gracia‐Sancho, J. (2020) · Seminars in Liver Disease · doi:10.1055/s-0040-1715446 · Cited by 70 · see citing works
Inconvenient Truths About Human Longevity
Olshansky, S. J., & Carnes, B. A. (2019) · The Journals of Gerontology Series A · doi:10.1093/gerona/glz098 · Cited by 67 · see citing works
Hill, B. G., Shiva, S., Ballinger, S. W., Zhang, J., & Darley-Usmar, V. M. (2019) · Biological Chemistry · doi:10.1515/hsz-2019-0268 · Cited by 65 · see citing works
Zhavoronkov, A. A., Buzdin, A. A., Garazha, A., Borisov, N., & Moskalev, A. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00049 · Cited by 56 · see citing works
Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer
Al‐Bari, M. A. A., Ito, Y., Ahmed, S. B. M., Radwan, N., Ahmed, H. S., & Eid, N. A. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189807 · Cited by 55 · see citing works
Metformin alleviates neurocognitive impairment in aging via activation of AMPK/BDNF/PI3K pathway
Ameen, O., Samaka, R. M., & Abo-Elsoud, R. A. A. (2022) · Scientific Reports · doi:10.1038/s41598-022-20945-7 · Cited by 55 · see citing works
Protective effect of atorvastatin on d-galactose-induced aging model in mice
Kaviani, E., Rahmani, M. R., Kaeidi, A., Shamsizadeh, A., Allahtavakoli, M., Mozafari, N., & Fatemi, I. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.07.029 · Cited by 55 · see citing works
Does eating less make you live longer and better? An update on calorie restriction
Picca, A., Pesce, V., & Lezza, A. M. S. (2017) · Clinical Interventions in Aging · doi:10.2147/cia.s126458 · Cited by 54 · see citing works
Ward, D. D., Wallace, L. M. K., & Rockwood, K. J. (2020) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2020-324081 · Cited by 53 · see citing works
Bytyçi, I., & Henein, M. Y. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10122670 · Cited by 52 · see citing works
Protective effect of metformin on D-galactose-induced aging model in mice.
Fatemi, I., Khaluoi, A., Kaeidi, A., Shamsizadeh, A., Heydari, S., & Allahtavakoli, M. (2018) · PubMed Central · doi:10.22038/ijbms.2017.24331.6071 · Cited by 49 · see citing works
Protective effect of walnut on d ‐galactose‐induced aging mouse model
Liu, J., Chen, D., Wang, Z., Chen, C., Ning, D., & Zhao, S. (2019) · Food Science & Nutrition · doi:10.1002/fsn3.907 · Cited by 46 · see citing works
Yao, Y., Tsuchiyama, S. K., Yang, C., Bulteau, A., He, C. Z., Robison, B., Tsuchiya, M., Miller, D. M., Briones, V., Tar, K., et al. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1004968 · Cited by 46 · see citing works
Self-citationSenescence: Pathogenic Driver in Chronic Obstructive Pulmonary Disease
Rivas, M., Gupta, G., Costanzo, L., Ahmed, H., Wyman, A. E., & Geraghty, P. M. (2022) · Medicina · doi:10.3390/medicina58060817 · Cited by 46 · see citing works
Rapamycin maintains NAD+/NADH redox homeostasis in muscle cells
Zhang, Z., Xu, H. N., Li, S., Dávila, A., Chellappa, K., Davis, J. G., Guan, Y., Frederick, D. W., Chu, W., Zhao, H., et al. (2020) · Aging · doi:10.18632/aging.103954 · Cited by 38 · see citing works
Tumor promoter-induced cellular senescence: cell cycle arrest followed by geroconversion
Leontieva, O. V., & Blagosklonny, M. V. (2014) · Oncotarget · doi:10.18632/oncotarget.3011 · 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
