Resveralogues: From Novel Ageing Mechanisms to New Therapies?

For much of the 20th century the ageing process was thought to be the result of the interplay of many different biological processes, each with relatively small effects on organismal lifespan. However, this model is no longer tenable. Rather it seems a few biological mechanisms, including nutrient sensing, telomere attrition and cellular senescence, mediate large effects on health and longevity. Biogerontology may have suffered from initial delusions of complexity. However, we argue that it is premature to assume either that the list of biological processes influencing lifespan is now comprehensive or that these mechanisms act independently of each other. A case in point is provided by recent work linking together changes in RNA splicing with advancing age and the ability of polyphenolics based on resveratrol to reverse replicative senescence. In this opinion piece, we propose a novel model in which the factors regulating splice restriction and those controlling cell senescence intersect across chronological and divisional time, giving rise to senescent and growing cells with more diverse properties than previously thought. We also consider therapeutic opportunities and potential problems in the light of this revised conceptual understanding of human cell senescence and ageing.