Molecular gerontology. Bridging the simple and the complex

It is clear, both empirically and theoretically, that the mechanisms of aging are multiple and complex. Nevertheless, single gene mutations and simple interventions such as calorie restriction have broad effects on the senescent phenotype. The major challenge is to unite highly reductionist analysis of molecular components with integrative model systems that can "put it all together." Two themes are developed. In the first, biochemical models are described that show how the network concept of cellular aging can be used to integrate multiple biochemical mechanisms that contribute to cellular instability. In the second theme, the role of intrinsic developmental chance is examined as a major factor contributing, in addition to genes and environment, to the divergence of the senescent phenotype. The implications of these themes for research strategies in molecular gerontology are discussed.