Aging research using the common marmoset: Focus on aging interventions
Ross, C. N., & Salmon, A. B. (2018) · Nutrition and Healthy Aging · doi:10.3233/nha-180046 · Cited by 34 · see citing works
Genetics and Pharmacology of Longevity
Castillo-Quan, J. I., Kinghorn, K. J., & Bjedov, I. (2015) · Advances in genetics · doi:10.1016/bs.adgen.2015.06.002 · Cited by 37 · see citing works
Interventions to slow cardiovascular aging: Dietary restriction, drugs and novel molecules
Heiß, C., Spyridopoulos, I., & Haendeler, J. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.06.015 · Cited by 35 · see citing works
Antibiotics that target mitochondria extend lifespan in C. elegans
Bonuccelli, G., Brooks, D. R., Shepherd, S., Sotgia, F., & Lisanti, M. P. (2023) · Aging · doi:10.18632/aging.205229 · Cited by 32 · see citing works
Ross, C. N., Austad, S. N., Brasky, K., Brown, C. J., Forney, L. J., Gelfond, J., Lanford, R. E., Richardson, A. G., & Tardif, S. D. (2017) · Aging · doi:10.18632/aging.101340 · Cited by 32 · see citing works
Longevity-Promoting Pharmaceuticals: Is it a Time for Implementation?
Vaiserman, A. M., & Marotta, F. (2016) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2016.02.003 · Cited by 31 · see citing works
Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits
Yip, J., Chiang, G. S. H., Lee, I. C. J., Lehming-Teo, R., Dai, K., Dongol, L., Wang, L. Y.-T., Teo, D. W. X., Seah, G. T., & Lehming, N. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26010364 · Cited by 28 · see citing works
Balistreri, C. R. (2018) · Mediators of Inflammation · doi:10.1155/2018/3705389 · Cited by 27 · see citing works
Guo, D., Shen, Y., Li, W., Li, Q., Miao, Y., & Zhong, Y. (2020) · Aging · doi:10.18632/aging.102666 · Cited by 26 · see citing works
CD4+ T-Cell Senescence in Neurodegenerative Disease: Pathogenesis and Potential Therapeutic Targets
Gao, Y., Lu, Y., Liang, X., Zhao, M., Yu, X., Fu, H., & Yang, W. (2024) · Cells · doi:10.3390/cells13090749 · Cited by 26 · see citing works
Firdaus, Z., Singh, N., Prajapati, S. K., Krishnamurthy, S., & Singh, T. D. (2020) · Drug and Chemical Toxicology · doi:10.1080/01480545.2020.1833907 · Cited by 25 · see citing works
Gaspar, L. S., Sousa, C., Álvaro, A. R., Cavadas, C., & Mendes, A. F. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105369 · Cited by 24 · see citing works
Monoterpenes as Sirtuin-1 Activators: Therapeutic Potential in Aging and Related Diseases
Sousa, C., & Mendes, A. F. (2022) · Biomolecules · doi:10.3390/biom12070921 · Cited by 24 · see citing works
Olovnikov, A. M. (2015) · Current Aging Science · doi:10.2174/1874609808666150422114916 · Cited by 23 · see citing works
Atef, M. M., Emam, M. N., Gheit, R. E. A. E., El-Beltagi, E. M., Alshenawy, H. A., Radwan, D. A., Younis, R. L., & Abd‐Ellatif, R. N. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03559-3 · Cited by 22 · see citing works
Emerging uncertainty on the anti-aging potential of metformin
Keys, M. T., Hallas, J., Miller, R. A., Suissa, S., & Christensen, K. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102817 · Cited by 24 · see citing works
Metformin ameliorates the age‐related changes of d ‐galactose administration in ovariectomized mice
Fatemi, I., Heydari, S., Kaeidi, A., Shamsizadeh, A., Hakimizadeh, E., Khaluoi, A., & Allahtavakoli, M. (2018) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.12364 · Cited by 21 · see citing works
