Molecular Mechanisms of Aging

Topics: Senescence, Gerontology, Aging Pages: 14 (4995 words) Published: February 5, 2013
The Real Fountain of Youth: Modern conceptions of ageing and proposed methods of lifespan extension.

Mitchell S. Kirby
121 Little Hall
Princeton University
Princeton, NJ 08544

Advisor: Dr. Leon Rosenberg

May 4th, 2010

This paper represents my own work in accordance with University regulations.

The mechanisms that regulate cellular senescence, organismal ageing, and species-specific lifespan depend on a synergy of pathways that are multifactorial and extremely complex, though not yet completely understood. Recently, the development of new molecular techniques has elucidated, at least in part, the primary pathways involved in ageing. In parallel with the search to uncover the factors that control ageing is the endeavor to discover methods of extending lifespan, in hopes of living both youthfully and longer. Specifically, caloric restriction regimens and rapamycin feeding have been shown to increase lifespan in a variety of species, though other methods will be discussed as well. The illumination of ageing mechanisms side-by-side with means of extending lifespan provides a foundation from which to determine a complete multidimensional map of ageing pathways and the place of various lifespan extension methods within it. Furthermore, this information acts as a stepping stone from which to evaluate the feasibility of potential lifespan extenders and to grant recommendations for a dietary regimen bestowing a long and healthy life to its patrons. Specific Aims

The Fountain of Youth, a mystical spring that bestows youth and immortality to those who drink from it, captured the attention of Spanish Conquistadors exploring the American terrain. Though many centuries have passed, the fascination with delaying ageing and living forever has never dwindled. Today, scientists serve as contemporary conquistadors, searching for the real Fountain of Youth in the form of pharmaceuticals and health regimens that will increase lifespan, delay ageing, and decrease the onset of age-associated diseases. Before successful lifespan extension models can be implemented in humans, the following questions must be answered (Sander et al., 2008): What are the signs of human ageing? Is there a limit to the length of human life? Why does ageing occur? What are the genetic factors involved in ageing? To what extent do environmental factors influence ageing? The current study seeks to address these questions by analyzing the various theories of ageing, and relating them to each other and to means of lifespan extension. Once the current understanding of the molecular basis of ageing is established, it will be used to assess the feasibility of methodologies thought to delay death and to suggest eating habits associated with increased lifespan and healthspan. Background and Significance

What is Ageing?
Before attempting to uncover the mechanisms that guide the process of ageing, it is essential to understand what ageing actually is. Most generally, ageing is the accumulation of changes in an organism that over time leads to an increase in stress vulnerability and to a decrease in physiological homeostasis (Bowen and Atwood, 2004; Sander et al, 2008). Though the concept of age is commonly regarded as the time an organism has been alive, some believe a better functional measure is a determination of the amount of time an organism has until its death (Birren and Cunningham, 1985).

Ageing on an organismal scale is the result of the accumulation of senescence on a cellular level. Replicative senescence, or the loss of the cellular ability to divide, was first described by Dr. Leonard Hayflick upon discovering that human fibroblasts can undergo only a finite number of cell divisions (Hayflick and Moorehead, 1961). Interestingly, as the cells approached their replicative limit, their cellular structure deteriorated, they failed to produce enzymes or energy, and they accumulated a great deal of waste, all features...

