10 replies to this topic

[Roses]

It is a little long post. But bear with me.

First the question of the long living creatures. Why do they live long?

There are few such creatures that are analyzed by the scientists. One is Storm petrel and another is the naked mole rat

Some scientists are of the view the peroxidation in the membranes of the cells is the main culprit in the aging.

http://rsbl.royalsoc...nt/4/4/351.full
Fowl play and the price of petrel: long-living Procellariiformes have peroxidation-resistant membrane composition compared with short-living Galliformes
William A Buttemer*, Harry Battam and A.J Hulbert
+ Author Affiliations

Almost full documentation is there.

Naked mole rat is the creature that is totally without a vitamin D in the body. Yet it
The Naked Mole-Rat: A New Long-Living Model for Human Aging Research
http://biomedgeronto...1/1369.abstract

Subterranean mole-rats naturally have an impoverished calciol status, yet synthesize calciol metabolites and calbindins
http://www.eje-onlin...tract/130/4/402

But it can process the vitamin D as any other mammal
http://joe.endocrino...stract/138/1/59

But how does this creature survive without the vitamin D in the body? Any other creature without the vitamin D would have rickets and other vitamin Def syndromes. Yet, instead of dying young, these creatures live long!

So I just checked if long living Leach's Storm-Petrel is also nocturnal.
Yes it is.

Next I checked the famed bats who are nocturnal mammals long living? Yes they are. Small sized bats of the size of small rodents live for more than 30 years. Whereas the same sized rodents would die in a year or two!

But does vitamin D is cause of the aging? So I checked if the hypervitaminosis of the Vitamin D produces aging phenotypes. Yes they are.
http://www.ncbi.nlm....pubmed/18177265
Klotho as a regulator of oxidative stress and senescence.
Klotho is a very important factor in the Vitamin D metabolism.

http://www.ncbi.nlm....pubmed/16731043
Trends Mol Med. 2006 Jul;12(7):298-305. Epub 2006 May 30.
Hypervitaminosis D and premature aging: lessons learned from Fgf23 and Klotho mutant mice.

The essential role of low levels of vitamin D during aging is well documented. However, possible effects of high levels of vitamin D on the aging process are not yet clear. Recent in vivo genetic-manipulation studies have shown increased serum level of vitamin D and altered mineral-ion homeostasis in mice that lack either fibroblast growth factor 23 (Fgf23) or klotho (Kl) genes. These mice develop identical phenotypes consistent with premature aging. Elimination or reduction of vitamin-D activity from Fgf23 and Kl mutant mice, either by dietary restriction or genetic manipulation could rescue premature aging-like features and ectopic calcifications, resulting in prolonged survival of both mutants. Such in vivo experimental studies indicated that excessive vitamin-D activity and altered mineral-ion homeostasis could accelerate the aging process.


But vitamin D is membrane antioxidant

http://www.ncbi.nlm..../pubmed/8325381

Vitamin D is a membrane antioxidant. Ability to inhibit iron-dependent lipid peroxidation in liposomes compared to cholesterol, ergosterol and tamoxifen and relevance to anticancer action.
Wiseman H.

But Vitamin D is very much processed by Klotho. But the Klotho production falls as we age. So as we age, more vitamin D remains as not processed which can lead to aging.

Second, the vitamin D is not a very good membrane antioxidant. This may produce byproducts which lead to aging. Against Vitamin D, these nocturnal mammals and birds have evolved a different membrane antioxidant and mineral fixing chemical which leads to slower aging or even reversal of aging as we see in the storm petrel growing the telomeres as they age.

So, I think Vitamin D is the culprit. Let me clarify and reiterate. First is the case of the Naked Mole rats who do not depend on the vitamin d to fix the calcium. The grow the teeth so fast and they have to constantly dig to reduce the size of their teeth. But they have no vitamin d in their body and they live 9 times more than similarly sized rodents. It is hypothesized that there might be someother vitamin d analogue that is produced by its own body with out the need of the sun to create the vitamin d.

Second is the case of vitamin d overdose that is produced by the klotho gene absence and the symptoms are very similar to progeria.

But there are many nocturnal animals and birds that do not come in the sun and have the same or better and longer life span of the animals of the same size. These nocturnal animals/birds have no rickets or vitamin d deficiency. If so, they would not have evolved at all.

So here is my hypothesis. Vitamin D is a necessary part of the evil of aging. without the Vitamin D, humans cannot survive. But the very fact of the vitamin d in the metabolism produces the factors that should be implicated in the aging.