The Role of SOX Transcription Factors in Ageing and Age-Related Diseases
Stevanović, M. J., Lazic, A., Schwirtlich, M., & Ninković, D. S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24010851 · Cited by 19 · see citing works
Varela‐López, A., Romero‐Márquez, J. M., Navarro‐Hortal, M. D., Ramírez-Tortosa, C. L., Battino, M. A., Forbes-Hernández, T. Y., & Quiles, J. L. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2023.112221 · Cited by 21 · see citing works
Ross, C. N. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811829-0.00021-2 · Cited by 20 · see citing works
Nutrient Sensing and Redox Balance: GCN2 as a New Integrator in Aging
Falcón, P., Escandón, M., Brito, Á., & Matus, S. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/5730532 · Cited by 20 · see citing works
Six plant extracts delay yeast chronological aging through different signaling pathways
Lutchman, V., Dakik, P., McAuley, M., Cortes, B., Ferraye, G., Gontmacher, L., Graziano, D., Moukhariq, F.-Z., Simard, É., & Titorenko, V. I. (2016) · Oncotarget · doi:10.18632/oncotarget.10689 · Cited by 19 · see citing works
An essay on the nominal vs. real definitions of aging
Golubev, A. G. (2021) · Biogerontology · doi:10.1007/s10522-021-09926-x · Cited by 19 · see citing works
What is the evidence for stress resistance and slowed aging?
Hamilton, K. L., & Miller, B. F. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.06.001 · Cited by 19 · see citing works
Hakimizadeh, E., Zamanian, M. Y., Borisov, V. V., Giménez‐Llort, L., Ehsani, V., Kaeidi, A., Hassanshahi, J., Khajehasani, F., Movahedinia, S., & Fatemi, I. (2022) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.12752 · Cited by 18 · see citing works
Guo, D., Shen, Y., Li, W., Li, Q., Zhao, Y., Pan, C., Chen, B., Zhong, Y., & Miao, Y. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00320 · Cited by 17 · see citing works
6-Bromoindirubin-3’-oxime (6BIO) prevents myocardium from aging by inducing autophagy
Guo, D., Cheng, L., Shen, Y., Li, W., Li, Q., Zhong, Y., & Miao, Y. (2020) · Aging · doi:10.18632/aging.202253 · Cited by 17 · see citing works
A Deep-Learning Proteomic-Scale Approach for Drug Design
Overhoff, B., Falls, Z., Mangione, W., & Samudrala, R. (2021) · Pharmaceuticals · doi:10.3390/ph14121277 · Cited by 17 · see citing works
Aging-modulating treatments: from reductionism to a system-oriented perspective
Vaiserman, A. M. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00446 · Cited by 16 · see citing works
Teo, E., Fong, S., Tolwinski, N. S., & Gruber, J. (2020) · GeroScience · doi:10.1007/s11357-020-00169-1 · Cited by 16 · see citing works
Resveratrol Modulates Mitochondria Dynamics in Replicative Senescent Yeast Cells
Wang, I.-H., Chen, H., Wang, Y., Chang, K., Chen, Y., & Chang, C. (2014) · PLoS ONE · doi:10.1371/journal.pone.0104345 · Cited by 15 · see citing works
Kennedy, B. K., & Pennypacker, J. K. (2015) · Oncotarget · doi:10.18632/oncotarget.3173 · Cited by 15 · see citing works
Self-citationTherapeutic Manipulation of Ageing: Repurposing Old Dogs and Discovering New Tricks
Mallikarjun, V., & Swift, J. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.11.020 · Cited by 14 · see citing works
