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Accelerated Aging: Human Progeroid Syndromes - Unifying Concepts

age developmental physiological genetic damage normal cellular genetic

If segmental progeroid syndromes are informative with respect to normal aging, what have they revealed thus far? These diseases support the view that aging results from the accumulation of damage to cellular components caused by biochemical errors and/or deleterious agents over a lifetime—and they undermine the idea of a genetic program for aging. By this reasoning, the rare occurrence of metabolic errors and the appropriate cellular maintenance processes in normal individuals cause damage to accumulate slowly, but this damage eventually causes enough harm to result in multiple aging characteristics. Specific types of errors are amplified in progeroid syndromes, resulting in increased cellular damage and certain premature aging characteristics. Interestingly, several progeroid syndromes show genetic instability (chromosomal aberrations and/or telomere shortening), suggesting connections between DNA damage and aging characteristics. Clearly, genetic damage accumulates even during normal life span and is directly related to increased cancer frequency with age. Although the relationship between DNA damage and other signs of normal aging is unclear, accumulation of oxidative damage to DNA, proteins, and membranes has been strongly implicated in many features of normal aging. Even if the biochemical defects in segmental progeroid syndromes do not directly imitate the types of mistakes made during normal aging, the cellular outcomes are probably similar—loss of cell cycle control (cancer), decrease in cell function, cellular senescence, and cell death (apoptosis). In turn, the accumulation of these cellular effects manifests itself in the physiological degeneration that we recognize as human aging.

DAVID K. ORREN

See also CELLULAR AGING; DNA DAMAGE AND REPAIR; GENETICS; LONGEVITY: SELECTION; MOLECULAR BIOLOGY OF AGING; PHYSIOLOGICAL CHANGES.

BIBLIOGRAPHY

ARKING, R. "Genetic Determinants of Longevity." In Biology of Aging, 2d ed. Edited by R. Arking. Sunderland, Mass.: Sinauer Associates, 1998. Pages 251–309.

BLACKBURN, E. H. "Telomere States and Cell Fates." Nature 408 (2000): 53–56.

CAPONE, G. T. "Down Syndrome: Advances in Molecular Biology and the Neurosciences." Developmental and Behavioral Pediatrics 22, no. 1 (2001): 40–59.

DYER, C. A. E., and SINCLAIR, A. J. "The Premature Aging Syndromes: Insights into the Ageing Process." Age and Ageing 27 (1998): 73–80.

FINKEL, T., and HOLBROOK, N. J. "Oxidants, Oxidative Stress, and the Biology of Aging." Nature 408 (2000): 239–247.

GOTO, M. "Hierarchical Deterioration of Body Systems in Werner's Syndrome: Implications for Normal Aging." Mechanisms of Ageing and Development 98 (1997): 239–254.

HANAWALT, P. C. "The Bases for Cockayne Syndrome." Nature 405 (2000): 415–416.

MARTIN, G. M. "Genetic Syndromes in Man with Potential Relevance to the Pathobiology of Aging." In Genetic Effects on Aging. Edited by . Bergsma and D. E. Harrison. New York: Alan R. Liss, 1978. Pages 5–39.

MARTIN, G. M., and OSHIMA, J. "Lessons from Human Progeroid Syndromes." Nature 408 (2000): 263–266.

OSHIMA, J. "The Werner Syndrome Protein: An Update." Bioessays 22, no. 10 (2000): 894–901.

RAPIN, I.; LINDENBAUM, Y.; DICKSON, D. W.; KRAEMER, K. H.; and ROBINS, J. H. "Cockayne Syndrome and Xeroderma Pigmentosum." Neurology 55 (2000): 1442–1449.

REEVES, R. H.; BAXTER, L. L.; and RICHTSMEIER, J. T. "Too Much of a Good Thing: Mechanisms of Gene Action in Down Syndrome." Trends in Genetics 17, no. 2 (2001): 83–88.

SARKAR, P. K., and SHINTON, R. A. "Hutchinson-Guilford Progeria Syndrome." Postgraduate Medical Journal 77 (2001): 312–317.

SHILOH, Y. "Ataxia-Telangiectasia and the Nijmegen Breakage Syndrome: Related Disorders but Genes Apart." Annual Review of Genetics 31 (1997): 635–662.

VAN GOOL, A. J.; VAN DER HORST, G. T. J.; CITTERIO, E.; and HOEIJMAKERS, J. H. J. "Cockayne Syndrome: Defective Repair or Transcription." The EMBO Journal 16, no. 14 (1997): 4155–4162.

YU, C.; OSHIMA, J.; FU, Y.; WIJSMAN, E. M.; HISAMA, F.; ALISCH, R.; MATTHEWS, S.; NAKURA, J.; MIKI, T.; OUAIS, S.; MARTIN, G. M.; MULLIGAN, J.; and SCHELLENBERG, G. D. "Positional Cloning of the Werner's Syndrome Gene." Science 272 (1996): 258–262.

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