Biology of Aging: Medical Perspective

Kwang-Il Kim

doi:10.5124/jkma.2007.50.3.216

J Korean Med Assoc > Volume 50(3); 2007 > Article

Kim: Biology of Aging: Medical Perspective

Focused Issue of This Month

Etiologies of Aging and Evidence-based Antiaging Therapy

Journal of the Korean Medical Association

Journal of the Korean Medical Association 2007; 50(3): 216-220.

Published online: March 31, 2007

DOI: http://dx.doi.org/10.5124/jkma.2007.50.3.216

Biology of Aging: Medical Perspective

Kwang-Il Kim, MD

Department of Internal Medicine, Seoul National University College of Medicine, Korea. kikim907@snubh.org

Abstract

Aging is the most familiar yet least understood aspect of human biology. It is usually defined as the time-dependent progressive loss of function leading to disability, dependence, morbidity, and mortality. Such a trait, which impairs the survival and fertility, is clearly disadvantageous for the individual, raising questions why and how it has evolved. Many theories have been proposed to explain the cause and mechanisms of aging; however, no single theory can clearly explain all the characteristics of aging, such as complexity, unpredictability, and diversity. Aging has been explained simply as an inevitable result of biological wear-and-tear. However, we now know that aging, like many other biological processes, is subject to the regulation by pathways that have been conserved during evolution. Changing the genes within these pathways can extend the life span dramatically. So it seems to be essential to investigate the multiplicity of mechanisms underlying aging to understand the biology in its essence.

Aging; Genomic; Telomere; Oxidative stress; Mitochondria

References

1. Kirkwood TB, Austad SN. Why do we age? Nature 2000;408:233-238.

2. Longo VD, Mitteldorf J, Skulachev VP. Opinion: programmed and altruistic ageing. Nat Rev Genet 2005;6:866-872.

3. Weinert BT, Timiras PS. Invited Review: Theories of aging. J Appl Physiol 2003;95:1706-1716.

4. Troen BR. The biology of aging. Mt Sinai J Med 2003;70:3-22.

5. Perls T, Kunkel LM, Puca AA. The genetics of exceptional human longevity. J Am Geriatr Soc 2002;50:359-368.

6. Terry DF, Wilcox M, McCormick MA, Lawler E, Perls TT. Cardiovascular advantages among the offspring of centenarians. J Gerontol A Biol Sci Med Sci 2003;58:M425-M431.

7. Karasik D, Demissie S, Cupples LA, Kiel DP. Disentangling the genetic determinants of human aging: biological age as an alternative to the use of survival measures. J Gerontol A Biol Sci Med Sci 2005;60:574-587.

8. Hasty P, Vijg J. Aging. Genomic priorities in aging. Science 2002;296:1250-1251.

9. Lieber MR, Karanjawala ZE. Ageing, repetitive genomes and DNA damage. Nat Rev Mol Cell Biol 2004;5:69-75.

10. Wong JM, Collins K. Telomere maintenance and disease. Lancet 2003;362:983-988.

11. Cawthon RM, Smith KR, O'Brien E, Sivatchenko A, Kerber RA. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 2003;361:393-395.

12. Lamberts SW, van den Beld AW, van der Lely AJ. The endocrinology of aging. Science 1997;278:419-424.

13. Tatar M, Bartke A, Antebi A. The endocrine regulation of aging by insulin-like signals. Science 2003;299:1346-1351.

14. Nair KS, Rizza RA, O'Brien P, Dhatariya K, Short KR, Nehra A, Vittone JL, Klee GG, Basu A, Basu R, Cobelli C, Toffolo G, Dalla Man C, Tindall DJ, Melton LJ 3rd, Smith GE, Khosla S, Jensen MD. DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med 2006;355:1647-1659.

15. Johnson FB, Sinclair DA, Guarente L. Molecular biology of aging. Cell 1999;96:291-302.

16. Sohal RS, Mockett RJ, Orr WC. Mechanisms of aging: an appraisal of the oxidative stress hypothesis. Free Radic Biol Med 2002;33:575-586.

17. Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 2005;308:1909-1911.

18. Kokoszka JE, Coskun P, Esposito LA, Wallace DC. Increased mitochondrial oxidative stress in the Sod2(+/-) mouse results in the age-related decline of mitochondrial function culminating in increased apoptosis. Proc Natl Acad Sci USA 2001;98:2278-2283.

19. Parkes TL, Elia AJ, Dickinson D, Hilliker AJ, Phillips JP, Boulianne GL. Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons. Nat Genet 1998;19:171-174.

20. Migliaccio E, Giorgio M, Mele S, Pelicci G, Reboldi P, Pandolfi PP, Lanfrancone L, Pelicci PG. The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 1999;402:309-313.

21. Napoli C, Martin-Padura I, de Nigris F, Giorgio M, Mansueto G, Somma P, Condorelli M, Sica G, De Rosa G, Pelicci P. Deletion of the p66Shc longevity gene reduces systemic and tissue oxidative stress, vascular cell apoptosis, and early atherogenesis in mice fed a high-fat diet. Proc Natl Acad Sci USA 2003;100:2112-2116.

22. Graiani G, Lagrasta C, Migliaccio E, Spillmann F, Meloni M, Madeddu P, Quaini F, Padura IM, Lanfrancone L, Pelicci P, Emanueli C. Genetic deletion of the p66Shc adaptor protein protects from angiotensin II-induced myocardial damage. Hypertension 2005;46:433-440.

23. Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA, Morrow JD, Van Remmen H, Sedivy JM, Yamasoba T, Tanokura M, Weindruch R, Leeuwenburgh C, Prolla TA. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 2005;309:481-484.

24. Trifunovic A, Hansson A, Wredenberg A, Rovio AT, Dufour E, Khvorostov I, Spelbrink JN, Wibom R, Jacobs HT, Larsson NG. From the Cover: Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc Natl Acad Sci USA 2005;102:17993-17998.

25. Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly YM, Gidlof S, Oldfors A, Wibom R, Tornell J, Jacobs HT, Larsson NG. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 2004;429:417-423.

26. Balaban RS, Nemoto S, Finkel T. Mitochondria, Oxidants, and aging. Cell 2005;120:483-495.