References: Addabbo, F.M. Montagnani, M.S. Goligorsky. “Mitochondria and reactive oxygen species.” Hypertension 53(2009): 885-92. Print
Baur, J
Bell, D. R., and G. Van Zant. "Stem Cells, Aging, and Cancer: Inevitabilities and Outcomes." Oncogene 23.43 REV. ISS. 6 (2004): 7290-6. Print.
Ben-Porath, I., and R. A. Weinberg. "When Cells Get Stressed: An Integrative View of Cellular Senescence." Journal of Clinical Investigation 113.1 (2004): 8-13. Print.
Birren, J.E. and W.R Cunningham. “Research on the psychology of aging: principles, concepts, and theory.” Handbook of the Psychology of Aging (1985).
Blasco, M. A. "Mice with Bad Ends: Mouse Models for the Study of Telomeres and Telomerase in Cancer and Aging." EMBO Journal 24.6 (2005): 1095-103. Print.
Boerrigter, M. E. T. I., J. Y. Wei, and J. Vijg. "Induction and Repair of Benzo[a]Pyrene-DNA Adducts in C57BL/6 and BALB/c Mice: Association with Aging and Longevity." Mechanisms of ageing and development 82.1 (1995): 31-50. Print.
Bowen, R.L. and C.S. Atwood. "Living and dying for sex. A theory of aging based on the modulation of cell cycle signaling by reproductive hormones.". Gerontology 50 (2004): 265–90.Print
Chakhparonian, M., and R
Colman, R. J., et al. "Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys." Science 325.5937 (2009): 201-4. Print.
Cox, L. S., and J. A. Mattison. "Increasing Longevity through Caloric Restriction Or Rapamycin Feeding in Mammals: Common Mechanisms for Common Outcomes?" Aging Cell 8.5 (2009): 607-13. Print.
Dilman, V. M., S. Y. Revskoy, and A. G. Golubev. "Neuroendocrine-Ontogenetic Mechanism of Aging: Toward an Integrated Theory of Aging." International review of neurobiology 28 (1986): 89-156.
Easton, J. B., and P. J. Houghton. "MTOR and Cancer Therapy." Oncogene 25.48 (2006): 6436-46. Print.
Fowler, C. G., et al. "Auditory Function in Rhesus Monkeys: Effects of Aging and Caloric Restriction in the Wisconsin Monkeys Five Years Later." Hearing research 261.1-2 (2010): 75-81. Print.
Goodman, M., et al. "Molecular Evolution in the Descent of Man." Nature 233.5322 (1971): 604-13. Print.
Harman, D. “Aging: A theory based on free radical and radiation chemistry.” Journal of Gerontology 11(1956): 145-147.
Harrison, D
Hart, R. W., and R. B. Setlow. "Correlation between Deoxyribonucleic Acid Excision Repair and Life Span in a Number of Mammalian Species." Proceedings of the National Academy of Sciences of the United States of America 71.6 (1974): 2169-73. Print.
Hayflick L & Moorhead P S. The serial cultivation of human diploid cell strains. Exp. Cell Res. 25:585-621, 1961.
Holloszy, J. O., and L. Fontana. "Caloric Restriction in Humans." Experimental gerontology 42.8 (2007): 709-12. Print.
Krtolica, A., et al. "Quantification of Epithelial Cells in Coculture with Fibroblasts by Fluorescence Image Analysis." Cytometry 49.2 (2002): 73-82. Print.
Laird, R. A., and T. N. Sherratt. "The Evolution of Senescence in Multi-Component Systems." BioSystems 99.2 (2010): 130-9. Print.
Marques, F. Z., M. A. Markus, and B. J. Morris. "The Molecular Basis of Longevity, and Clinical Implications." Maturitas 65.2 (2010): 87-91. Print.
Messaoudi, I., et al. "Optimal Window of Caloric Restriction Onset Limits its Beneficial Impact on T-Cell Senescence in Primates." Aging Cell 7.6 (2008): 908-19. Print.
Mullaart, E., et al. "DNA Damage Metabolism and Aging." Mutation Research - DNAging Genetic Instability and Aging 237.5-6 (1990): 189-210. Print.
Nakamura, K. -I, et al. "Telomeric DNA Length in Cerebral Gray and White Matter is Associated with Longevity in Individuals Aged 70 Years Or Older." Experimental gerontology 42.10 (2007): 944-50. Print.
Niedernhofer, L. J., et al. "A New Progeroid Syndrome Reveals that Genotoxic Stress Suppresses the Somatotroph Axis." Nature 444.7122 (2006): 1038-43. Print.
Sacher, G. A. "Evolutionary Theory in Gerontology." Perspectives in biology and medicine 25.3 (1982): 339-53. Print.
Sander, M., et al. "Aging-from Molecules to Populations." Mechanisms of ageing and development 129.10 (2008): 614-23. Print.
Setlow, R.B., Carrier, W.L. “The disappearance of thymine dimers from DNA: an error-correcting mechanism.” Proc. Natl. Acd. Sci. U.S.A. 51(1964): 226-231.
Shawi, M., and C. Autexier. "Telomerase, Senescence and Ageing." Mechanisms of ageing and development 129.1-2 (2008): 3-10. Print.
Shay, J. W., and S. Bacchetti. "A Survey of Telomerase Activity in Human Cancer." European Journal of Cancer Part A 33.5 (1997): 787-91. Print.
Sohal, R. S., and W. C. Orr. "Relationship between Antioxidants, Prooxidants, and the Aging Process." Annals of the New York Academy of Sciences 663 (1992): 74-84. Print.
Suh, Y., and J. Vijg. "Maintaining Genetic Integrity in Aging: A Zero Sum Game." Antioxidants and Redox Signaling 8.3-4 (2006): 559-71. Print.
Szliard, L. “On the nature of the aging process” Proc. Natl. Acad. Sci. U.S.A. 45(1959): 30-45.
Valdes, A
Vijg, J. "The Role of DNA Damage and Repair in Aging: New Approaches to an Old Problem." Mechanisms of ageing and development 129.7-8 (2008): 498-502. Print.
Wilson III, D. M., V. A. Bohr, and P. J. McKinnon. "DNA Damage, DNA Repair, Ageing and Age-Related Disease." Mechanisms of ageing and development 129.7-8 (2008): 349-52. Print.
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