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Chapter 2 - The biology of aging

from Section I - General approach to the care of the elderly

Published online by Cambridge University Press:  05 June 2016

Jan Busby-Whitehead
Affiliation:
University of North Carolina
Christine Arenson
Affiliation:
Thomas Jefferson University, Philadelphia
Samuel C. Durso
Affiliation:
The Johns Hopkins University School of Medicine
Daniel Swagerty
Affiliation:
University of Kansas
Laura Mosqueda
Affiliation:
University of Southern California
Maria Fiatarone Singh
Affiliation:
University of Sydney
William Reichel
Affiliation:
Georgetown University, Washington DC
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Summary

The aging process has been studied at the molecular and physiologic level for decades, and many theories have been proposed for why this universal phenomenon evolved. Multiple tissue-level changes occur with aging, including chronic, “sterile” inflammation; cellular senescence; macromolecular damage, and progenitor cell function decline. These changes underlie age-related pathologies that lead to a decline in global function of the individual. In the study of aging biology, there is much to be learned from exceptionally long-lived humans, such as centenarians, as well as animal models of exceptional longevity, like the naked mole rat. In addition, attention should be paid to disparities that exist in life span even within the United States. Importantly, drugs have been developed that extend life span, enhance health span, or delay or alleviate age-related conditions in mice. The field of aging biology is more poised than ever to turn toward the translation of basic research findings into clinical applications that might extend human health and life span.
Type
Chapter
Information
Reichel's Care of the Elderly
Clinical Aspects of Aging
, pp. 17 - 27
Publisher: Cambridge University Press
Print publication year: 2016

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References

Goldman, DP, Cutler, D, Rowe, JW, Michaud, PC, Sullivan, J, Peneva, D, et al. Substantial health and economic returns from delayed aging may warrant a new focus for medical research. Health Affairs. 2013 Oct; 32(10):1698–705. PubMed PMID: 24101058. Pubmed Central PMCID: 3938188.Google Scholar
Kirkland, JL. Translating advances from the basic biology of aging into clinical application. Experimental Gerontology. 2013 Jan;48(1):15. PubMed PMID: 23237984. Pubmed Central PMCID: 3543864.Google Scholar
Medvedev, ZA. An attempt at a rational classification of theories of aging. Biological Reviews. 1990 August 1990;65(3):375–98.Google Scholar
Kirkwood, TB, Austad, SN. Why do we age? Nature. 2000 Nov 9;408(6809):233–8. PubMed PMID: 11089980.Google Scholar
Williams, GC. Pleiotropy, natural selection, and the evolution of senescence. Evolution; International Journal of Organic Evolution. 1957;11(4):398411.Google Scholar
Kirkwood, TB. Evolution of ageing. Nature. 1977 Nov 24;270(5635):301–4. PubMed PMID: 593350.Google Scholar
Kirkwood, TB, Holliday, R. The evolution of ageing and longevity. Proceedings of the Royal Society of London Series B, Containing papers of a Biological Character Royal Society. 1979 Sep 21;205(1161):531–46. PubMed PMID: 42059.Google Scholar
Orgel, LE. The maintenance of the accuracy of protein synthesis and its relevance to ageing: a correction. Proceedings of the National Academy of Sciences of the United States of America. 1970 Nov;67(3):1476. PubMed PMID: 5274472. Pubmed Central PMCID: 283377.Google Scholar
Guarente, L, Kenyon, C. Genetic pathways that regulate ageing in model organisms. Nature. 2000 Nov 9;408(6809):255–62. PubMed PMID: 11089983.Google Scholar
