The Causes and Limits of Lifespan Extension

Meeting Summary: Given the massive complexity of biological systems, with built-in redundancies, adaptive capacity, and integration across micro and macro level organization, we ask can human aging be slowed or even reversed? We know that biological systems eventually age and fail; however, recent studies of short-lived species suggest that the pace of aging and how it manifests could be malleable, and importantly, that prolonged deterioration as a function of age may not be an inevitability. “Evolutionary loopholes” such as connections between growth, metabolism, and resilience, could potentially be exploited to delay aging or even reverse its effects. Achieving this requires understanding how evolving systems have incorporated regulatory switches that directly or indirectly influence longevity, and where these nodes occur on the multilevel network. Going from gene expression to intracellular signaling to tissue and organ level function, we hope to chart these interconnected systems and the regulatory nodes within. Our goal is to understand the impact of repair systems such as immunity and inflammation on these multi-tiered organizational domains, and how the interactions among systems influence frailty, resilience, and eventual biological failure. With these insights we can begin to ask questions about how nodes and system structures developed through evolution could be exploited, and whether any tradeoffs (for example between lifespan and healthspan) are expected. 

The working group “The causes and limits of lifespan” will bring together experts working on cellular processes, repair systems, disease, evolutionary biology and demography, and human social systems. We want to develop theory to explain the observed patterns of change with age that account for regulatory nodes associated with maintenance, functional integrity, and stasis, and those that might be harnessed to reverse the effects of age. The conceptual framework we propose to develop will have implications for systems biology, evolutionary biology, aging research, gerontology, and society.