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      Naked mole-rat mortality rates defy Gompertzian laws by not increasing with age

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          Abstract

          The longest-lived rodent, the naked mole-rat ( Heterocephalus glaber), has a reported maximum lifespan of >30 years and exhibits delayed and/or attenuated age-associated physiological declines. We questioned whether these mouse-sized, eusocial rodents conform to Gompertzian mortality laws by experiencing an exponentially increasing risk of death as they get older. We compiled and analyzed a large compendium of historical naked mole-rat lifespan data with >3000 data points. Kaplan-Meier analyses revealed a substantial portion of the population to have survived at 30 years of age. Moreover, unlike all other mammals studied to date, and regardless of sex or breeding-status, the age-specific hazard of mortality did not increase with age, even at ages 25-fold past their time to reproductive maturity. This absence of hazard increase with age, in defiance of Gompertz’s law, uniquely identifies the naked mole-rat as a non-aging mammal, confirming its status as an exceptional model for biogerontology.

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          The moulding of senescence by natural selection.

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            Diversity of ageing across the tree of life.

            Evolution drives, and is driven by, demography. A genotype moulds its phenotype's age patterns of mortality and fertility in an environment; these two patterns in turn determine the genotype's fitness in that environment. Hence, to understand the evolution of ageing, age patterns of mortality and reproduction need to be compared for species across the tree of life. However, few studies have done so and only for a limited range of taxa. Here we contrast standardized patterns over age for 11 mammals, 12 other vertebrates, 10 invertebrates, 12 vascular plants and a green alga. Although it has been predicted that evolution should inevitably lead to increasing mortality and declining fertility with age after maturity, there is great variation among these species, including increasing, constant, decreasing, humped and bowed trajectories for both long- and short-lived species. This diversity challenges theoreticians to develop broader perspectives on the evolution of ageing and empiricists to study the demography of more species.
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              Negligible senescence in the longest living rodent, the naked mole-rat: insights from a successfully aging species.

              Aging refers to a gradual deterioration in function that, over time, leads to increased mortality risk, and declining fertility. This pervasive process occurs in almost all organisms, although some long-lived trees and cold water inhabitants reportedly show insignificant aging. Negligible senescence is characterized by attenuated age-related change in reproductive and physiological functions, as well as no observable age-related gradual increase in mortality rate. It was questioned whether the longest living rodent, the naked mole-rat, met these three strict criteria. Naked mole-rats live in captivity for more than 28.3 years, approximately 9 times longer than similar-sized mice. They maintain body composition from 2 to 24 years, and show only slight age-related changes in all physiological and morphological characteristics studied to date. Surprisingly breeding females show no decline in fertility even when well into their third decade of life. Moreover, these animals have never been observed to develop any spontaneous neoplasm. As such they do not show the typical age-associated acceleration in mortality risk that characterizes every other known mammalian species and may therefore be the first reported mammal showing negligible senescence over the majority of their long lifespan. Clearly physiological and biochemical processes in this species have evolved to dramatically extend healthy lifespan. The challenge that lies ahead is to understand what these mechanisms are.
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                Author and article information

                Contributors
                Role: Reviewing Editor
                Journal
                eLife
                Elife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                24 January 2018
                2018
                : 7
                Affiliations
                [1 ]Calico Life Sciences LLC South San FranciscoUnited States
                University of California, Irvine United States
                University of California, Irvine United States
                Article
                31157
                10.7554/eLife.31157
                5783610
                29364116
                1109848f-6d58-4c67-994d-f1791e77d05e
                © 2017, Ruby et al

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                Product
                Funding
                This study was funded by Calico Life Sciences LLC.
                Categories
                Research Article
                Ecology
                Custom metadata
                Unlike all other mammals studied to date, the age-specific risk of mortality for naked mole-rats did not increase over decades of life, identifying this species as a non-aging mammal.

                Life sciences
                naked mole-rat,gompertz,aging,heterocephalus glaber,other
                Life sciences
                naked mole-rat, gompertz, aging, heterocephalus glaber, other

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