Perls, TT, Wilmoth, J, Levenson, R, Drinkwater, M, Cohen, M, Bogan, H, et al. Life-long sustained mortality advantage of siblings of centenarians. Proceedings of the National Academy of Sciences of the United States of America. 2002 Jun 11;99(12):8442–7. PubMed PMID: 12060785. Pubmed Central PMCID: 123086.Google Scholar
Schoenmaker, M, de Craen, AJ, de Meijer, PH, Beekman, M, Blauw, GJ, Slagboom, PE, et al. Evidence of genetic enrichment for exceptional survival using a family approach: the Leiden Longevity Study. European Journal of Human Genetics: EJHG. 2006 Jan;14(1):7984. PubMed PMID: 16251894.Google Scholar
Brown-Borg, HM. Hormonal regulation of longevity in mammals. Ageing Research Reviews. 2007 May;6(1):2845. PubMed PMID: 17360245. Pubmed Central PMCID: 1978093.Google Scholar
Brown-Borg, HM, Borg, KE, Meliska, CJ, Bartke, A. Dwarf mice and the ageing process. Nature. 1996 Nov 7;384(6604):33. PubMed PMID: 8900272.CrossRefGoogle ScholarPubMed
Coschigano, KT, Clemmons, D, Bellush, LL, Kopchick, JJ. Assessment of growth parameters and lifespan of GHR/BP gene-disrupted mice. Endocrinology. 2000 Jul;141(7):2608–13. PubMed PMID: 10875265.Google Scholar
Guevara-Aguirre, J, Balasubramanian, P, Guevara-Aguirre, M, Wei, M, Madia, F, Cheng, CW, et al. Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Science Translational Medicine. 2011 Feb 16;3(70):70ra13. PubMed PMID: 21325617. Pubmed Central PMCID: 3357623.Google Scholar
Suh, Y, Atzmon, G, Cho, MO, Hwang, D, Liu, B, Leahy, DJ, et al. Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proceedings of the National Academy of Sciences of the United States of America. 2008 Mar 4;105(9):3438–42. PubMed PMID: 18316725. Pubmed Central PMCID: 2265137.Google Scholar
Sutter, NB, Bustamante, CD, Chase, K, Gray, MM, Zhao, K, Zhu, L, et al. A single IGF1 allele is a major determinant of small size in dogs. Science. 2007 Apr 6;316(5821):112–5. PubMed PMID: 17412960. Pubmed Central PMCID: 2789551.Google Scholar
Jackola, DR, Ruger, JK, Miller, RA. Age-associated changes in human T cell phenotype and function. Aging. 1994 Feb;6(1):2534. PubMed PMID: 8043623.Google Scholar
Franceschi, C, Capri, M, Monti, D, Giunta, S, Olivieri, F, Sevini, F, et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mechanisms of Ageing and Development. 2007 Jan;128(1):92105. PubMed PMID: 17116321.CrossRefGoogle ScholarPubMed
Harman, D. Aging: a theory based on free radical and radiation chemistry. Journal of Gerontology. 1956 Jul;11(3):298300. PubMed PMID: 13332224.Google Scholar
Edrey, YH, Hanes, M, Pinto, M, Mele, J, Buffenstein, R. Successful aging and sustained good health in the naked mole rat: a long-lived mammalian model for biogerontology and biomedical research. ILAR Journal / National Research Council, Institute of Laboratory Animal Resources. 2011;52(1):4153. PubMed PMID: 21411857.Google Scholar
Tchkonia, T, Zhu, Y, van Deursen, J, Campisi, J, Kirkland, JL. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest. 2013 Mar 1;123(3):966–72. PubMed PMID: 23454759. Pubmed Central PMCID: 3582125.Google Scholar
Harris, TB, Ferrucci, L, Tracy, RP, Corti, MC, Wacholder, S, Ettinger, WH Jr., et al. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. American Journal of Medicine. 1999 May;106(5):506–12. PubMed PMID: 10335721.Google Scholar
Cohen, HJ, Pieper, CF, Harris, T, Rao, KMK, Currie, MS. The association of plasma IL-6 levels with functional disability in community-dwelling elderly. J Gerontol A Biol. 1997 Jul;52(4):M201–M8. PubMed PMID: WOS:A1997XK46700011. English.Google Scholar
