Chapter 23 Aging and Senescence

Literature Cited

Arking, R. 1998. The Biology of Aging, 2nd Ed. Sinauer Associates, Sunderland, MA.

Atzmon, G. and 14 others. 2010. Evolution in health and medicine Sackler colloquium: Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians. Proc. Natl. Acad. Sci. USA 107 Suppl 1: 710–1717.
PubMed Link

Bailey, K. J., A. Y. Maslov and S. C. Pruitt. 2004. Accumulation of mutations and somatic selection in aging neural stem/progenitor cells. Aging Cell 3: 391–397.
PubMed Link

Baker, D. J. and 7 others. 2011. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479: 232–236.
PubMed Link

Bavestrello, G., C. Sommer and M. Sar·. 1992. Bi-directional conversion inTurritopsis nutriculaIn J. Bouillon et al. (eds.), Aspects of Hydrozoan Biology,Sci. Mar. 56 (2–3): 137–140.

Bernardes de Jesus, B. and 6 others. 2012. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer.EMBO Mol. Med. 4:691–704.
PubMed Link

Blackburn, E. H., E. S. Epel and J. Lin. 2015. Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection. Science 350: 1193–1198.
PubMed Link

Blüher, M., B. B. Kahn and C. R. Kahn. 2003. Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299: 572–574. 
PubMed Link

Boehm, A. M. and 10 others. 2012. FoxO is a critical regulator of stem cell maintenance in immortal HydraProc. Natl. Acad. Sci. USA 109: 19697–19702
PubMed Link

Chen, C., Y. Lui and P. Zheng. 2009. mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Sci Signal. 2: ra75.
PubMed Link

Clancy, D. J. and 7 others. 2001. Extension of life-span by loss of Chico, aDrosophila insulin receptor substrate protein. Science 292: 104–106.
PubMed Link

Coles, L. S. 2004. Demography of human supercentenarians. J. Gerontol. A: Biol. Sci. Med. Sci. 59: B579- 586.
PubMed Link

Colman, R. J. and 10 others. 2009. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325: 201–204.
PubMed Link

Conboy, I. M. and T. A. Rando. 2012. Heterochronic parabiosis for the study of the effects of aging on stem cells and their niches. Cell Cycle 11: 2260–2267.
PubMed Link

Conboy, I. M., M. J. Conboy, A. J. Wagers, E. R. Girma, I. L. Weissman and T. A. Rando. 2005. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433: 760–764.
PubMed Link

Congdon, J. D., R. D. Nagle, O. M. Kinney, R. C. van Loben Sels, T. Quinter and D. W. Tinkle. 2003. Testing hypotheses of aging in long lived painted turtles (Chrysemys picta). Exp. Gerontol. 38: 765–772.
PubMed Link

Coppedè, F. and L. Migliore. 2010. DNA repair in premature aging disorders and neurodegeneration. Curr. Aging Sci. 3: 3–19.
PubMed Link

de Boer, J. and 11 others. 2002. Premature aging in mice deficient in DNA repair and transcription. Science 296: 1276–1279.
PubMed Link

Feng, J., F. Bussièe and S. Hekimi. 2001. Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegansDev. Cell 1: 633–644.
PubMed Link

Fraga, M. F. and 20 others. 2005. Epigenetic differences arise during the lifetime of monozygotic twins. Proc. Natl. Acad. Sci. USA 102: 10604–10609.
PubMed Link

Gems, D. and 7 others. 1998. Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegansGenetics 150: 129–155.
PubMed Link

Gerisch, B., C. Weitzel, C. Kober-Eisermann, V. Rottiers and A. Antebi. 2001. A hormonal signaling pathway influencing C. elegans metabolism, reproductive development, and life span. Dev. Cell 1: 841–851.
PubMed Link

Giannakou, M. E., M. Goss, M. A. Junger, E. Hafen, S. J. Leevers and L. Partridge. 2004. Long-lived Drosophila with overexpressed dFoxo in adult fat body. Science 305: 361.
PubMed Link

Girondot, M. and Garcia, J. 1998 Senescence and longevity in turtles: What telomeres tell us. In: R. Guyétant, R. and C. Miaud (eds.) Current Studies in Herpetology, Societa Europea Herpetologica, Le Bouget du Lac, France. 133–137.

