44 replies to this topic

[ihatesnow]

More attention being given to epigenetics

Genes, which carry the specific instructions necessary to make proteins do the work of the cell, vary by only about 0.025 percent across all humans. Scientists have spent decades trying to understand how these tiny differences affect who we are and what we become. In contrast, non-coding regions of the genome, which account for approximately 98 percent of our DNA, vary in their sequence by about 1 to 4 percent. But until recently, scientists had little, if any, idea what these regions do and how they contribute to the "special sauce" that makes me, me, and you, you.

Now Snyder and his colleagues have found that the unique, specific changes among individuals in the sequence of DNA affect the ability of "control proteins" called transcription factors to bind to the regions that control gene expression. As a result, the subsequent expression of nearby genes can vary significantly.

"People have done a lot of work over the years to characterize differences in gene expression among individuals," said Snyder. "We're the first to look at differences in transcription-factor binding from person to person." What's more, by selectively breeding, or crossing, yeast strains, Snyder and his colleagues found that many, but not all, of these differences in binding and expression levels are heritable.

http://news.yahoo.co.../us_cancer_rnai

[ihatesnow]

More attention being given to epigenetics

Genes, which carry the specific instructions necessary to make proteins do the work of the cell, vary by only about 0.025 percent across all humans. Scientists have spent decades trying to understand how these tiny differences affect who we are and what we become. In contrast, non-coding regions of the genome, which account for approximately 98 percent of our DNA, vary in their sequence by about 1 to 4 percent. But until recently, scientists had little, if any, idea what these regions do and how they contribute to the "special sauce" that makes me, me, and you, you.

Now Snyder and his colleagues have found that the unique, specific changes among individuals in the sequence of DNA affect the ability of "control proteins" called transcription factors to bind to the regions that control gene expression. As a result, the subsequent expression of nearby genes can vary significantly.

"People have done a lot of work over the years to characterize differences in gene expression among individuals," said Snyder. "We're the first to look at differences in transcription-factor binding from person to person." What's more, by selectively breeding, or crossing, yeast strains, Snyder and his colleagues found that many, but not all, of these differences in binding and expression levels are heritable.

http://news.yahoo.co.../us_cancer_rnai

http://www.scienceda...00318141536.htm

[Mind]

Just another recent interesting finding on epigenetic inheritence. I thought it fit well in this thread.

Although much more research remains to be done, the new study raises the tantalizing possibility that if Grandma practiced caloric restriction—which affects the expression of longevity-enhancing genes—her descendants might reap the benefits.
The inheritance occurs through "epigenetics": alterations not in the coding sequence of DNA (those ubiquitous A's, T's, C's, and G's) but in chemical changes that affect whether genes are expressed. One such change involves histones, proteins that act as spools for a cell's long strands of DNA. Some of the best-known longevity genes, those belonging to the Sir2 family, make proteins that alter histones.

[Mind]

A study comparing methylation newborns vs. the elderly. Now we are getting some decent data: http://www.pnas.org/...2.full.pdf html

[niner]

A study comparing methylation newborns vs. the elderly. Now we are getting some decent data: http://www.pnas.org/...2.full.pdf html

In their introduction, they say:

During human aging, progressive impairment of organ and tissue functionality leads to an increasing probability of death. The molecular culprits behind this decline in physiological activities remain largely unknown.

This is rather entirely at odds with what the people at SENS would tell us. The SENS position is that nuclear mutations and epimutations don't matter, except for the extent to which they lead to cancer. Jim Watson has a new three-part post on Vince Giuliano's blog regarding the similarities between cancer and aging, with a large epigenetic component. I think Aubrey's position (if I recall correctly) boils down to nuclear (epi-) mutations being too infrequent and too random to have a major effect on phenotype. I suppose that if epimutations were widespread and coordinated, then maybe they could play a role in aging.

[Musli]

http://sens.org/outr...cell-methylomes
In three month's time, this will definitely shed some light on the topic. Hoping for a high-quality video of the talk.

[HighDesertWizard]

This is rather entirely at odds with what the people at SENS would tell us. The SENS position is that nuclear mutations and epimutations don't matter, except for the extent to which they lead to cancer. Jim Watson has a new three-part post on Vince Giuliano's blog regarding the similarities between cancer and aging, with a large epigenetic component. I think Aubrey's position (if I recall correctly) boils down to nuclear (epi-) mutations being too infrequent and too random to have a major effect on phenotype. I suppose that if epimutations were widespread and coordinated, then maybe they could play a role in aging.

 

 

Wow. If that's the SENS position, they certainly got themselves into an untenable position...

Here's an essay by a guy whose blog I like, Josh Mitteldorg.
 

How does the body know how old it is? Introducing the epigenetic clock hypothesis

 

Here's a link to his most recent blog entry entitled Open Letter on Research Priorities in Aging. A very interesting discussion of a few kinds of aging clocks...

[niner]

 

This is rather entirely at odds with what the people at SENS would tell us. The SENS position is that nuclear mutations and epimutations don't matter, except for the extent to which they lead to cancer. Jim Watson has a new three-part post on Vince Giuliano's blog regarding the similarities between cancer and aging, with a large epigenetic component. I think Aubrey's position (if I recall correctly) boils down to nuclear (epi-) mutations being too infrequent and too random to have a major effect on phenotype. I suppose that if epimutations were widespread and coordinated, then maybe they could play a role in aging.

 

Wow. If that's the SENS position, they certainly got themselves into an untenable position...

Here's an essay by a guy whose blog I like, Josh Mitteldorg.
 