Chen, H., Tang, H., Zhang, X., Huang, J., Luo, N., Guo, Q., & Wang, X. (2024) · Revista Española de Cardiología (English Edition) · doi:10.1016/j.rec.2024.04.004 · Cited by 14 · see citing works
The TORC1 inhibitor Nprl2 protects age-related digestive function in Drosophila
Xi, J., Cai, J., Yang, C., Fu, Y., Wei, W., Zhang, Z., Zhuang, Z., Hao, Y., Lilly, M. A., & Wei, Y. (2019) · Aging · doi:10.18632/aging.102428 · Cited by 14 · see citing works
Krops, L. A., Bouma, A. J., van Nassau, F., Nauta, J., van den Akker‐Scheek, I., Bossers, W. J. R., Brügemann, J., Buffart, L. M., Diercks, R. L., de Groot, V., et al. (2020) · JMIR Research Protocols · doi:10.2196/19397 · Cited by 15 · see citing works
Gerosuppression in confluent cells
Leontieva, O. V., & Blagosklonny, M. V. (2014) · Aging · doi:10.18632/aging.100714 · Cited by 14 · see citing works
Singh, A. K., Peng, B., Chien, S.-T., Chan, C.-H., Deng, Y.-H., Pai, H., Wei, H.-J., Wang, M.-F., Wang, S., Wu, C.-Y., et al. (2023) · Biomaterials Science · doi:10.1039/d2bm01997c · Cited by 13 · see citing works
Birkisdóttir, M. B., van Galen, I., Brandt, R. M. C., Barnhoorn, S., van Vliet, N., van Dijk, C., Nagarajah, B., Imholz, S., van Oostrom, C. T., Reiling, E., et al. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.1005322 · Cited by 13 · see citing works
Chronic Mechanistic Target of Rapamycin Inhibition: Preventing Cancer to Delay Aging, or Vice Versa?
Sharp, Z. D., Curiel, T. J., & Livi, C. B. (2013) · Interdisciplinary topics in gerontology and geriatrics · doi:10.1159/000343625 · Cited by 11 · see citing works
mTOR inhibitors for treatment of low-risk prostate cancer
Liss, M. A., Rickborn, L., DiGiovanni, J., Bacich, D. J., deGraffenried, L. A., Parihar, M., Thompson, I. M., & Sharp, Z. D. (2018) · Medical Hypotheses · doi:10.1016/j.mehy.2018.06.004 · Cited by 12 · see citing works
Translational research on aging: clinical epidemiology as a bridge between the sciences
Callahan, C. M., Foroud, T., Saykin, A. J., Shekhar, A., & Hendrie, H. C. (2013) · Translational research · doi:10.1016/j.trsl.2013.09.002 · Cited by 11 · see citing works
Alpha-1 Antitrypsin Deficiency and Accelerated Aging: A New Model for an Old Disease?
Crossley, D., Stockley, R. A., & Sapey, E. (2019) · Drugs & Aging · doi:10.1007/s40266-019-00684-7 · Cited by 10 · see citing works
Dakik, P., Rodriguez, M. E. L., Junio, J. A. B., Mitrofanova, D., Medkour, Y., Tafakori, T., Taifour, T., Lutchman, V., Samson, E., Arlia‐Ciommo, A., et al. (2020) · Oncotarget · doi:10.18632/oncotarget.27615 · Cited by 10 · see citing works
Commentary: Life course epidemiology embraces geroscience
Ferrucci, L. (2016) · International Journal of Epidemiology · doi:10.1093/ije/dyw104 · Cited by 10 · see citing works
Park, M. S., Choi, J., Lee, W., Yang, Y. J., Kim, J., Lee, G.-J., Kim, S. S., Park, S. H., Kim, S. C., & Choi, J. W. (2015) · Oncotarget · doi:10.18632/oncotarget.3949 · Cited by 8 · see citing works
Motevalian, M., Maroof, N. T., Nematollahi, M. H., Khajehasani, F., & Fatemi, I. (2021) · PubMed Central · doi:10.22038/ijbms.2021.58502.12996 · Cited by 8 · see citing works
Longevity expectations in the pension fund, insurance, and employee benefits industries
Zhavoronkov, A. A. (2015) · Psychology Research and Behavior Management · doi:10.2147/prbm.s75440 · Cited by 8 · see citing works