Leng, S, Chaves, P, Koenig, K, Walston, J. Serum interleukin-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: a pilot study. Journal of the American Geriatrics Society. 2002 Jul;50(7):1268–71. PubMed PMID: 12133023.CrossRefGoogle ScholarPubMed
Coppe, JP, Patil, CK, Rodier, F, Sun, Y, Munoz, DP, Goldstein, J, et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biology. 2008 Dec 2;6(12):2853–68. PubMed PMID: 19053174. Pubmed Central PMCID: 2592359.Google Scholar
Campisi, J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell. 2005 Feb 25;120(4):513–22. PubMed PMID: 15734683. Epub 2005/03/01. eng.Google Scholar
Dimri, GP, Lee, X, Basile, G, Acosta, M, Scott, G, Roskelley, C, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proceedings of the National Academy of Sciences of the United States of America. 1995 Sep 26;92(20):9363–7. PubMed PMID: 7568133. Pubmed Central PMCID: 40985.Google Scholar
Stout, MB, Tchkonia, T, Pirtskhalava, T, Palmer, AK, List, EO, Berryman, DE, et al. Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice. Aging. 2014 Jul; 6(7):575–86. Pubmed Central PMCID: 4153624.Google Scholar
Jeyapalan, JC, Sedivy, JM. Cellular senescence and organismal aging. Mechanisms of Ageing and Development. 2008 Jul–Aug;129(7–8):467–74. PubMed PMID: 18502472. Pubmed Central PMCID: PMC3297662. Epub 2008/05/27. eng.Google Scholar
Baker, DJ, Wijshake, T, Tchkonia, T, LeBrasseur, NK, Childs, BG, van de Sluis, B, et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2011 Nov 10;479(7372):232–6. PubMed PMID: 22048312. Epub 2011/11/04. eng.Google Scholar
Garinis, GA, van der Horst, GT, Vijg, J, Hoeijmakers, JH. DNA damage and ageing: new-age ideas for an age-old problem. Nature Cell Biology. 2008 Nov;10(11):1241–7. PubMed PMID: 18978832.Google Scholar
Dai, DF, Chiao, YA, Marcinek, DJ, Szeto, HH, Rabinovitch, PS. Mitochondrial oxidative stress in aging and healthspan. Longevity & Healthspan. 2014;3:6. PubMed PMID: 24860647. Pubmed Central PMCID: 4013820.Google Scholar
Morin, P Jr., Dubuc, A, Storey, KB. Differential expression of microRNA species in organs of hibernating ground squirrels: a role in translational suppression during torpor. Biochimica et Biophysica Acta. 2008 Oct;1779(10):628–33. PubMed PMID: 18723136.Google Scholar
Rubinsztein, DC, Marino, G, Kroemer, G. Autophagy and aging. Cell. 2011 Sep 2;146(5):682–95. PubMed PMID: 21884931.Google Scholar
Madeo, F, Tavernarakis, N, Kroemer, G. Can autophagy promote longevity? Nature Cell Biology. 2010 Sep;12(9):842–6. PubMed PMID: 20811357.CrossRefGoogle ScholarPubMed
Ramasamy, R, Vannucci, SJ, Yan, SS, Herold, K, Yan, SF, Schmidt, AM. Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. Glycobiology. 2005 Jul;15(7):16R28R. PubMed PMID: 15764591.Google Scholar
Takeuchi, M, Bucala, R, Suzuki, T, Ohkubo, T, Yamazaki, M, Koike, T, et al. Neurotoxicity of advanced glycation end-products for cultured cortical neurons. Journal of Neuropathology and Experimental Neurology. 2000 Dec;59(12):1094–105. PubMed PMID: 11138929.Google Scholar
Woltjer, RL, Maezawa, I, Ou, JJ, Montine, KS, Montine, TJ. Advanced glycation endproduct precursor alters intracellular amyloid-beta/A beta PP carboxy-terminal fragment aggregation and cytotoxicity. Journal of Alzheimer’s Disease. 2003 Dec;5(6):467–76. PubMed PMID: 14757937.Google Scholar
Goh, SY, Cooper, ME. Clinical review: the role of advanced glycation end products in progression and complications of diabetes. Journal of Clinical Endocrinology and Metabolism. 2008 Apr;93(4):1143–52. PubMed PMID: 18182449.Google Scholar
Slawik, M, Vidal-Puig, AJ. Lipotoxicity, overnutrition and energy metabolism in aging. Ageing Research Reviews. 2006 May;5(2):144–64. PubMed PMID: 16630750.Google Scholar
