The science of healthy aging: genes, milieu, and chance.

Healthy aging and longevity depend on successful and dynamic interactions among biological, psychological, and environmental factors. Biological aging occurs mainly during the period of survival beyond the evolutionarily required essential lifespan (ELS). Natural selection processes for survival and successful reproduction have selected for a range of genetically determined ELS-assuring maintenance and repair systems (MRSs). The progressive failure of MRSs, and the consequent accumulation of molecular heterogeneity and damage, underlie the biological basis of aging, age-related diseases, and eventual death. However, the genetic processes of MRSs operate in a complex hierarchy of factors which range from intracellular molecular factors to physiological, psychological, environmental, and other stochastic factors, including chance. This view also facilitates setting up a framework for understanding, researching, and developing effective and realistic strategies for aging intervention, prevention, and therapies. Manipulating genes and the milieu in which genes and gene products operate opens up novel possibilities of aging intervention and prevention. Gene therapy, stem cells, and modulation through functional foods, nutriceuticals, cosmeceuticals and lifestyle alterations, including mild stress-induced hormesis, are examples of such strategies at various levels of development and practice.