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Mole Rats and Aging
Posted on: December 29, 2011

Naked mole rats (NMRs; Heterocephalus glaber) are the longest-living rodents known, with a maximum lifespan of 30 years – 5 times longer than expected on the basis of body size. These highly social mouse-sized rodents, naturally found in subterranean burrows in the arid and semiarid regions of the horn of Africa, are commonly used in behavioral, neurological, and ecophysiological research. Very old NMRs (>28 years), like humans, show signs of age-associated pathologies (e.g., muscle loss) as well as the accumulation of lipofuscin pigments, but no signs of tumorigenesis.

Indeed, for at least 80 % of their lives NMRs maintain normal activity, body composition, and reproductive and physiological functions with no obvious age-related increases in morbidity or mortality rate. Their long lifespan is attributed to sustained good health and pronounced cancer resistance. Clearly physiological and biochemical processes in this species have evolved to dramatically extend both their good health- and lifespan.

Scientists have tested various current theories using this species as an exceptionally long-lived animal model of successful abrogated aging. Surprisingly, NMRs have high levels of oxidative stress and relatively short telomeres, yet they are extremely resilient when subjected to cellular stressors and appear capable of sustaining both their genomic and protein integrity under hostile conditions. The challenge is to understand how these animals are able to do this. Elucidating these mechanisms will provide useful information for enhancing human life- and healthspan, making the naked mole rat a true "supermodel" for aging research and resistance to chronic age-associated diseases.

One of the mechanisms of age resistance could be revealed by Buffenstein R. et al. [2] where they show that neuregulin-1 is increased in these animals and can be one of the factors leading to resistance to age related disorders. Neuregulin-1 (NRG-1) signaling is critical for normal brain function during both development and adulthood. They have hypothesized that long-lived species will maintain higher levels of NRG-1 and that this contributes to their sustained brain function and concomitant maintenance of normal activity. They monitored the levels of NRG-1 and its receptor ErbB4 in H. glaber at different ages ranging from 1 day to 26 years and found that levels for NRG-1 and ErbB4 were sustained throughout development and adulthood. In addition, they compared seven rodent species with widely divergent (4-32y) maximum lifespan potential (MLSP) and found that at a physiologically-equivalent age, the longer-lived rodents had higher levels of NRG-1 and ErbB4. Moreover, phylogenetic independent contrast analyses revealed that this significant strong correlation between MLSP and NRG-1 levels was independent of phylogeny.

These results suggest that NRG-1 is an important factor contributing to divergent species MLSP through its role in maintaining neuronal integrity.

[1] Edrey YH, Hanes M, Pinto M, Mele J, Buffenstein R. ILAR J. Successful aging and sustained good health in the naked mole rat: a long-lived mammalian model for biogerontology and biomedical research.; 2011 Feb 8;52(1):41-53.

[2] Edrey YH, Casper D, Huchon D, Mele J, Gelfond JA, Kristan DM, Nevo E, Buffenstein R. Sustained high levels of neuregulin-1 in the longest-lived rodents; a key determinant of rodent longevity.; Aging Cell. 2011 Nov 21. doi: 10.1111/j.1474-9726.2011.00772.x. [Epub ahead of print]
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