Gjoneska, E., A. R. Pfenning, H. Mathys, G. Quon, A. Kundaje, L.-H. Tsai and M. Kellis. 2015. Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer’s disease. Nature 518: 365–369.
PubMed Link

Guarente, L. and C. Kenyon. 2000. Genetic pathways that regulate ageing in model organisms. Nature 408: 255–262.
PubMed Link

Gorbunova, V., A. Seluanov, Z. Mao and C. Hine. 2007. Changes in DNA repair during aging. Nucl. Acids Res. 35: 7466–7474.
PubMed Link

Halloran, J. and 9 others. 2012. Chronic inhibition of mammalian target of rapamycin by rapamycin modulates cognitive and non-cognitive components of behavior throughout lifespan in mice. Neuroscience 223: 102–113.
PubMed Link

Hannum, G. and 15 others. 2013. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol. Cell 49: 359–67.
PubMed Link

Harrison, D. E. and 13 others. 2009. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice.Nature 460: 392–395.
PubMed Link

Hart, R. and R. B. Setlow. 1974. Correlation between deoxyribonucleic acid excision repair and life-span in a number of mammalian species. Proc. Natl. Acad. Sci. USA 71: 2169–2173.
PubMed Link

Hatase, H. and 7 others. 2008. Shorter telomere length with age in the loggerhead turtle: A new hope for live sea turtle age estimation. Genes Genet. Syst. 83: 423–426.
PubMed Link

Herman, W. S. and M. Tatar. 2001. Juvenile hormone regulation of longevity in the migratory monarch butterfly. Proc. Biol. Sci. 268: 2509–2514. 
PubMed Link

Holzenberger, M. and 7 others. 2003. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421: 182–186.
PubMed Link

Honda, Y. and S. Honda. 1999. The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegansFASEB J. 13: 1385–1393.
PubMed Link

Horvath, S. 2013. DNA methylation age of human tissues and cell types. Genome Biol. 14: R115.
PubMed Link

Howitz, K. T. and 11 others. 2003. Small molecule activators of sirtuins extendSaccharomyces cerevisiae lifespan. Nature 425: 191–196.
PubMed Link

Hsin, H. and C. Kenyon. 1999. Signals from the reproductive system regulate the lifespan of C. elegansNature 399: 362–365.
PubMed Link

Hwangbo, D. S., B. Gersham, M.-P. Tu, M. Palmer, and M. Tatar. 2004.Drosophila dFOXO controls lifespan and regulates insulin signaling in brain and fat body. Nature 429: 562–566. 
PubMed Link

Issa, J.-P. J., Y. L. Ottaviano, P. Celano, S. R. Hamilton, N. E. Davidson and S. B. Baylin. 1994. Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nature Genetics 7: 536–540.
PubMed Link

Jaskelioff, M. and 12 others. 2011. Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature 469: 102–106.
PubMed Link

Jobs, S. 2005. Commencement Address, Stanford University, July 12, 2005
 Link

Johnson, S. C., P. S. Rabinovitch and M. Kaeberlein. 2013. mTOR is a key modulator of ageing and age-related disease. Nature 493: 338–345.
PubMed Link

Kamileri, I. and 6 others. 2012. Defective transcription initiation causes postnatal growth failure in a mouse model of nucleotide excision repair (NER) progeria. Proc. Natl. Acad. Sci. USA 109: 2995–3000.
PubMed Link

Katsimpardi L. and 9 others. 2014. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science 344: 630–634.
PubMed Link

Kenyon, C. 2001. A conserved regulatory system for aging. Cell 105: 165–168.
PubMed Link

Kenyon, C. J. 2010. The genetics of ageing. Nature 464: 504–512.
PubMed Link

Kim, J. and 8 others. 2007. Epigenetic changes in estrogen receptor b gene in atherosclerotic cardiovascular tissues and in vitro vascular senescence. Biochim. Biophys. Acta 1772: 72–80.
PubMed Link

Kimura, K. D., H. A. Tissenbaum, Y. Liu, and G. Ruvkun. 1997. Daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegansScience 277: 942–946. 
PubMed Link

Korzus, E., M. G. Rosenfeld and M. Mayford. 2004. CBP histone acetyltransferase activity is a critical component of memory consolidation.Neuron 42: 961–972
PubMed Link

Krivoruchko, A. and K. B. Storey. 2010. Forever young: Mechanisms of natural anoxia tolerance and potential links to longevity. Oxid. Med. Cell Longev. 3: 186–198.       
PubMed Link

Kurosu, H. and 15 others. 2005. Suppression of aging in mice by the hormone Klotho. Science 309: 1829–1833.
PubMed Link

Lamming, D. W. and 12 others. 2012. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science 335: 1638–1643.
PubMed Link

Loffredo, F. S. and 19 others. 2013. Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell 153: 828–839.
PubMed Link

Lutz, P. L., H. M. Prentice, and S. L. Milton. 2003. Is turtle longevity linked to enhanced mechanisms for surviving brain anoxia and reoxygenation? Exp. Gerontol. 38: 797–800. 
PubMed Link

Majumder, S. and 8 others. 2012. Lifelong rapamycin administration ameliorates age-dependent cognitive deficits by reducing IL-1β and enhancing NMDA signaling. Aging Cell 11: 326–335.
PubMed Link

Mattison, J. A. and 14 others. 2012. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 489: 318–321.
PubMed Link

Medawar, P. B. 1952. An Unsolved Problem of Biology. H. K. Lewis & Co., London.

