The different paths to 100.

Many people believe that the older a person gets, the sicker he or she becomes. The result can be quite a pessimistic view of very old age. If this were true, most if not all centenarians would have significant disability. However, approximately 90% of centenarians in a population-based study were functionally independent at the average age of 92 y. Thus, to achieve extreme old age, a much more enabling point of view emerges: the older an individual gets, the healthier he or she has been. Centenarians thus have the potential to represent a model of relative resistance to age-related diseases and slower aging. Currently, 1 in every 10 000 persons in the United States is 100 y of age or older. This prevalence is quickly changing, however, and it is likely that most industrialized nations will soon experience twice that prevalence, or one centenarian per 5000 persons. The ability to survive to extreme old age appears to be the result of a complex combination of genetics, environment, lifestyle, and luck. Understanding the genetics of the very old, and identifying the molecular drivers of longevity (or of mortality), is a potentially powerful approach to discovering and targeting the pathways mediating aging and disease susceptibility and developing preventive and therapeutic agents that will allow more of the population to age in good health.