Accelerated Aging: Human Progeroid Syndromes
Unifying Concepts
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.
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ACTIVITIES OF DAILY LIVING
See FUNCTIONAL ABILITY
Additional topics
Medicine EncyclopediaAging Healthy - Part 1Accelerated Aging: Human Progeroid Syndromes - Progeroid Syndromes As Models Of Aging, Down Syndrome, Adult Progeria (werner Syndrome), Progeria (hutchinson-gilford Syndrome)