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      Lifespan Extension in Long-Lived Vertebrates Rooted in Ecological Adaptation

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          Abstract

          Contemporary studies on aging and longevity have largely overlooked the role that adaptation plays in lifespan variation across species. Emerging evidence indicates that the genetic signals of extended lifespan may be maintained by natural selection, suggesting that longevity could be a product of organismal adaptation. The mechanisms of adaptation in long-lived animals are believed to account for the modification of physiological function. Here, we first review recent progress in comparative biology of long-lived animals, together with the emergence of adaptive genetic factors that control longevity and disease resistance. We then propose that hitchhiking of adaptive genetic changes is the basis for lifespan changes and suggest ways to test this evolutionary model. As individual adaptive or adaptation-linked mutations/substitutions generate specific forms of longevity effects, the cumulative beneficial effect is largely nonrandom and is indirectly favored by natural selection. We consider this concept in light of other proposed theories of aging and integrate these disparate ideas into an adaptive evolutionary model, highlighting strategies in decoding genetic factors of lifespan control.

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          Most cited references182

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          Aging: a theory based on free radical and radiation chemistry.

          D. Harman (1956)
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            Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics.

            Adaptation of cancer cells to their microenvironment is an important driving force in the clonal selection that leads to invasive and metastatic disease. O2 concentrations are markedly reduced in many human cancers compared with normal tissue, and a major mechanism mediating adaptive responses to reduced O2 availability (hypoxia) is the regulation of transcription by hypoxia-inducible factor 1 (HIF-1). This review summarizes the current state of knowledge regarding the molecular mechanisms by which HIF-1 contributes to cancer progression, focusing on (1) clinical data associating increased HIF-1 levels with patient mortality; (2) preclinical data linking HIF-1 activity with tumor growth; (3) molecular data linking specific HIF-1 target gene products to critical aspects of cancer biology and (4) pharmacological data showing anticancer effects of HIF-1 inhibitors in mouse models of human cancer.
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              Pleiotropy, Natural Selection, and the Evolution of Senescence

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                Author and article information

                Contributors
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                18 October 2021
                2021
                : 9
                : 704966
                Affiliations
                [1] 1CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology , Beijing, China
                [2] 2University of Chinese Academy of Sciences , Beijing, China
                [3] 3Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School , Boston, MA, United States
                Author notes

                Edited by: Alan A. Cohen, Université de Sherbrooke, Canada

                Reviewed by: Maarten Wensink, University of Southern Denmark, Denmark; Oldrich Tomasek, Academy of Sciences of the Czech Republic (ASCR), Czechia

                *Correspondence: Xuming Zhou, zhouxuming@ 123456ioz.ac.cn

                This article was submitted to Signaling, a section of the journal Frontiers in Cell and Developmental Biology

                Article
                10.3389/fcell.2021.704966
                8558438
                34733838
                69dc87d6-c84a-4760-b3ae-f4d28f095e39
                Copyright © 2021 Omotoso, Gladyshev and Zhou.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 May 2021
                : 02 September 2021
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 182, Pages: 15, Words: 14172
                Categories
                Cell and Developmental Biology
                Review

                longevity,adaptive-hitchhiking,natural selection,aging,evolution theory

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