There are animals that have developed the nocturnal behaviour fall in two categories. One that eat other animals to get their vitamin d. another set that are Naked mole rat and storm petrels that are having a vitamin d independent metabolism with a specific analog (let us say that is yet to be discovered)

So the sunlight is the culprit. That is what is making us age. But the answer is the find the analog that is helping the storm petrels and nmrats to survive without the vitamin D.

So it may be true that the vampires are afraid of sunlight! Now we know why !

[e Volution]

Interesting theory, I have a feeling it will get majorly shot down by the resident experts however...

I'll admit I still haven't read ending aging yet, but I think it is pretty well accepted (certainly around here) that aging is a very complex and multifaceted affair with numerous independent factors constantly taking place mostly as a byproduct of metabolism. Viewed this way a simple hypothesis such as yours is essentially impossible to be correct.

Humans are long-lived animals. We outlive these animals you have cited as avoiding aging through not utilising Vitamin D. But they still age and die don't they, so how does your hypothesis explain that?

[VidX]

It'd be more interesting to know what kind of mechanism exists in these animals, that substitutes for a vit.D function (I mean - if we'd live under the rock all the time or deep in the sea - chances are - we wouldn't have evolved a way to synthesize vit.D in our skin too...

Edited by VidX, 07 October 2010 - 12:40 AM.

[Roses]

Interesting theory, I have a feeling it will get majorly shot down by the resident experts however...

I'll admit I still haven't read ending aging yet, but I think it is pretty well accepted (certainly around here) that aging is a very complex and multifaceted affair with numerous independent factors constantly taking place mostly as a byproduct of metabolism. Viewed this way a simple hypothesis such as yours is essentially impossible to be correct.

Humans are long-lived animals. We outlive these animals you have cited as avoiding aging through not utilising Vitamin D. But they still age and die don't they, so how does your hypothesis explain that?

I think, aging cannot be avoided . Even these long living creatures do die. Only that they have a long life compared to one expected based on their body mass. These animals do have the mechanism of vitamin d process. Only that they do not use it because they have no vitamin d. I am not saying they would not die at all. My goal is to see if vitamin d is the major factor in aging. If that is the main culprit, then replace that with the analog should give 3 or four times the current life span. That should be good enough as of now.

So here is the testable hypothesis.
1) we identify the mechanism by which these alteranate mineral fixing works. It is usually by a vitamin d analogue.
2) give this analog to the rodents in the labs and test how long they live and shield them from the sunlight


Check if they live long .. if they do, how long

[DaffyDuck]

This is an interesting topic and it's funny because I was literally just reading about the naked mole rat and I come here and see this.

We know that Vitamin D helps reduce inflammatory cytokines so in that respect it should be anti-aging. I think it's main contribution is keeping the immune system healthy by reducing telomere loss (by some unknown method, perhaps reduced cell turnover via reduced inflammation) and that can increase lifespan by warding off cancer, infectious diseases, etc. My guess would be that it doesn't increase maximum lifespan. I've often thought of the immune system as a necessary evil with respect to aging but I'm not confident about it. Obviously the naked mole rat has to contend with similar viral and bacterial agents as we do. How do they do it and live so comparatively long?

It's an interesting animal to study since it's a mammal, unlike some of the other long lived animals like the rougheye rockfish. Also, they rarely get cancer. We need to know why that is.

http://www.ncbi.nlm..../pubmed/8384476

Naked mole rats (Heterocephalus glaber) lead a strictly subterranean existence and appear to be naturally deficient in cholecalciferol (D3). Oral supplementation with D3 (Ds) led to a 1.8-fold increase in food intake and the associated enlargement (1.4-fold) of the caecum. The effect of Ds, and the concomitant increase in food intake, on caecal fermentation efficiency when animals were fed on a carrot-based diet was determined by measuring the rate of both gas production and short-chain fatty acid (SCFA) production. Microbial-controlled fermentation processes in the caecum were enhanced with Ds when compared with animals not receiving a D3 supplement (Dn). Both the rates of gas production (Dn 10.76 (SE 0.77), Ds 15.20 (SE 1.77) ml/g dry matter (DM) per h) and SCFA production (Dn 463.0 (SE 33.7), Ds 684.3 (SE 74.8) mumol/g DM per h) increased more than 1.4-fold per g DM caecal substrate. These factors contributed to the higher digestibility of the food in Ds animals. The larger quantity of energy available to D3-replete naked mole rats was not used in anabolic processes, for these animals maintained mass. These findings suggest that metabolic rate in D3-replete animals was elevated. Thus, despite improved gut function, D3-replete animals may be disadvantaged by their higher energy and food requirements in their natural milieu.

EDIT: Removed cancer studies to keep on topic. Also, there is more discussion here:
http://www.imminst.o...celerate-aging/

Edited by DaffyDuck, 07 October 2010 - 01:33 PM.

