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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: 2.53). 06/2008; 178(4):439-45. DOI: 10.1007/s00360-007-0237-5
Source: PubMed

ABSTRACT 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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    • "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 · 5.94 Impact Factor
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    • "Considering that NMRs are extremely resilient to a variety of stressors and they are considered a model of successful aging [19], the available data strongly suggest that an improved proteostasis network may be necessary for the maintenance of longer health and life in NMRs. "
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    ABSTRACT: Our previous studies have shown that the liver from Naked Mole Rats (NMRs), a long-lived rodent, has increased proteasome activity and lower levels of protein ubiquitination compared to mice. This suggests that protein quality control might play a role in assuring species longevity. To determine whether enhanced proteostasis is a common mechanism in the evolution of other long-lived species, here we evaluated the major players in protein quality control including autophagy, proteasome activity, and heat shock proteins (HSPs), using skin fibroblasts from three phylogenetically-distinct pairs of short- and long-lived mammals: rodents, marsupials, and bats. Our results indicate that in all cases, macroautophagy was significantly enhanced in the longer-lived species, both at basal level and after induction by serum starvation. Similarly, basal levels of most HSPs were elevated in all the longer-lived species. Proteasome activity was found to be increased in the long-lived rodent and marsupial but not in bats. These observations suggest that long-lived species may have superior mechanisms to ensure protein quality, and support the idea that protein homeostasis might play an important role in promoting longevity. Copyright © 2015. Published by Elsevier Inc.
    Biochemical and Biophysical Research Communications 01/2015; 457(4). DOI:10.1016/j.bbrc.2015.01.046 · 2.28 Impact Factor
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    • "The naked mole rat (NMR; Heterocephalus glaber) is a long-lived subterranean rodent native to the Horn of Africa. It can not only live to 430 years, making it the longest-lived rodent, but is also extremely resistant to neoplasia (Buffenstein, 2008; Tian et al., 2013), and as a result is an ideal model for research on longevity, cancer and disease resistance. The NMR genome was sequenced at the BGI in 2011 to 92-fold coverage with a contig N50 of 19.3 kb and scaffold N50 of 1.6 Mb (Kim et al., 2011). "
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    ABSTRACT: Motivation: The naked mole rat (Heterocephalus glaber) is an exceptionally long-lived and cancer-resistant rodent native to East Africa. Although its genome was previously sequenced, here we report a new assembly sequenced by us with substantially higher N50 values for scaffolds and contigs. Results: We analyzed the annotation of this new improved assembly and identified candidate genomic adaptations which may have contributed to the evolution of the naked mole rat’s extraordinary traits, including in regions of p53, and the hyaluronan receptors CD44 and HMMR (RHAMM). Furthermore, we developed a freely available web portal, the Naked Mole Rat Genome Resource (http://www.naked-mole-rat.org), featuring the data and results of our analysis, to assist researchers interested in the genome and genes of the naked mole rat, and also to facilitate further studies on this fascinating species. Availability and implementation: The Naked Mole Rat Genome Resource is freely available online at http://www.naked-mole-rat.org. This resource is open source and the source code is available at https://github.com/maglab/naked-mole-rat-portal. Contact: jp@senescence.info
    Bioinformatics 08/2014; 30(24). DOI:10.1093/bioinformatics/btu579 · 4.62 Impact Factor
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