15 replies to this topic

[olaf.larsson]

Is this true?

"If you assume that somatic mutation theory is true a polyploid organism should age slower than the same organism in diploid state."

[John Schloendorn]

Other things being equal - yes. But other things are not equal.

As for actual organisms that can change their ploidity (such as yeast), they do this as part of a developmental program, and anything and everything can be changed by such a program.

Even if polyploidity were artificially induced, it would furthermore depend on the nature of the particular mutations. Your statement would be true for recessive mutations only. Dominant-negative mutations would in fact become more likely to cause a negative phenotype when you increase ploidity.

What polyploidity would do is allow for effective double stranded break repair by recombination from the redundant copies. Too bad that polyploidity in humans is usually associated with mental retardation.

[olaf.larsson]

One interessting thing I read today, is that salamander larvae that are monoploid have five times smaler cells than salamander larvae that are pentaploid. Yet the both salamanderlarvae look the same. Only in the microscope you can see that the pentaploid type must consist of 5 times less cells then the monoploid since the cells in the pentaploid are five times as large.

[John Schloendorn]

Reading Alberts, are you? Excellent book :-)

[John Schloendorn]

does it actually say anything about DNA repair in those creatures?

[susmariosep]

This must be the sixth time I opened this thread and wondered what I could add, and realized I don't know what is a polyploid organism and what is the diploid state of an organism, and even worse, what is the theory of somatic mutation.

Is this true?

"If you assume that somatic mutation theory is true a polyploid organism should age slower than the same organism in diploid state."

Dear good people here, I beg of you to explain to me in your patient mood and with exhausting your didactic skills, the following for me, so that I will add more knowledge to my mind; for as the stomach is built for food storage and processing, so also the mind is designed for accessing knowledge, and thereby acquainting man more widely and deeply with his own existence and the world wherein and whereby he lives, namely, the following concepts:

1. Somatic mutation theory,


2. Polyploid organism,

3. Diploid state of an organism.

Remember: someone two thousand years back exhorted everyman to teach every other man who is ignorant, one of the spiritual works of mercy: Teach the ignorant. He inculcated the idea that we are all brothers, that's why.

I will honor you as my teachers for this favor.

Susma

[John Schloendorn]

Susma, since I so thoroughly enjoy your every mention of this guy 2000 years back and the various implications he drew (Or, maybe I should say, every single one of your posts I can find), I will rush to share what I know about these terms. (Not that I wouldn't otherwise). Whatever. Here we go.

1. Somatic mutation theory ist the tenet that most symptoms of aging are gradually caused by random changes in the DNA of your body's cells, as caused by chemicals, radiation, or wear and tear.
(Body cells are also known as somatic cells, as opposed to germ cells, which can pass their DNA to the next generation. Somatic cell mutation theory is consistent with the observation that DNA repair in the germ cells is much better, so that babys come out young.)

2+3. Ploidity is the number of redundant copies of identical genetic information in a cell. For example, most human cells have only one copy of each gene and are said to be monoploid, while others have two identical copies and are diploid, ect.
Now a polyploid organism is one that usually has more than two identical copies of each gene.

Getting the idea behind Wolfram's post ? :-)

Cheers.

[Cyto]

Mmm, to throw something out...

I was reading DNA damage and aging from Mech. of Ageing and Development (May 2004) and it talked about the trade-off of having redundancies vs. more clean-cut genomes and the talk led to avian lifespans. I guess that avians who have a more active lifestyle live longer than the opposite which acts as an inverse for our normal model. They have a genome which carries out homologous recombination almost absolutely due to the lack of redundancy in genes, in opposite of ours which is non-homologous DNA end-joining (mainly). With NHEJ you can typically loose bases but with HR you typically don't so the higher production of oxi-rads causes less erosion in avian than say, us. They didn't have a direct answer to the phenomena but rather that the reducing glutathione may be upregulated massively and, of course, they have some model dsBreak repair prots. Bats are also looked at due to their avian-like genome setup.

Some neat data from this article:

1% of oxygen we breathe is converted into oxi-radicals which amounts to <3x10^22 free radicals per person every hour.

Two-hundred million gamma rays pass through an average size human every hour from the decay of naturally-occurring radionuclides in the earth.

