Browsing by Author "Sinclair, David"

Now showing items 1-20 of 32

    • Aging: Past, Present and Future 

      Blagosklonny, Mikhail V.; Campisi, Judith; Sinclair, David Andrew (Impact Journals LLC, 2009)
      In his Foundation series, published in the 1950’s, Isaac Asimov imagined Civilization capable of colonizing the entire Universe. This feat is unlikely to occur. Strikingly, Asimov referred to a 70-old man as an old ...

    • Carboxamide SIRT1 Inhibitors Block DBC1 Binding via an Acetylation-Independent Mechanism 

      Loh, Christine; Gomes, Ana P; Li, Jun; Disch, Jeremy S; Ellis, James L; Vlasuk, George P; Sinclair, David; Hubbard, Basil; Gomes, Ana Catarina; Doyle, Taylor; Armor, Sean (Landes Bioscience, 2013)
      SIRT1 is an NAD+-dependent deacetylase that counteracts multiple disease states associated with aging and may underlie some of the health benefits of calorie restriction. Understanding how SIRT1 is regulated in vivo could ...

    • Controlled DNA double-strand break induction in mice reveals post-damage transcriptome stability 

      Kim, Jeongkyu; Sturgill, David; Tran, Andy D.; Sinclair, David A.; Oberdoerffer, Philipp (Oxford University Press, 2016)
      DNA double-strand breaks (DSBs) and their repair can cause extensive epigenetic changes. As a result, DSBs have been proposed to promote transcriptional and, ultimately, physiological dysfunction via both cell-intrinsic ...

    • Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging 

      Gomes, Ana P.; Price, Nathan L.; Ling, Alvin J.Y.; Moslehi, Javid; Montgomery, Magdalene K.; Rajman, Luis; White, James Patrick; Teodoro, João S.; Wrann, Christiane Dorothea; Hubbard, Basil P.; Mercken, Evi M.; Palmeira, Carlos M.; de Cabo, Rafael; Rolo, Anabela P.; Turner, Nigel; Bell, Eric L.; Sinclair, David Andrew (Elsevier BV, 2013)
      Ever since eukaryotes subsumed the bacterial ancestor of mitochondria, the nuclear and mitochondrial genomes have had to closely coordinate their activities, as each encode different subunits of the oxidative phosphorylation ...

    • Dietary restriction involves NAD+-dependent mechanisms and a shift toward oxidative metabolism 

      Moroz, Natalie; Carmona, Juan J; Anderson, Edward; Hart, Anne C; Sinclair, David A; Blackwell, T Keith (BlackWell Publishing Ltd, 2014)
      Interventions that slow aging and prevent chronic disease may come from an understanding of how dietary restriction (DR) increases lifespan. Mechanisms proposed to mediate DR longevity include reduced mTOR signaling, ...

    • Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric Activators 

      Hubbard, B. P.; Gomes, A. P.; Dai, H.; Li, Jun; Case, A. W.; Considine, T.; Riera, T. V.; Lee, J. E.; E, S. Y.; Lamming, D. W.; Pentelute, Brad Lether; Schuman, E. R.; Stevens, L. A.; Ling, A. J. Y.; Armour, S. M.; Michan, S.; Zhao, H.; Jiang, Y.; Sweitzer, S. M.; Blum, C. A.; Disch, J. S.; Ng, P. Y.; Howitz, K. T.; Rolo, A. P.; Hamuro, Y.; Moss, J.; Perni, R. B.; Ellis, J. L.; Vlasuk, G. P.; Sinclair, David Andrew (American Association for the Advancement of Science (AAAS), 2013)
      A molecule that treats multiple age-related diseases would have a major impact on global health and economics. The SIRT1 deacetylase has drawn attention in this regard as a target for drug design. Yet controversy exists ...

    • Flavonoid Apigenin Is an Inhibitor of the NAD+ase CD38: Implications for Cellular NAD+ Metabolism, Protein Acetylation, and Treatment of Metabolic Syndrome 

      Escande, Carlos; Nin, Veronica; Price, Nathan L.; Capellini, Verena; Gomes, Ana P.; Barbosa, Maria Thereza; O’Neil, Luke; White, Thomas A.; Sinclair, David A.; Chini, Eduardo N. (American Diabetes Association, 2013)
      Metabolic syndrome is a growing health problem worldwide. It is therefore imperative to develop new strategies to treat this pathology. In the past years, the manipulation of NAD+ metabolism has emerged as a plausible ...