Miller, C. A., S. L. Campbell and J. D. Sweatt. 2008. DNA methylation and histone acetylation work in concert to regulate memory formation and synaptic plasticity. Neurobiol. Learn Mem. 89: 599–603.
PubMed Link

Miller, J. K. 2001. Escaping senescence: Demographic data from the three-toed box turtle (Terrapene carolina triungis). Exp. Gerontol. 36: 829–832.
PubMed Link

Mitchell, J. R., E. Wood and K. Collins. 1999. A telomerase component is defective in the human disease dyskeratosis congenita. Nature 402: 551–555.
PubMed Link

Murray, V. and R. Holliday. 1981. Increased error frequency of DNA polymerases from senescent fibroblasts. J. Mol. Biol. 146: 55–76.
PubMed Link

Nishimura, E. K., S. R. Granter and D. E. Fisher. 2005. Mechanisms of hair graying: Incomplete melanocyte stem cell maintenance in the niche. Science307: 720–724.
PubMed Link

Oberdoerffer, P. and 17 others. 2008. SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell 135: 907–918.
PubMed Link

Orgel, L. E. 1963. The maintenence of the accuracy of protein synthesis and its relevance to ageing. Proc. Natl. Acad. Sci. USA 49: 517–521.
PubMed Link

Orr, W. S. and R. S. Sohal. 1994. Extension of lifespan by overexpression of superoxide dismutase and catalase in Drosophila melanogasterScience 263: 1128–1130.
PubMed Link

Pérez, V. I. and 6 others. 2009. Is the oxidative stress theory of aging dead? Biochim. Biophys. Acta 1790: 1005–1014.
PubMed Link

Parkes, T. L., A. J. Elia, D. Dickinson, A. J. Hilliker, J. P. Phillips and G. L. Boulianne. 1998. Extension of Drosophila lifespan by overexpression of human SOD1 in motoneurons. Nature Genet. 19: 171–174.
PubMed Link

Partridge, L. and D. Gems. 2002. Mechanisms of ageing: Public or private?Nature Rev. Genet. 3: 165–175.
PubMed Link

Peleg, S. and 15 others.  2010. Altered histone acetylation is associated with age-dependent memory impairment in mice. Science 328: 753–756.
PubMed Link

Penner, M. R. and 8 others. 2011. Age-related changes in Arc transcription and DNA methylation within the hippocampus. Neurobiol. Aging 32: 2198–2210.
PubMed Link

Pierce, S. B. and 12 others. 2001. Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family. Genes Dev. 15: 672–686.
PubMed Link

Piraino, S., F. Boero, B. Aeschbach and V. Schmid. 1996. Reversing the life cycle: Medusae transforming into polyps and cell transdifferentiation inTurritopsis nutricula (Cnidaria, Hydrozoa). Biol. Bull. 90: 302–312.

Poggioli, T and 15 others. 2016. Circulating growth factor 11/8 levels decline with age. Circulation Res. 118: 29–37.
PubMed Link

Post, W. S. and 8 others. 1999. Methylation of the estrogen receptor gene is associated with aging and atherosclerosis in the cardiovascular system.Cardiovasc. Res. 43: 985–991.
PubMed Link

Robinson, K. C. and D. E. Fisher. 2009. Specification and loss of melanocyte stem cells. Semin. Cell Dev. Biol. 20: 111–116.
PubMed Link

Rossi, D. J., D. Bryder, J. Seita, A. Nussenzweig, J. Hoeijmakers and I. L. Weissman. 2007. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature 447: 725–729.
PubMed Link

Rostand, J. 1962. The Substance of Man. Doubleday, Garden City, NJ. p. 9.

