حفاظت از توانایی های شناختی و عملکردی به عنوان نشانگر طول عمر

Longevity is a complex biological process for which the phenotypes have not been established. Preservation of cognitive and physical function may be important and preservation of these functions is, in part, inherited. We investigated the relation between rate of change in cognitive and functional abilities in probands and risk of death in their siblings. Probands were classified as showing no decline, slow, medium, or rapid rate of decline, based on the slope of change in cognitive and physical/functional factors over three or more assessments. Siblings of probands who did not decline on measures of memory, visuospatial/cognitive function or ADL skills were approximately half as likely to die as siblings of probands who had the most rapid decline. The reduction in risk of death in siblings of probands who did not decline in was primarily observed among siblings of probands who were older than 75 years, suggesting that genetic influences on life span may be greater at older ages. There was no association between probands’ rate of change in language, IADL skills, upper or lower extremity mobility and risk of death in siblings. The results of the present study identify phenotypes associated with preserved cognitive and functional abilities which may serve as markers for longevity.

The heritability of longevity has been estimated from investigations of human twins, isolated and founder populations [11]. Monozygotic twins are twice as likely to be concordant for total years of life as dizygotic twins [23]. Overall, heritability of life span is approximately 20–30% [23], [33] and [40]. Genetic influences on life span appear to be greater at extreme old age. Siblings of centenarians were four times as likely to live beyond 85 years as were siblings of individuals who did not survive past 73 years [43], and first degree relatives of individuals who lived beyond 95 years were twice as likely to survive to the same age as were relatives of controls [22] and [28]. The biological mechanisms mediating longevity are still unknown. Findings from centenarian and twin studies suggest that preservation of cognitive and physical function is important. In the New England Centenarian study, individuals who lived to extreme old age were found to have been healthy and independent for most of their lives [24]. Offspring of centenarians have favorable lipid profiles and lower relative prevalence of heart disease, hypertension and diabetes [1] and [12]. Genetic influences on general and specific cognitive function are substantial in studies of human twins [13], [14], [37], [38], [42], [44] and [56]. About half the variance in cognitive function can be accounted for by genetic differences [42]. McClearn et al. [37] studied the heritability of cognitive function in Swedish twins 80 years of age and older and showed that genetic influences on cognitive performance continue into old age. Apolipoprotein E (APOE) has been proposed as one candidate gene consistently associated with longevity and memory function [31], [34], [36], [45] and [50]. Data concerning the heritability of physical and functional ability are more limited, but support the hypothesis that genetic influences contribute to individual differences in function and that preservation of physical and functional ability may be associated with longevity [8], [10] and [16]. Genetic factors may influence both the level as well as the rate of change in cognitive and physical functions [41]. Whether or not the genes that influence cognitive and physical function at a given age are the same as those that influence the rate of change in these functions remains unknown. In this study, preservation of cognitive and functional abilities was investigated in relation to survival in family members. We also investigated the relation between survival in families and the rate of change in cognitive and functional abilities in younger and older probands and across three ethnic groups.