    • Head to Head Comparison of Short-Term Treatment with the NAD+ Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in Obese Female Mice 

      Uddin, Golam M.; Youngson, Neil A.; Sinclair, David A.; Morris, Margaret J. (Frontiers Media S.A., 2016)
      Obesity is well known to be a major cause of several chronic metabolic diseases, which can be partially counteracted by exercise. This is due, in part, to an upregulation of mitochondrial activity through increased ...

    • Impact papers on aging in 2009 

      Blagosklonny, Mikhail V.; Campisi, Judy; Bartke, Andrzej; Blasco, Maria A.; Bonner, William M.; Bohr, Vilhelm A.; Jr, Robert M. Brosh; Brunet, Anne; Donehower, Lawrence A.; Finch, Caleb E.; Finkel, Toren; Gorospe, Myriam; Gudkov, Andrei V.; Hall, Michael N.; Hekimi, Siegfried; Helfand, Stephen L.; Karlseder, Jan; Kenyon, Cynthia; Kroemer, Guido; Longo, Valter; Nussenzweig, Andre; Osiewacz, Heinz D.; Peeper, Daniel S.; Rando, Thomas A.; Rudolph, K Lenhard; Sassone-Corsi, Paolo; Serrano, Manuel; Sharpless, Norman E.; Skulachev, Vladimir P.; Tower, John; Verdin, Eric; Vijg, Jan; Sinclair, David Andrew; DePinho, Ronald A.; Tilly, Jonathan Lee (Impact Journals LLC, 2010)
      The editorial board of Aging reviews research papers published in 2009, which they believe have or will have a significant impact on aging research. Among many others, the topics include genes that accelerate aging or in ...

    • Interventions to Slow Aging in Humans: Are We Ready? 

      Longo, Valter D; Antebi, Adam; Bartke, Andrzej; Barzilai, Nir; Brown-Borg, Holly M; Caruso, Calogero; Curiel, Tyler J; de Cabo, Rafael; Franceschi, Claudio; Gems, David; Ingram, Donald K; Johnson, Thomas E; Kennedy, Brian K; Kenyon, Cynthia; Klein, Samuel; Kopchick, John J; Lepperdinger, Guenter; Madeo, Frank; Mirisola, Mario G; Mitchell, James R; Passarino, Giuseppe; Rudolph, Karl L; Sedivy, John M; Shadel, Gerald S; Sinclair, David A; Spindler, Stephen R; Suh, Yousin; Vijg, Jan; Vinciguerra, Manlio; Fontana, Luigi (John Wiley & Sons, Ltd, 2015)
      The workshop entitled ‘Interventions to Slow Aging in Humans: Are We Ready?’ was held in Erice, Italy, on October 8–13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus ...

    • The Lifespan Extension Effects of Resveratrol are Conserved in the Honey Bee and May Be Driven by a Mechanism Related to Caloric Restriction 

      Rascón, Brenda; Hubbard, Basil Paul; Sinclair, David Andrew; Amdam, Gro V. (Impact Journals LLC, 2012)
      Our interest in healthy aging and in evolutionarily conserved mechanisms of lifespan extension prompted us to investigate whether features of age-related decline in the honey bee could be attenuated with resveratrol. ...

    • Metformin improves healthspan and lifespan in mice 

      Martin-Montalvo, Alejandro; Mercken, Evi M.; Mitchell, Sarah J.; Palacios, Hector H.; Mote, Patricia L.; Scheibye-Knudsen, Morten; Gomes, Ana P.; Ward, Theresa M.; Minor, Robin K.; Blouin, Marie-José; Schwab, Matthias; Pollak, Michael; Zhang, Yongqing; Yu, Yinbing; Becker, Kevin G.; Bohr, Vilhelm A.; Ingram, Donald K.; Sinclair, David A.; Wolf, Norman S.; Spindler, Stephen R.; Bernier, Michel; de Cabo, Rafael (2013)
      Metformin is a drug commonly prescribed to treat patients with type 2 diabetes. Here we show that long-term treatment with metformin (0.1% w/w in diet) starting at middle age extends healthspan and lifespan in male mice, ...

    • Molecular Patterns and Signatures of Longevity 

      Ma, Siming (2016-05-02)
      Since their divergence from a common ancestor some 200 million years ago, mammals have undergone significant diversification in physiology, morphology, habitat, size, and longevity. The maximum lifespan of mammalian species ...