Guo, W, Pirtskhalava, T, Tchkonia, T, Xie, W, Thomou, T, Han, J, et al. Aging results in paradoxical susceptibility of fat cell progenitors to lipotoxicity. American Journal of Physiology Endocrinology and Metabolism. 2007 Apr;292(4):E1041–51. PubMed PMID: 17148751.Google Scholar
Wang, ZW, Pan, WT, Lee, Y, Kakuma, T, Zhou, YT, Unger, RH. The role of leptin resistance in the lipid abnormalities of aging. FASEB Journal. 2001 Jan;15(1):108–14. PubMed PMID: 11149898.CrossRefGoogle ScholarPubMed
Jones, DL, Rando, TA. Emerging models and paradigms for stem cell ageing. Nature Cell Biology. 2011 May;13(5):506–12. PubMed PMID: 21540846. Pubmed Central PMCID: 3257978.Google Scholar
Rossi, DJ, Bryder, D, Zahn, JM, Ahlenius, H, Sonu, R, Wagers, AJ, et al. Cell intrinsic alterations underlie hematopoietic stem cell aging. Proceedings of the National Academy of Sciences of the United States of America. 2005 Jun 28;102(26):9194–9. PubMed PMID: 15967997. Pubmed Central PMCID: 1153718.Google Scholar
Gimble, JM, Nuttall, ME. The relationship between adipose tissue and bone metabolism. Clinical Biochemistry. 2012 Aug;45(12):874–9. PubMed PMID: 22429519.Google Scholar
Conboy, IM, Conboy, MJ, Wagers, AJ, Girma, ER, Weissman, IL, Rando, TA. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature. 2005 Feb 17;433(7027):760–4. PubMed PMID: 15716955. Epub 2005/02/18. eng.Google Scholar
Fries, JF. Aging, natural death, and the compression of morbidity. New England Journal of Medicine. 1980 Jul 17;303(3):130–5. PubMed PMID: 7383070.Google Scholar
Fries, JF, Bruce, B, Chakravarty, E. Compression of morbidity 1980–2011: a focused review of paradigms and progress. Journal of Aging Research. 2011;2011:110. PubMed PMID: 21876805. Pubmed Central PMCID: 3163136.Google Scholar
Andersen, SL, Sebastiani, P, Dworkis, DA, Feldman, L, Perls, TT. Healthspan approximates lifespan among many supercentenarians: compression of morbidity at the approximate limit of lifespan. Journals of Gerontology: Series A, Biological Sciences and Medical Sciences. 2012 Apr;67(4):395405. PubMed PMID: 22219514. Pubmed Central PMCID: 3309876.Google Scholar
Sebastiani, P, Solovieff, N, Dewan, AT, Walsh, KM, Puca, A, Hartley, SW, et al. Genetic signatures of exceptional longevity in humans. PloS One. 2012;7(1):e29848. PubMed PMID: 22279548. Pubmed Central PMCID: 3261167.Google Scholar
Schachter, F, Faure-Delanef, L, Guenot, F, Rouger, H, Froguel, P, Lesueur-Ginot, L, et al. Genetic associations with human longevity at the APOE and ACE loci. Nature Genetics. 1994 Jan;6(1):2932. PubMed PMID: 8136829.Google Scholar
Kenyon, NS, Russell, TR, Xu, XM, Knapp, J, Ricordi, C. Enrichment of hematopoietic stem cells from human vertebral body marrow. Transplantation Proceedings. 1997 Jun;29(4):1951. PubMed PMID: 9193467.Google Scholar
Willcox, BJ, Donlon, TA, He, Q, Chen, R, Grove, JS, Yano, K, et al. FOXO3A genotype is strongly associated with human longevity. Proceedings of the National Academy of Sciences of the United States of America. 2008 Sep 16;105(37):13987–92. PubMed PMID: 18765803. Pubmed Central PMCID: 2544566.Google Scholar
Bluher, M, Kahn, BB, Kahn, CR. Extended longevity in mice lacking the insulin receptor in adipose tissue. Science. 2003 Jan 24;299(5606):572–4. PubMed PMID: 12543978.Google Scholar
Smith, RL, de Boer, R, Brul, S, Budovskaya, Y, van Spek, H. Premature and accelerated aging: HIV or HAART? Frontiers in Genetics. 2012;3:328. PubMed PMID: 23372574. Pubmed Central PMCID: 3556597.Google Scholar