[DaffyDuck]

http://www.ncbi.nlm....pubmed/19500727

Hypervitaminosis vitamin D(3) has been recently implicated in premature aging through the regulation of 1alpha hydroxylase expression by klotho and fibroblast growth factor-23 (Fgf-23). Here we examined whether the lack of hormonal function of vitamin D(3) in mice is linked to aging phenomena. For this, we used vitamin D(3) receptor (VDR) "Tokyo" knockout (KO) mice (fed with a special rescue diet) and analyzed their growth, skin and cerebellar morphology, as well as overall motor performance. We also studied the expression of aging-related genes, such as Fgf-23, nuclear factor kappaB (NF-kappaB), p53, insulin like growth factor 1 (IGF1) and IGF1 receptor (IGF1R), in liver, as well as klotho in liver, kidney and prostate tissues. Overall, VDR KO mice showed several aging related phenotypes, including poorer survival, early alopecia, thickened skin, enlarged sebaceous glands and development of epidermal cysts. There was no difference either in the structure of cerebellum or in the number of Purkinje cells. Unlike the wildtype controls, VDR KO mice lose their ability to swim after 6 months of age. Expression of all the genes was lower in old VDR KO mice, but only NF-kappaB, Fgf-23, p53 and IGF1R were significantly lower. Since the phenotype of aged VDR knockout mice is similar to mouse models with hypervitaminosis D(3), our study suggests that VDR genetic ablation promotes premature aging in mice, and that vitamin D(3) homeostasis regulates physiological aging.

http://www.ncbi.nlm....pubmed/19444937

Recent studies using genetically modified mice, such as FGF23-/- and Klotho-/- mice that exhibit altered mineral homeostasis due to a high vitamin D activity showed features of premature aging that include retarded growth, osteoporosis, atherosclerosis, ectopic calcification, immunological deficiency, skin and general organ atrophy, hypogonadism and short lifespan. The phenotype reversed by normalizing vitamin D and/or mineral homeostasis. Thus, hypervitaminosis D due to an increased 1alpha-hydroxylase activity seems to be a cause of the premature aging. In several studies, we have described that a complete or partial lack of vitamin D action (VDR-/- mice and CYP27B1-/-) show almost similar phenotype as FGF23-/- or Klotho-/- mice. VDR mutant mice have growth retardation, osteoporosis, kyphosis, skin thickening and wrinkling, alopecia, ectopic calcification, progressive loss of hearing and balance as well as short lifespan. CYP27B1-/- mice do not show alopecia nor balance deficit, which might be apoVDR-dependent or calcidiol-dependent. The features are typical to premature aging. The phenotype is resistant to a normalization of the mineral homeostasis by a rescue diet containing high calcium and phosphate. Taken together, aging shows a U-shaped dependency on hormonal forms of vitamin D suggesting that there is an optimal concentration of vitamin D in delaying aging phenomena. Our recent study shows that calcidiol is an active hormone. Since serum calcidiol but not calcitriol is fluctuating in physiological situations, calcidiol might determine the biological output of vitamin D action. Due to its high serum concentration and better uptake of calcidiol-DBP by the target cells through the cubilin-megalin system, calcidiol seems to be an important circulating hormone. Therefore, serum calcidiol might be associated with an increased risk of aging-related chronic diseases more directly than calcitriol. Aging and cancer seem to be tightly associated phenomena. Accumulation of damage on DNA and telomeres cause both aging and cancer, moreover the signalling pathways seem to converge on tumour suppressor protein, p53, which seems to be regulated by vitamin D. Also, the insulin-like growth factor signalling pathway (IGF-1, IGFBPs, IGFR) and fibroblast growth factor-23 (FGF-23) regulate growth, aging and cancer. Vitamin D can regulate these signalling pathways, too. Also NF-kappaB and telomerase reverse transcriptase (TERT) might be molecular mechanisms mediating vitamin D action in aging and cancer. Calcidiol serum concentrations show a U-shaped risk of prostate cancer suggesting an optimal serum concentration of 40-60 nmol/L for the lowest cancer risk. Therefore, it is necessary to study several common aging-associated diseases such as osteoporosis, hypertension and diabetes known to be vitamin D-dependent before any recommendations of an optimal serum concentration of calcidiol are given.

[VidX]

I think, aging cannot be avoided . Even these long living creatures do die.

There's really no valuable data regarding this, as for ex. one of the whales who live veeery long die without any detectable aging patterns, but because their loose their sight and bump into ship or something. The eyesight lost reason is not related to aging (more like it get's "clogged" or something similart..)..