How does the body know how old it is? Introducing the epigenetic clock hypothesis

 

Here's a link to his most recent blog entry entitled Open Letter on Research Priorities in Aging. A very interesting discussion of a few kinds of aging clocks...

 

Why is that position untenable?  Josh is infatuated/obsessed with a programmed aging hypothesis, and he has attracted some like-minded true believers to his blog.  As smart as he is, and as good a writer as he is, Josh gets some things wrong.   I'm afraid that he's just taken a wrong turn with the whole programmed aging thing.

[Avatar of Horus]

...
Children with the fatal genetic disease Hutchinson-Gilford progeria syndrome (HGPS) seem to grow old before their time. They lose their hair, their skin thins, their bones grow brittle, and their arteries clog (see "Of Hyperaging and Methuselah Genes"). ...

the provided link's abstract version says: "This article originally appeared in SCIENTIFIC AMERICAN Presents ... The Quest to Beat Aging (Summer 2000). "
The full version is available on the Scientific American website: http://www.scientifi...thuselah-genes/

[HighDesertWizard]

 

 

This is rather entirely at odds with what the people at SENS would tell us. The SENS position is that nuclear mutations and epimutations don't matter, except for the extent to which they lead to cancer. Jim Watson has a new three-part post on Vince Giuliano's blog regarding the similarities between cancer and aging, with a large epigenetic component. I think Aubrey's position (if I recall correctly) boils down to nuclear (epi-) mutations being too infrequent and too random to have a major effect on phenotype. I suppose that if epimutations were widespread and coordinated, then maybe they could play a role in aging.

 

Wow. If that's the SENS position, they certainly got themselves into an untenable position...

<< snip >>

 

Why is that position untenable? << snip >>

 

niner... One question at a time. I'll respond to the point about Mitteldorf in a bit... But first...

 

I'm not familiar with the details of the SENS position on Epigenetics. There is this...

 

-->> "The rapid evolution of longevity in mammals suggests the involvement of relatively few genes, as also the inherent immortality of embryonic stem cells in vitro, suggests that replicative senescence - as possibly organismal aging - are epigenetic phenomena"

 

Are you suggesting that Epigenetic phenomenon vis-a-vis morbidity and mortality really don't matter? I'm having a hard time believing that you believe that's a credible position to hold.

By this date, there must be from 100 to 1000 studies that demonstrate the importance of Epigenetic phenomenon to morbidity and mortality.

What have I misunderstood, what am I missing? How can believing those studies "don't matter" be a credible position to maintain?

Edited by wccaguy, 01 November 2014 - 05:09 PM.

[HighDesertWizard]

Just noticed that the link I provided to a SENS paper, was from a SENS 6 Conference paper. SENS 6... September 2013...

 

If that's a State of the SENS Art paper vis-a-vis Epigenetics and Aging as of Sept13, then, I'm sorry to say that the SENS initiative is far behind the State of the Science other people are doing about this important dimension of the longevity puzzle.

 

What am I missing?

[HighDesertWizard]

A study comparing methylation newborns vs. the elderly. Now we are getting some decent data: http://www.pnas.org/...2.full.pdf html

 

Mind... IMO, the study you reference doesn't highlight the importance of Epigenetic phenomenon as a variable associated with aging as much as does study by Steve Horvath. A Nature summary story about key findings of the study is here. The study itself is at the link below.

 

DNA methylation age of human tissues and cell types

[mpe]

Personally, I think Josh might well be right. His arguments and supporting references seem compelling.

Yes I have read his blog and references.

 

 

Mike

[corb]

What am I missing?

 

From one of the papers on Mittledorf's blog:

 

 

Beyond the genome and the epigenome, cellular aging is characterized by the accumulation of damaged macromolecules, including proteins and lipids, and highly stable aggregates of those molecules (Campisi and Vijg, 2009)

 

Extracellular matrix stiffening, extracellular aggregates, intracellular aggregates are still very much on the table. So are senescent cells, because the "epigenetic "clock"" is not a measure of cell senescence or mitotic age (from another of the papers on Mittledorf's blog). Epigenetic reprogramming won't help with mitochondrial damage either. And so on.

 

Basicaly the only strand of SENS affected by these epigenetic theories is the regenerative strand. But that's also the strand SENS have the least interest in considering it's already quite well funded and researched by the mainstream - and the same people working on stem cells are working on epigenetic reprogramming as well so really, I don't think the SENS foundation will be severely interested to take part in the research either way.

 

The easiest way to know for sure is to contact someone from SENS and asking them directly about it.

[HighDesertWizard]

 

What am I missing?

 

From one of the papers on Mittledorf's blog:

 

 

Beyond the genome and the epigenome, cellular aging is characterized by the accumulation of damaged macromolecules, including proteins and lipids, and highly stable aggregates of those molecules (Campisi and Vijg, 2009)

 

Extracellular matrix stiffening, extracellular aggregates, intracellular aggregates are still very much on the table. So are senescent cells, because the "epigenetic "clock"" is not a measure of cell senescence or mitotic age (from another of the papers on Mittledorf's blog). Epigenetic reprogramming won't help with mitochondrial damage either. And so on.

 

Basicaly the only strand of SENS affected by these epigenetic theories is the regenerative strand. But that's also the strand SENS have the least interest in considering it's already quite well funded and researched by the mainstream - and the same people working on stem cells are working on epigenetic reprogramming as well so really, I don't think the SENS foundation will be severely interested to take part in the research either way.

 

The easiest way to know for sure is to contact someone from SENS and asking them directly about it.

 

corb... I'm glad that I pressed this question and glad you have provided an answer that makes sense, at least to me. Thank you.