Negligible senescence in the longest living rodent, the naked mole-rat: Insights from a successfully aging species

Department of Physiology and The Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA.
Journal of Comparative Physiology B (Impact Factor: 2.62). 06/2008; 178(4):439-45. DOI: 10.1007/s00360-007-0237-5
Source: PubMed


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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Available from: Rochelle Buffenstein, Mar 21, 2014
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    • "Biological age is the loss of functional capacity of a cell or organism over time; an organism's biological age is not always equal to its chronological age. Damage markers, including oxidation of proteins, lipids and nucleic acids, protein stability, telomere length, and telomerase activity, correlate with chronological age in many species (Campisi 1996; Turturro et al. 1999; Proctor and Kirkwood 2002; Butler et al. 2004; Philipp et al. 2005a, b, 2006; Buffenstein 2008; Pérez et al. 2009; Austad 2010). Species with long lifespans also exhibit lower levels of cellular damage than species with short lifespans (Philipp et al. 2005a, b, 2006; Ungvari et al. 2008; Pérez et al. 2009; Austad 2010). "
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    ABSTRACT: One of the biggest challenges to studying causes and effects of aging is identifying changes in cells that are related to senescence instead of simply the passing of chronological time. We investigated two populations of the longest living non-colonial metazoan, Arctica islandica, with lifespans that differed sixfolds. Of four investigated parameters (nucleic acid oxidation, protein oxidation, lipid oxidation, and protein instability), only nucleic acid oxidation increased with age and correlated with relative lifespan. Nucleic acid oxidation levels increased significantly faster and were significantly higher in the shorter-lived than the longer-lived population. In contrast, neither protein oxidation, lipid oxidation, nor protein stability changed over time. Protein resistance to unfolding stress when treated with urea was significantly lower overall in the shorter-lived population, and lipid peroxidation levels were higher in the longer-lived population. With the exception of nucleic acid oxidation, damage levels of A. islandica do not change with age, indicating excellent cellular maintenance in both populations. Since correlations between nucleic acid oxidation and age have also been shown previously in other organisms, and nucleic acid oxidation accumulation rate correlates with relative age in both investigated populations, nucleic acid oxidation may reflect intrinsic aging mechanisms.
    Age 10/2015; 37(5):9831. DOI:10.1007/s11357-015-9831-8 · 3.45 Impact Factor
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    • "For example, cave Myotis bats and Mexican free-tailed bats (both with maximum lifespan potential of 12 years) show lower protein carbonylation and ubiquitination in liver than mice, and their cells are more resistant to protein oxidation (Salmon et al., 2009; Shi et al., 2010). Mitochondria from bat heart also produce less hydrogen peroxide than those from shrew and white-footed mouse (Brunet-Rossinni, 2004), although the differences are less than the divergence in their maximum lifespans (Buffenstein et al., 2008). Hence, low methionine Figure 3. Distribution of Metabolites across the Organs (A) The overall pattern visualized on a heat map. "
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    ABSTRACT: Biological diversity among mammals is remarkable. Mammalian body weights range seven orders of magnitude and lifespans differ more than 100-fold among species. While genetic, dietary, and pharmacological interventions can be used to modulate these traits in model organisms, it is unknown how they are determined by natural selection. By profiling metabolites in brain, heart, kidney, and liver tissues of 26 mammalian species representing ten taxonomical orders, we report metabolite patterns characteristic of organs, lineages, and species longevity. Our data suggest different rates of metabolite divergence across organs and reveal patterns representing organ-specific functions and lineage-specific physiologies. We identified metabolites that correlated with species lifespan, some of which were previously implicated in longevity control. We also compared the results with metabolite changes in five long-lived mouse models and observed some similar patterns. Overall, this study describes adjustments of the mammalian metabolome according to lifespan, phylogeny, and organ and lineage specialization. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cell metabolism 08/2015; 22(2):332-43. DOI:10.1016/j.cmet.2015.07.005 · 17.57 Impact Factor
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    • "The NMR is the longest lived rodent known, with a maximum lifespan of 32 years—almost ten times longer than the mouse (Gorbunova, 2007). For at least 80% of their lives, NMRs show little signs of senescence, no age-related increase in mortality, and high fecundity (Buffenstein, 2008). In addition to such attenuated aging phenotypes, the NMR is also unusual for its pronounced cancer resistance (Liang et al., 2010), which, in part, has been explained by high molecular mass hyaluronan (Tian et al., 2013). "
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    ABSTRACT: Genome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation and mutation rate of 518 GM-associated genes in the naked mole rat (NMR), mouse, and human genomes. GM genes appeared to be strongly conserved, with copy number variation in only four genes. Interestingly, we found NMR to have a higher copy number of CEBPG, a regulator of DNA repair, and TINF2, a protector of telomere integrity. NMR, as well as human, was also found to have a lower rate of germline nucleotide substitution than the mouse. Together, the data suggest that the long-lived NMR, as well as human, has more robust GM than mouse and identifies new targets for the analysis of the exceptional longevity of the NMR.
    Aging cell 01/2015; 14(2). DOI:10.1111/acel.12314 · 6.34 Impact Factor
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