RT Journal Article
SR Electronic
T1 The landscape of longevity across phylogeny
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.17.995993
DO 10.1101/2020.03.17.995993
A1 Dmitriy I. Podolskiy
A1 Andrei Avanesov
A1 Alexander Tyshkovskiy
A1 Emily Porter
A1 Michael Petrascheck
A1 Matt Kaeberlein
A1 Vadim N. Gladyshev
YR 2020
UL http://biorxiv.org/content/early/2020/03/18/2020.03.17.995993.abstract
AB Lifespan of model organisms can be extended by genetic, dietary and pharmacological interventions, but these effects may be negated by other factors. To understand robustness of longevity interventions within and across species, we analyzed age-dependent mortality of yeast, fruit flies, nematodes and mice subjected to thousands of genetic, pharmacological or dietary interventions, and applied the principles learned to other organisms. Across phylogeny, the accessible space of lifespan distribution functions, the “landscape of longevity”, has a distinct structure of a fiber bundle, with individual fibers given by Strehler-Mildvan degeneracy manifolds. Within species, most interventions perturb parameters of survival curves along particular degeneracy manifolds. Transitions across manifolds are difficult to achieve, but they may lead to robust lifespan-modulating effects. Analyses of intraspecific degeneracy manifolds revealed soft bounds on achievable longevity. For humans, this bound is ∼138 years.