OK, I hit the Naked mole-rats (NMRs). They're not pretty!
I would just like to point people towards Table 2, especially the lines Fasting glucose, GTT and insulin.
NMRs don't do insulin or, if they do, it is very different from ordinary rodent insulin. To the point where a normal rodent insulin assay simply can't find any insulin-like peptide in their blood.
Then there is Table 3 giving an HbA1c of 5.5%. Not suggestive of hypo or hyper glycaemia, with the normal caveats about HbA1c. BTW look at the HbA1c of normal lab mice. You too could be diabetic, just eat cr@pinabag.
NMRs also tend to fail GTTs:
"Surprisingly, NMRs even at a young age show impaired glucose tolerance (53), and insulin cannot be detected using rodent assays (Kang, Biney, and Buffenstein, unpublished data, 2004). We are currently assessing if this is because NMRs are naturally deficient in insulin or if their structure of insulin diverges to such an extent that it cannot be measured using common commercially available assays. Despite the apparent lack of insulin and abnormal glucose handling, glycated hemoglobin levels are low and similar in both 2- and 20-year-olds (Kang, Biney, and Buffenstein, unpublished data, 2004)."
Buffenstein has a bit to say on PUFA, DHA and D3 which are thought provoking.
I think it might be time to dig in to the pathological aspects of insulin sensitivity. We think of insulin sensitivity as a Good Thing. Well, maybe...
Peter
Humans already live around 5x as long as most mammals our size. This suggests to me that there is very little scope for significant life extension in humans.
ReplyDeleteLife expectancy is very similar in all first world countries so it is likely that diet and lifestyle actually make bugger-all difference to all causes mortality.
Okinawans actually have a marginally shorter lifespan than Americans when adjusted for road trauma and homicide.
Yes, Buffenstein makes the point that we are already way out on limb as a species. Interestingly we seem to be very different to NMRs
ReplyDeletePeter
What do you make of the fact that the NMR has a Vitamin D-independent calcium metabolism? Given how much hoopla surrounds the magical powers of Vitamin D it is interesting that longevity here correlates to a complete LACK of Vitamin D.
ReplyDeleteThe suppression of sex hormones for most of the lifetime in most of the species is also intriguing.
I would not read too much into the A1c as it is a very flawed measure even in humans. Given the many significant anomalies in the NMR it is very likely their red blood cells aren't typical either.
I would also want to know more about their insulin before drawing conclusions, too.
One question that comes to mind is what is the relation of hair to longevity. Humans are among the baldest mammals, but these little critters take it a step further.
The hair lack had crossed my mind too! A bit like the attractive physique (I speak for myself only here)!!!! There is a lot of very weird stuff about these beasts. I also thought the plot of lipid membrane composition against species body mass, which usually correlates positively with longevity, was interesting in that membrane DHA was negatively associated with species body size. What can you make of that? Not NMR related but... There's a fair bit to think about.
ReplyDeletePeter
BTW I've been chasing PUFA oxidation products in RBC cell membranes as markers of senesence, hence reducers of RBC life span. Not much joy. EPIC Norfolk has a negative correlation between PUFA intake and HbA1c, which is not what I'd expect in view of the positive association in the same study between HbA1c and both cardiac and all cause mortality. All just observational but...
Jenny NMRs have a diet comprised nearly entirely of cellulose. Presumably they obtain almost all their energy from volatile fatty acids produced via hind-gut fermentation. This means they are unlikely to have much variation in blood glucose and no need for insulin.
ReplyDeleteJenny humans were originally naked hairless tropical dwellers who synthesised massive mounts of vitamin D (8000iu/day) from sunlight. This meant our vitamin D metabolism has never evolved to be efficient.
ReplyDeleteFruit bats also have very low serum vitamin D being nocturnal frugivores with no dietary source of vitamin D.
NMRs live in a hot humid environment so body hair would be a huge liability.
Blogblog, an extreme form of the rabbit which lives largely but not totally on VFAs. In the non referenced LC books there are comments that pancreatectomy is of no issue to herbivores. Tracking this down has eluded me, though I have tried. Certainly chickens live on chicken food without a pancreas for months, though their glucose tolerance is poor. Mind you, this was Grundy's early work so he probably just made up the results. Oops, was that libel?
ReplyDeletePeter
Jenny, perhaps the naked mole rat evolved without a need for Vitamin D since it lives underground and would have no way to synthesize it without exposure to sunlight.
ReplyDeleteBlogblog,
ReplyDeleteThe ingestion of high dose vitamin D supplements can raise levels far beyond what is possible with sunbathing. It seems to me - and this is a very telling point I think - that if whites have retained the limitations on sun induced vitamin D levels for the 30,000 years they have been wearing clothes in N. Europe and going though 'D'-less winters there is good reason. Concomitantly there is good reason for not overwhelming the naturaly selected homeostatis of vitamin D by ingesting evolutionarily unprecedented amounts of 'D'. It's simply not credible that the limits on vitamin D (there are several including receptor polymophisms) have been inaccessable to natural selection.
That the NMR has a Vitamin D-independent calcium metabolism may be very significant
Hypervitaminosis D and premature aging: lessons learned from Fgf23 and Klotho mutant mice
"Such in vivo experimental studies indicated that excessive vitamin-D activity and altered mineral-ion homeostasis could accelerate the aging process" There are quite a few 'related articles' along similar lines.
For those giving their kids vitamin D
Infant Vitamin D Supplementation and
Allergic Conditions in Adulthood
Northern Finland Birth Cohort 1966
For a detailed discussion Mad dogs and ....
and the 4 following posts especially
Why are Europeans white?
I'll give it a rest about Vitamin D now.
Ken northern Europeans in the past would have obtained vastly higher sun exposure than modern people. This is because they would have spent most of their time outside. If they were engaged in physical activity such as hunting they could remain warm at very low temperatures and wear very little clothing.
ReplyDeleteSkiers often get sunburnt which shows that there is often adequate UV even in winter if you spend all day outside.
I tend to think is that insulin really only evolved as mechanism to allow mammals to handle glucose (from milk) during infancy. Once a mammal is weaned glucose (from glycogen) should be a very minor emergency energy source and the pancreas should have very work little to do. Adult mammals should be relying mostly on FFAs and VFAs for most of their energy.
ReplyDelete