Ness, KK, Krull, KR, Jones, KE, Mulrooney, DA, Armstrong, GT, Green, DM, et al. Physiologic frailty as a sign of accelerated aging among adult survivors of childhood cancer: a report from the St. Jude Lifetime Cohort Study. Journal of Clinical Oncology. 2013 Dec 20;31(36):4496–503. PubMed PMID: 24248696. Pubmed Central PMCID: 3871511.Google Scholar
Meeske, KA, Nelson, MB. The role of the long-term follow-up clinic in discovering new emerging late effects in adult survivors of childhood cancer. Journal of Pediatric Oncology Nursing. 2008 Jul–Aug;25(4):213–9. PubMed PMID: 18539912.Google Scholar
Meyer, J. Centenarians: 2010. Washington, DC: United States Census Bureau Special Reports 2010, No. C2010SR-03; 2012.Google Scholar
Ka’opua, LS, Braun, KL, Browne, CV, Mokuau, N, Park, CB. Why are Native Hawaiians underrepresented in Hawai’i’s older adult population? Exploring social and behavioral factors of longevity. Journal of Aging Research. 2011;2011:701232. PubMed PMID: 21966592. Pubmed Central PMCID: 3182069.Google Scholar
Arias, E. United States Life Tables, 2010. National Vital Statistics Reports. 2014;63(7):163. Pubmed PMID: 25383611.Google Scholar
Harrison, DE, Strong, R, Sharp, ZD, Nelson, JF, Astle, CM, Flurkey, K, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009 Jul 16;460(7253):392–5. PubMed PMID: 19587680. Pubmed Central PMCID: 2786175.Google Scholar
Miller, RA, Harrison, DE, Astle, CM, Baur, JA, Boyd, AR, de Cabo, R, et al. Rapamycin, but not resveratrol or simvastatin, extends lifespan of genetically heterogeneous mice. Journals of Gerontology: Series A, Biological Sciences and Medical Sciences. 2011 Feb;66(2):191201. PubMed PMID: 20974732. Pubmed Central PMCID: 3021372.Google Scholar
Strong, R, Miller, RA, Astle, CM, Baur, JA, de Cabo, R, Fernandez, E, et al. Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on lifespan of genetically heterogeneous mice. Journals of Gerontology: Series A, Biological Sciences and Medical Sciences. 2013 Jan;68(1):616. PubMed PMID: 22451473. Pubmed Central PMCID: 3598361.Google Scholar
Martin-Montalvo, A, Mercken, EM, Mitchell, SJ, Palacios, HH, Mote, PL, Scheibye-Knudsen, M, et al. Metformin improves healthspan and lifespan in mice. Nature Communications. 2013;4:2192. PubMed PMID: 23900241. Pubmed Central PMCID: 3736576.Google Scholar
Strong, R, Miller, RA, Astle, CM, Floyd, RA, Flurkey, K, Hensley, KL, et al. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice. Aging Cell. 2008 Oct;7(5):641–50. PubMed PMID: 18631321. Pubmed Central PMCID: 2695675.Google Scholar
Harrison, DE, Strong, R, Allison, DB, Ames, BN, Astle, CM, Atamna, H, et al. Acarbose, 17-alpha-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males. Aging Cell. 2014 Apr;13(2):273–82. PubMed PMID: 24245565. Pubmed Central PMCID: 3954939.CrossRefGoogle ScholarPubMed
Fontana, L, Partridge, L, Longo, VD. Extending healthy lifespan – from yeast to humans. Science. 2010 Apr 16;328(5976):321–6. PubMed PMID: 20395504. Pubmed Central PMCID: 3607354.Google Scholar
Mattison, JA, Roth, GS, Beasley, TM, Tilmont, EM, Handy, AM, Herbert, RL, et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature. 2012 Sep 13;489(7415):318–21. PubMed PMID: 22932268. Pubmed Central PMCID: 3832985.Google Scholar
Colman, RJ, Anderson, RM, Johnson, SC, Kastman, EK, Kosmatka, KJ, Beasley, TM, et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009 Jul 10;325(5937):201–4. PubMed PMID: 19590001. Pubmed Central PMCID: 2812811.Google Scholar
Dirks, AJ, Leeuwenburgh, C. Caloric restriction in humans: potential pitfalls and health concerns. Mechanisms of Ageing and Development. 2006 Jan;127(1):17. PubMed PMID: 16226298.Google Scholar

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