Roth, G. S. and 7 others. 2002. Biomarkers of caloric restriction may predict longevity in humans. Science 297: 811.
PubMed Link

Ruckh, J. M., J. W. Zhao, J. L. Shadrach, P. van Wijngaarden, T. N. Rao, A. J. Wagers and R. J. Franklin. 2012. Rejuvenation of regeneration in the aging central nervous system. Cell Stem Cell 10: 96–103.
PubMed Link

Schmich, J., Y. Kraus, D. De Vito, D. Graziussi, F. Boero and S. Piraino. 2007. Induction of reverse development in two marine hydrozoans. Int. J. Dev. Biol. 51: 45–56.
PubMed Link

Scudellari, M. 2015. Ageing research: Blood to blood. Nature 517: 426–429.
PubMed Link

Selman, C. and 20 others. 2009. Ribosomal protein S6 kinase 1 signaling regulates mammalian lifespan. Science 326: 140–144.
PubMed Link

Shen, J.-C. and L. A. Loeb. 2001. Unwinding the molecular basis of the Werner syndrome. Mech. Ageing Dev. 122: 921–944.
PubMed Link

Singh, N. P., C. E. Ogburn, N. S. Wolf, G. van Belle and G. M. Martin. 2001. DNA double-strand breaks in mouse kidney cells with age. Biogerontology 2: 261–70.
PubMed Link

Stein, P. K., A. Soare, T. E. Meyer, R. Cangemi, J. O. Holloszy and L Fontana. 2012. Caloric restriction may reverse age-related autonomic decline in humans.Aging Cell 11: 644–650,
PubMed Link

Sun, H., J. K. Jarow, I. D. Hickson and N. Mazels. 1998. The Blooms syndrome helicase unwinds G4 DNA. J. Biol. Chem. 273: 27587–27592.
PubMed Link

Sun, J. and J. Tower. 1999. FLP recombinase-mediated induction of Cu/Zn-superoxide dismutase transgene expression can extend the life span of adultDrosophila melanogaster flies. Mol. Cell Biol. 19: 216–228.
PubMed Link

Swank, M. W.and J. D. Sweatt. 2001. Increased histone acetyltransferase and lysine acetyltransferase activity and biphasic activation of the ERK/RSK cascade in insular cortex during novel taste learning. J. Neurosci. 21: 3383–3391.
PubMed Link

Sweatt, J. D. 2013. The emerging field of neuroepigenetics. Neuron 80: 624–632.
PubMed Link

Tatar, M., A. Kopelman, D. Epstein, M. P. Tu, C. M. Yin and R. S. Garofalo. 2001. A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science 292: 107–110.
PubMed Link

Tomás-Loba, A. and 12 others. 2008. Telomerase reverse transcriptase delays aging in cancer-resistant mice. Cell 135: 609–622.
PubMed Link

Tran, H. and 7 others. 2002. DNA repair pathways stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein. Science 296: 530–534.
PubMed Link

Tu, M.-P., C.-M. Yin and M. Tatar. 2005. Mutations in insulin signaling pathway alter juvenile hormone synthesis in Drosophila melanogasterGen. Comp. Endocrinol. 142: 347–356.
PubMed Link

Underwood, E. 2015. The final countdown. Science 350: 1188–1190.
PubMed Link

Ushijima, T., N. Watnabe, K. Shimizu, K. Miyamoto, T. Sugiura and A. Kaneda. 2005. Decreased fidelity in replicating CpG methylation patterns in cancer cells. Cancer Re. 65: 11–17.
PubMed Link

Van Raamsdonk, J. M.and S. Hekimi. 2012. Superoxide dismutase is dispensable for normal animal lifespan. Proc. Natl. Acad. Sci. USA 109: 5785–5790.
PubMed Link

Vijg, J. and J. Campisi. 2008. Puzzles, promises and a cure for ageing. Nature454: 1065–1071.
PubMed Link

Villeda, S. A. and 21 others. 2011. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature 477: 90–94.
PubMed Link

Villeda, S. A. and 17 others. 2014. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nature Med. 20: 659–663.
PubMed Link

Weismann, A. 1891. The duration of life. In E. B. Poulton, S. Schonland and A. E. Shipley (eds.), Essays on Heredity and Kindred Subjects, 2nd Ed. Oxford University Press, Oxford, pp. 163–256.

Wilson, A. J. and 7 others. 2007. Evidence for a genetic basis of aging in two wild vertebrate populations. Curr. Biol. 17: 2136–2142.
PubMed Link

Yilmaz, Ö. H. and 15 others. 2012. mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake. Nature 486: 490–495.
PubMed Link

Zhang, J. and Z. Ju. 2010. Telomere, DNA damage, and oxidative stress in stem cell aging. Birth Defects Res. C: Embryol. Today 90: 297–307.
PubMed Link

Zhang, P., M. Judy, S. J. Lee and C. Kenyon C. 2013. Direct and indirect gene regulation by a life-extending FOXO protein in C. elegans: Roles for GATA factors and lipid gene regulators. Cell Metab. 17: 85–100.
PubMed Link