Ji, J., Zhang, B., Zheng, J., Zhang, X., Hu, X., Zhu, H., Wang, P., & Lan, Z. (2025) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2025.119883 · Cited by 7 · see citing works
Design and Analysis of Pharmacological Studies in Aging
Clay, K. J., & Petrascheck, M. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0592-9_7 · Cited by 7 · see citing works
Wong, L. P., Alias, H., Tan, K. M., Wong, P., Murugan, D. D., Hu, Z., & Lin, Y. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1254470 · Cited by 6 · see citing works
A Genetic Variant of ASCT2 Hampers In Vitro RNA Splicing and Correlates with Human Longevity
D’Aquila, P., Crocco, P., Rango, F. D., Indiveri, C., Bellizzi, D., Rose, G., & Passarino, G. (2017) · Rejuvenation Research · doi:10.1089/rej.2017.1948 · Cited by 6 · see citing works
Report: NIA workshop on translating genetic variants associated with longevity into drug targets
Participants, O. B. O. W. S. A., Schork, N. J., & Raghavachari, N. (2018) · GeroScience · doi:10.1007/s11357-018-0046-7 · Cited by 6 · see citing works
Chen, H., Tang, H., Zhang, X., Huang, J., Luo, N., Guo, Q., & Wang, X. (2024) · Revista Española de Cardiología · doi:10.1016/j.recesp.2024.04.004 · Cited by 5 · see citing works
An Introductory Guide to Using Bloomington Drosophila Stock Center and FlyBase for Aging Research
Zheng, X. (2024) · Cells · doi:10.3390/cells13141192 · Cited by 5 · see citing works
Gupta, V., Crudu, A., Matsuoka, Y., Ghosh, S., Rozot, R., Marat, X., Jäger, S., Kitano, H., & Breton, L. (2019) · npj Systems Biology and Applications · doi:10.1038/s41540-019-0119-y · Cited by 5 · see citing works
Potential of nanoparticles and nanopolymers in treatment of age-associated diseases
Saadatpour, F., Mohammadipanah, F., Zohourian, N., & Hodjat, M. (2021) · Advances in Natural Sciences Nanoscience and Nanotechnology · doi:10.1088/2043-6262/ac42c7 · Cited by 3 · see citing works
Participatory Exercise Medicine and Personalized Healthcare
Ren, S., & Shen, B. (2022) · Springer eBooks · doi:10.1007/978-981-16-9162-1_2 · Cited by 4 · see citing works
International Investment in Geroscience
Leng, S. X., & Kennedy, B. K. (2019) · Public Policy & Aging Report · doi:10.1093/ppar/prz024 · Cited by 4 · see citing works
Self-citationOlshansky, S. J. (2019) · Springer eBooks · doi:10.1007/978-3-319-69892-2_397-1 · Cited by 4 · see citing works
Living healthily to 120: Implications for entrepreneurship
van Gelderen, M. (2025) · Journal of Business Venturing · doi:10.1016/j.jbusvent.2025.106512 · Cited by 3 · see citing works
Umekar, M. J., Qutub, M., Premchandani, T., Tatode, A., Taksansde, J., Singanwad, P., Kale, M. B., Maniyar, M. G., & Hussain, U. (2025) · Precision medication. · doi:10.1016/j.prmedi.2025.100051 · Cited by 3 · see citing works
Assessing chronological aging in Saccharomyces cerevisiae
Schulze, A., Zimmermann, A., Kainz, K., Egger, N. B., Bauer, M. A., Madeo, F., & Carmona‐Gutiérrez, D. (2023) · Methods in cell biology · doi:10.1016/bs.mcb.2022.09.006 · Cited by 3 · see citing works
- 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 · 2013: 2
- 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
- Health Sciences › Medicine › Physiology › 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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