    • Neuronal sirtuin1 mediates retinal vascular regeneration in oxygen-induced ischemic retinopathy 

      Chen, Jing; Michan, Shaday; Juan, Aimee M.; Hurst, Christian G.; Hatton, Colman J.; Pei, Dorothy T.; Joyal, Jean-Sebastien; Evans, Lucy P.; Cui, Zhenghao; Stahl, Andreas; Sapieha, Przemyslaw; Sinclair, David Andrew; Smith, Lois Elaine Hodgson (Springer Science + Business Media, 2013)
      Regeneration of blood vessels in ischemic neuronal tissue is critical to reduce tissue damage in diseases. In proliferative retinopathy, initial vessel loss leads to retinal ischemia, which can induce either regrowth of ...

    • Nicotinamide Impairs Entry into and Exit from Meiosis I in Mouse Oocytes 

      Riepsamen, Angelique; Wu, Lindsay; Lau, Laurin; Listijono, Dave; Ledger, William; Sinclair, David; Homer, Hayden (Public Library of Science, 2015)
      Following exit from meiosis I, mammalian oocytes immediately enter meiosis II without an intervening interphase, accompanied by rapid reassembly of a bipolar spindle that maintains condensed chromosomes in a metaphase ...

    • O-GlcNAcylation regulates breast cancer metastasis via SIRT1 modulation of FOXM1 pathway 

      Ferrer, Christina M.; Lu, Tong Y.; Bacigalupa, Zachary A.; Katsetos, Christos D.; Sinclair, David A.; Reginato, Mauricio J. (2016)
      Tumors utilize aerobic glycolysis to support growth and invasion. However, the molecular mechanisms that link metabolism with invasion are not well understood. The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) ...

    • Protective effects of sirtuins in cardiovascular diseases: from bench to bedside 

      Winnik, Stephan; Auwerx, Johan; Sinclair, David A.; Matter, Christian M. (Oxford University Press, 2015)
      Sirtuins (Sirt1–Sirt7) comprise a family of nicotinamide adenine dinucleotide (NAD+)-dependent enzymes. While deacetylation reflects their main task, some of them have deacylase, adenosine diphosphate-ribosylase, demalonylase, ...

    • Restoration of normal embryogenesis by mitochondrial supplementation in pig oocytes exhibiting mitochondrial DNA deficiency 

      Cagnone, Gael L. M.; Tsai, Te-Sha; Makanji, Yogeshwar; Matthews, Pamela; Gould, Jodee; Bonkowski, Michael S.; Elgass, Kirstin D.; Wong, Ashley S. A.; Wu, Lindsay E.; McKenzie, Matthew; Sinclair, David A.; John, Justin C. St. (Nature Publishing Group, 2016)
      An increasing number of women fail to achieve pregnancy due to either failed fertilization or embryo arrest during preimplantation development. This often results from decreased oocyte quality. Indeed, reduced mitochondrial ...

    • Resveratrol improves health and survival of mice on a high-calorie diet 

      Baur, Joseph A.; Pearson, Kevin J.; Price, Nathaniel O; Jamieson, Hamish A.; Lerin, Carles; Kalra, Avash; Prabhu, Vinayakumar V.; Allard, Joanne S.; Lopez-Lluch, Guillermo; Lewis, Kaitlyn; Pistell, Paul J.; Poosala, Suresh; Becker, Kevin G.; Boss, Olivier; Gwinn, Dana; Wang, Mingyi; Ramaswamy, Sharan; Fishbein, Kenneth W.; Spencer, Richard; Lakatta, Edward G.; Le Couteur, David; Shaw, Reuben J.; Navas, Placido; Puigserver, Pere Puigserver; Ingram, Donald K.; de Cabo, Rafael; Sinclair, David Andrew (Nature Publishing Group, 2006)
      Resveratrol (3,5,4′-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent ...

    • Resveratrol Inhibits Pathologic Retinal Neovascularization in Vldlr -/- Mice 

      Hua, Jing; Guerin, Karen I.; Chen, Jing; Michán, Shaday; Stahl, Andreas; Krah, Nathan M.; Seaward, Molly R.; Dennison, Roberta; Juan, Aimee M.; Hatton, Colman J.; Sapieha, Przemyslaw; Sinclair, David Andrew; Smith, Lois Elaine Hodgson (Association for Research in Vision and Ophthalmology (ARVO), 2011)
      PURPOSE: Macular telangiectasia (MacTel) is a vision-threatening retinal disease with unknown pathogenesis and no approved treatment. Very low-density lipoprotein receptor mutant mice (Vldlr(-/-)) exhibit critical features ...