Naked mole rats are well studied by the aging research community: there are large colonies of naked mole rats in US laboratories, and a steady output of new papers on naked mole rat biology from numerous research groups. Their genome was sequenced in 2011, in advance of many other species that you might consider more pressing candidates. Naked mole rats are interesting to scientists for a number of reasons, the most important of which are that (a) they live nine times longer than similarly sized rodent species and (b) are immune to cancer. Researchers hope that there is something to be learned here about the relative importance of different metabolic processes in degenerative aging, and further that the biological mechanisms by which naked mole rats suppress cancer so effectively might lead to a form of cancer therapy for humans.
I noticed a couple of recent papers on the topic of naked mole rat biology, starting with the usual consideration of oxidative damage in aging, which is one of the areas where this species is strikingly unusual. An old naked mole rat has all the measures of a very high load of oxidative damage, but none of the degeneration that another rodent species would be exhibiting with those same measures. Their biochemistry in some way shrugs off the consequences of such damage - you might look at the membrane pacemaker theory of longevity for some further context on this research.
The 'oxidative stress theory of aging' predicts that aging is primarily regulated by progressive accumulation of oxidized macromolecules that cause deleterious effects to cellular homeostasis and induces a decline in physiological function. However, our reports on the detection of higher level of oxidized protein carbonyls in the soluble cellular fractions of long-living rodent naked-mole rats (NMRs, lifespan ∼30yrs) compared to short-lived mice (lifespan ∼3.5yrs) apparently contradicts a key tenet of the oxidative theory.
As oxidation often inactivates enzyme function and induces higher-order soluble oligomers, we performed a comprehensive study to measure global protein carbonyl level in different tissues of age-matched NMRs and mice to determine if the traditional concept of oxidation mediated impairment of function and induction of higher-order structures of proteins are upheld in the NMRs. We made three intriguing observations with NMRs proteins: (1) protein carbonyl is significantly elevated across different tissues despite of its exceptional longevity, (2) enzyme function is restored despite of experiencing higher level of protein carbonylation, and (3) enzymes show lesser sensitivity to form higher-order non-reducible oligomers compared to short-living mouse proteins in response to oxidative stress.
These unexpected intriguing observations thus strongly suggest that oxidative modification may not be the only criteria for impairment of protein and enzyme function; cellular environment is likely be the critical determining factor in this process and may be the underlying mechanism for exceptional longevity of NMR.
In another paper we find that naked mole rats also appear to laugh in the face of their version of amyloid beta, the aggregate that shows up in damaging clumps in late stage Alzheimer's disease. Old naked mole rats naturally have as much amyloid beta as mice deliberately engineered to have high levels of amyloid beta, and apparently suffer few or no ill effects as a result.
Amyloid beta (Aβ) is implicated in Alzheimer's disease (AD) as an integral component of both neural toxicity and plaque formation. Brains of the longest-lived rodents, naked mole-rats (NMRs) approximately 32 years of age, had levels of Aβ similar to those of the 3xTg-AD mouse model of AD. Interestingly, there was no evidence of extracellular plaques, nor was there an age-related increase in Aβ levels in the individuals examined (2-20+ years).
The NMR Aβ peptide showed greater homology to the human sequence than to the mouse sequence, differing by only 1 amino acid from the former. This subtle difference led to interspecies differences in aggregation propensity but not neurotoxicity; NMR Aβ was less prone to aggregation than human Aβ. Nevertheless, both NMR and human Aβ were equally toxic to mouse hippocampal neurons, suggesting that Aβ neurotoxicity and aggregation properties were not coupled. Understanding how NMRs acquire and tolerate high levels of Aβ with no plaque formation could provide useful insights into AD, and may elucidate protective mechanisms that delay AD progression.