Its estimated that under strong sunlight typically at a beach an exposed epidermal cell will occur about 40,000 damage sites in one hour, primarily due to UV absorption.


Interesting stuff.

[John Schloendorn]

Bates, I would suppose that Birds, like us, have most cells in G0 and therefore cannot do homologous recombination repair in those cells. Does the paper say anything about that?

[John Schloendorn]

I vaguely remember some SENS1 speaker found that birds' complex1 is less electron-leaky and attributed bird life expectancy to this.

[olaf.larsson]

Hmmm... I can only imagine how confusing some of the posts here could be for non-lifescientist. Wouldn´t it be good idea to try various respiratory complex inhibitors and see if they could extend lifespan? There are many of them, NaCN is one. A mix of respiratory complex inhibitors could inhibit respiration and decrease free radical formation without killing the organsim. But i guess someone has tried this allready.

[Cyto]

Yep, they talked about avians having higher energy expendature per gram of tissue yet will live 4-10 times longer than mammalian counterparts. They then say that its due to lower ROS production even given the ammount of oxygen consumed. Thought to be the more efficient mitochondrial respiratory chain and maybe antioxidants (but this is less than a two-fold upreg).

As for the G0 phase, heh, they used studies in avian B cell lines and embryonic fibroblasts. But I could see this still being a practical application in adult basal epidermal divisions. And don't most avians have the ability to replace massive neural loss? Basic cell replacement, where applicable, could act as the error check (G0 induced to reenter G1).

[susmariosep]

Thanks, Schloendorn, for your goodness.

Just some more questions, and I will be off.


1. Somatic mutation theory ist the tenet that most symptoms of aging are gradually caused by random changes in the DNA of your body's cells, as caused by chemicals, radiation, or wear and tear.
(Body cells are also known as somatic cells, as opposed to germ cells, which can pass their DNA to the next generation. Somatic cell mutation theory is consistent with the observation that DNA repair in the germ cells is much better, so that babys come out young.)

Tell me if I am wrong: Both in somatic cells and in germ cells the DNA deteriorates with aging in an organism; but restorative repair can be effected, and logically better done in the DNA of germ cells. In this connection, better have children while still young.


2+3. Ploidity is the number of redundant copies of identical genetic information in a cell. For example, most human cells have only one copy of each gene and are said to be monoploid, while others have two identical copies and are diploid, ect. Now a polyploid organism is one that usually has more than two identical copies of each gene.

Again tell me if I am wrong: The more copies a cell has of its genetic information the longer it can survive, owing to possible restorative "repair by recombination from the redundant copies". Sounds something like the why of maintaining two copies of FAT in computer disk storages?

Don't bother to reply to this post if you need to write at length to explain your answers.

Thanks again, for being a patient teacher to me.

Susma

[John Schloendorn]

Wolfram: Depriving cells of Oxygen is an established way to extend their viability in culture. This is attributed to decreased oxidative stress from respiration. The use of specific inhibitors is discussed in the SENS1 talk by Gustavo Barja. Btw, I'd rather warn against eating cyanide in vivo. Already the Romans practiced that a lot, every time one of them was unhappy with the emperor.

Bates: Good stuff, I got the paper, I'll do my homework as I get the chance.

Susma:
Nay worries, keep asking what's on your mind, that's what we're here for!

1. Yes, thats right. Having children early is especially important for women, because eggs, unlike sperm, are made early in life and then maintained in the monoploid state where they cannot be repaired from the 'backup FAT'. Though once a baby is being made, you get an additional selection process to make sure only cells that are in genetically good shape make it.

2. Yep, you got it.

Thanks for being a good student :-)

[olaf.larsson]

Untill recently I was quite sure that somatic mutation theorie was the closest you can come to the true but...

If the somatic mutation theorie of aging would be true, one could expect that all individuals with impaired DNA repair would have accelerated aging phenotype, that clearly is not the case. All DNA repair impaired individuals have higher cancer rates though. So is aging some special kind of mutations or is it something else???

[John Schloendorn]

Hmm I would say that all individuals with impaired DNA repair show a phenotype that could constitute a good part of, or contribution to the aging phenotype. Thus I would say it is one contributing cause, but we cannot precisely weigh the different causes at this time.