Call for papers: aging versus disease.

Along-lasting and extensive literature has conceptualized the aging process as a universal and unavoidable process of physiological decline that is associated with increased global vulnerability to diseases and death. On the contrary, diseases occur in some individuals and not in others, are connected with specifi c exogenous risk factors and pathophysiological mechanisms, and may not increase the risk for death. These characteristics make diseases preventable ( 1 ). As a consequence of this view, efforts to understand aging have emphasized the need to distinguish aging from disease. Indeed, the need to study aging separate from diseases was a fundamental premise of the fi rst large-scale study of aging, the Baltimore Longitudinal Study on Aging ( 2 ), which required all participants to undergo a careful physical examination to exclude diseases as possible causes of the observed age-related changes. Beyond theoretical models, chronic diseases accumulate with aging, and together, aging and diseases show mutual interactions in causing deterioration in health, physical and cognitive function, and premature death. Thus, it remains unclear as to whether we can truly distinguish the secondary effects of disease from those of aging per se. In animal models of aging, researchers have begun to characterize aging processes by manipulating diet and genes to change life span ( 3 ), although the effect of modifying these genes on disease susceptibility has not been fully explored. Intermediate phenotypes to longevity have also been examined using measures of physical function. Motility in worms ( 4 ) and gait speed in humans ( 5 ) are perhaps the strongest predictors of mortality even in individuals who are genetically identical. Thus, mobility can be considered to be a proxy phenotype for aging, a sort of universal parameter that can be used to relate the rate of aging across multiple species. Although the pathology of worms has not been studied in depth, it is unlikely that worms suffer from the extreme heterogeneous patterns of disease that contribute to the loss of mobility in humans. Hence, understanding what aspects of mobility loss in humans are due to universal aging processes independent of disease represents a true challenge.