Is achieving extreme old age worthwhile the centenarian phenotype

Average life expectancy has markedly increased over the past century. In 1900 average life expectancy was 46 years and in the United States it is currently almost 79 years. The age 85+ group is the fastest growing segment of our population and within that group, the number of centenarians is growing even faster. Whether mortality declines have been accompanied by health improvements among the elderly has been a matter of debate. Some authors have suggested that mortality declines have led to increased prevalence of frailty among older survivors because treatment of existing diseases simply postpones death to older ages (Gruenberg, 1977; Kramer, 1983; Olshansky and Ault, 1986), while others suggest that mortality declines have led to a compression of morbidity (Fries, 1980). Early US evidence from the 1970s was generally consistent with the idea that health among the elderly had deteriorated (Crimmins and Ingegneri, 1993; Verbrugge, 1984), while more recent evidence provides a somewhat more optimistic view (Freedman and Soldo, 1994; Manton et al., 1997). Changes in disability prevalence over time, however, have varied by type and severity and by the data source used for trend analyses (Waidmann and Manton, 1998).

Centenarians studied by Hitt et al. appear to fit the pattern of postponement of disability to very advanced ages. In a population-based sample, it was observed that 90% of centenarians were independently functioning at age 92 (Hitt et al., 1999). Most subjects experienced a decline in their cognitive function only in the last three to five years of their lives (Perls, 1997; Silver et al., 1998). Upon further examination of the ages of onset for ten common age-associated diseases (hypertension, heart disease, diabetes, stroke, non-skin cancer, skin cancer, osteoporosis, thyroid condition, Parkinson's disease, chronic obstructive pulmonary disease and cataracts) among 424 centenarians (323 males and 101 females), the subjects were noted to fit into three morbidity profiles: ''survivors,'' ''delayers'' and ''escapers'' (Evert et al., 2003). Survivors, individuals who were diagnosed with age-related illness prior to age 80, accounted for 24% of the male and 43% of the female centenarians (p — 0.0009). Delayers, individuals who delayed the onset of age-related diseases until at least age 80, accounted for 44% of the male and 42% of female centenarians. Escapers, individuals who attained the hundredth year of life without the diagnosis of an age-related disease, accounted for 32% of the male and 15% of the female centenarians (p — 0.0003). In this study, the prevalence of coronary heart disease was 46% for men with a median age of diagnosis of 92 years and 39% for women with a median age of diagnosis of 93 years (Evert et al., 2003). The finding of a substantial number of centenarians fitting a ''survivor'' profile may be inconsistent with the compression of morbidity hypothesis. That most centenarians appear to be functionally independent through their early nineties suggests the possibility that "survivors" and "delayers" are better able to cope with illnesses and remain functionally independent. Thus, in the case of centenarians, it may be more accurate to note a compression of disability rather than morbidity. This is not the case, as would be expected, with illnesses associated with high mortality risks. When examining only the most lethal diseases of the elderly, including heart disease, non-skin cancer, and stroke, 87% of males and 83% of females delayed or escaped these diseases.

These results suggest that there may be multiple routes to achieving exceptional longevity and that there are gender differences according to which route is taken. These routes represent different phenotypes and thus likely different genotypes of centenarians. For example, differential coping abilities could be due to varying degrees of genetic homeostasis. If so, then what are the genetic (homeostatic) mechanisms involved in this (e.g. heterozygosity or dominance?). The identification of three subtypes of centenarians, Survivors, Delayers, and Escapers, provides direction for future study into factors that determine exceptional longevity (Evert et al., 2003).

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