Understanding mechanisms underlying longevity, and endeavor towards the specific goals of alleviating frailty in old age, require a comprehensive approach that considers the various theoretical and experimental approaches, as well as compiling the data on humans. This logistic has underlined the program of the conference, and is reflected in the present special issue. Considerable volume of data now point to distinct genes that are associated with exceptional longevity in humans, as reflected from the articles in this volume. However, this symposium also highlighted non-genetic effects, including physical, mental and social activities, and elucidate the relevant underlying mechanisms. The symposium focused on understanding the basis of human longevity coupled to extended health-span and function into old age.