8 April 2016
Nicholas Stroustrup
Fontana Lab, Department of Systems Biology
Harvard Medical School
The aging process makes death increasingly likely, involving a random aspect that produces a wide distribution of lifespan even in homogeneous populations. This randomness emerges from a set of complex functional deficits that accumulate in each of us as we age, observed as changes in diverse molecules, cells, tissues, organs, and organ systems. While each such change can be studied separately, the randomness and integrative physiologic complexity of organismal aging makes it difficult identify the unique contribution made by any single change. Many interventions have been found to extend the lifespan of diverse species including invertebrates and mice, but it remains unclear which aspects of physiology must necessarily be altered to produce these increases in lifespan.
To study the stochastic aspect of aging, I developed an imaging platform dubbed "The Lifespan Machine" that can be used to collect high-precision mortality statistics in controlled laboratory conditions. Using this method, I found that interventions as diverse as changes in diet, temperature, exposure to oxidative stress, and disruption of genes including the heat shock factor hsf-1, the hypoxia-inducible factor hif-1, and the insulin/IGF-1 pathway components daf-2, age-1, and daf-16 all alter lifespan distributions through an apparent stretching or shrinking of time. This temporal scaling would appear to require that each intervention alters, to the same quantitative extent throughout adult life, all physiological determinants of the risk of death. In my talk, I will explore how an ostensible coordination among all causes of death might arise during metazoan aging, and discuss how the phenomena of temporal scaling can be exploited experimentally, to dissect the complex causal structure of aging.