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The landscape of longevity across phylogeny

View ORCID ProfileDmitriy I. Podolskiy, View ORCID ProfileAndrei Avanesov, View ORCID ProfileAlexander Tyshkovskiy, Emily Porter, View ORCID ProfileMichael Petrascheck, View ORCID ProfileMatt Kaeberlein, Vadim N. Gladyshev
doi: https://doi.org/10.1101/2020.03.17.995993
Dmitriy I. Podolskiy
1Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
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  • ORCID record for Dmitriy I. Podolskiy
Andrei Avanesov
1Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
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Alexander Tyshkovskiy
1Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
2Center for Data-Intensive Biomedicine and Biotechnology, Skolkovo Institute of Science and Technology, Moscow, Russia
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Emily Porter
1Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
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Michael Petrascheck
3The Scripps Research Institute, La Jolla, CA 92037, USA
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Matt Kaeberlein
4Department of Pathology, University of Washington, Seattle, WA 98195, USA
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Vadim N. Gladyshev
1Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
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  • For correspondence: vgladyshev@rics.bwh.harvard.edu
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Abstract

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.

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Posted March 18, 2020.
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The landscape of longevity across phylogeny
Dmitriy I. Podolskiy, Andrei Avanesov, Alexander Tyshkovskiy, Emily Porter, Michael Petrascheck, Matt Kaeberlein, Vadim N. Gladyshev
bioRxiv 2020.03.17.995993; doi: https://doi.org/10.1101/2020.03.17.995993
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The landscape of longevity across phylogeny
Dmitriy I. Podolskiy, Andrei Avanesov, Alexander Tyshkovskiy, Emily Porter, Michael Petrascheck, Matt Kaeberlein, Vadim N. Gladyshev
bioRxiv 2020.03.17.995993; doi: https://doi.org/10.1101/2020.03.17.995993

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