[james41]

in my opinion with all due respects I think you are missing the big picture here, what this animals have in comun is that living at night when most predators are sleeping, this trough the evolution of a specie give them chances to geneticaly invest in longevity genes instead of reproduce fast and a lot and age soon.

that is the real comun thing that long live species have, they have very little predators,mole rats live under the earth where almost no predator gets them, bats fly, are very skilled at flying and live at night that reduce predators tremendously, humans have inteligence to avoid predators, elephants are way to big to be killed eassily by predators, wheals is one of the biggers and more predator free specie in mammals ( not a coincidence some can live to 150 years),

from an evolutionary perspective what is the point to invest in longevity for a specie if is gonna be eaten for sure in their youth??better invest in early reproduction and extensive fertility, so your specie doesnt extiguish.

same animals from australian continent live much more than the european same specie and the proposal reason for this is that when both continents separated australia was a relatively predators free enviroment so that made the longevity genes investment posible.


I think vit D is really not the conection here, but of course I may be wroung

[Roses]

that is the real comun thing that long live species have, they have very little predators,mole rats live under the earth where almost no predator gets them, bats fly, are very skilled at flying and live at night that reduce predators tremendously, humans have inteligence to avoid predators, elephants are way to big to be killed eassily by predators, wheals is one of the biggers and more predator free specie in mammals ( not a coincidence some can live to 150 years),

the existance of the Predators is not the issue.
The size of the animal is the issue.
The size determines the longevity of the animal. Say for example a small rodent.. lives for 1 year. Whereas the elephant lives for long almost 80 years. Small birds die off in few years. Whereas the big birds live for long.
So this correlation between the size and the longevity is a recorded one.
http://en.wikipedia...._metabolic_rate


The exceptions to the above rules are the naked mole rats and Leach's storm petrels and other nocturnal animals.

So these specific long living animals are investigated for their longevity (compared to the size)

[james41]

that is the real comun thing that long live species have, they have very little predators,mole rats live under the earth where almost no predator gets them, bats fly, are very skilled at flying and live at night that reduce predators tremendously, humans have inteligence to avoid predators, elephants are way to big to be killed eassily by predators, wheals is one of the biggers and more predator free specie in mammals ( not a coincidence some can live to 150 years),

the existance of the Predators is not the issue.
The size of the animal is the issue.
The size determines the longevity of the animal. Say for example a small rodent.. lives for 1 year. Whereas the elephant lives for long almost 80 years. Small birds die off in few years. Whereas the big birds live for long.
So this correlation between the size and the longevity is a recorded one.
http://en.wikipedia...._metabolic_rate


The exceptions to the above rules are the naked mole rats and Leach's storm petrels and other nocturnal animals.

So these specific long living animals are investigated for their longevity (compared to the size)

there are way two many exceptions to this rule to be consider a fact.

the main one is birds, most flying birds live much longer and with less aging signs than most not flying mammals with same metabolic rates and sizes.Not only a little bit longer but substantially longer.

Also flying mammals like bats live subtantianly longer than non flying mammals with even lower metabolic rates than same size mammals.

In my opinion as a simple example one could have the theory that as blond , blue eyes, fair skin individuals have higher on average vit D levels(compared to people living in the same geografic area) one could mistakenly see this as, the higher the vitamine D levels the less melanin you produce(or less tirokinase activity).

While it is the other way arround it is the lighter the skin is the more vit D can be produce in the body trough sun radiation.

In this case of course if the real culprit is tha the less predators the longer life span, one could mistankenly understand that as bigger animals on average have less predators(as they are stronger on average) then one could thing it is the size what is related to the life span, but this theory has way too many exceptions to be the real reason.Being bigger and having a longer life span, has the comun correlation, that both decrease predators.


But how do you explain the longer live of apes, and humans compared to that are much bigger, giraffe, rinos, and so on and so on.....

Mole rats, bats, compared cats, dogs that are much smaller.
and almost all birds compared to much bigger mammals.

why too many exceptions to be the real reason.


the less predators are the comun thing in them.

How do you avoid predators?.


Being inteligent.
being big and strong
being fast.
being nocturnal
living under the earth
flying
being a predator your self(predators live longer on average than hervivors animals the same size)
being a social animal gives you protection by being defended by your pack.
having exoskeleton shell

there is strong correlations in all this characteristics and long live species . But the real reason behind them as it was very well today at the belgium conference bythe fantastic Prof. Dr. Michael Rose , is that as they lack predators, they can reach a longer and longer age to reproduce therefor the longevity genes are favoured while the ones that kill you soon are dismished(as Prof Michael Rose explained today with the flyes experiment.

[Roses]

It'd be more interesting to know what kind of mechanism exists in these animals, that substitutes for a vit.D function

Yes
That is my interest too