LONGECITY

Not sure what to make out of this yet (need to ponder over it to grasp fully the experiment/result) but it seems the steps are getting wider and faster and the experiments more and more interesting, when it comes to "hacking" the transcription factors and stuff like that (and once again - the "damage" we talk about is more likely a "damage to the pattern of gene expressions". Correct me if I'm wrong.)..

http://www.wired.com...lar-senescence/

Between the lung rejuvenation study, the stem cell activation in the elderly, and this research, it has been a great week for longevity/rejuvenation science.

One part of the Wired article that was confusing to me is this part:

Baker’s team, led by himself and Mayo Clinic gerontologist Jan van Deursen, started by engineering a mouse strain that aged unnaturally fast. When they inactivated p16 and other senescence-linked genes in embryonic mice, aging proceeded normally.
It hinted at the importance of cellular senescence, but wasn’t so convincing as if the mice had senesced over the course of their lives, then been treated. To accomplish this, Baker and van Deursen designed a fast-aging mouse strain that would, upon receiving a drug trigger, expel p16-producing cells from fatty tissues, muscles and eyes.

So when they inactivated P16 and related genes, the fast aging mice, aged at their normal fast pace? Then when they used a drug trigger to get rid of senescent cells, the fast aging mice did not age as fast? Is that correct?

The treatment:
-Prevented cataracts
-Delayed muscle loss
-Increased preservation of fat tissue
-Increased energy output!
-Prevented hunchback spine condition (lordokyphosis)


This is pretty incredible stuff. This is a MAJOR vindication of SENS, as removing senescent cells is essentially apoptoSENS.


Interestingly mice died from heart failure. Check graph C out and it might explain why (Very low relative expression of their gene in the heart cells - what would have happened if more senescent cells were removed from the heart? Maybe good maybe bad.):


Edited by Elus, 02 November 2011 - 09:58 PM.

http://www.bbc.co.uk...health-15552964

Isoprinosine comes to mind, for humans.

Do you have more info on that?

I thought Saikosaponin A, but I would need to test it of course.

A

Link to the nature article here
Clearance of p16^Ink4a-positive senescent cells delays ageing-associated disorders

http://www.nature.co...ature10600.html

Thanks Max,

Now that I see it, i understand that it may not be done the way I originally thought.
The study is in the members only area.

Cheers
A

http://www.bbc.co.uk...health-15552964

Another part of the SENS program appears to be taking shape. A long. Way to go though

The link does not appear to work. Do you mean the same thing as this? http://www.dailymail...o=feeds-newsxml

It says in the article that the researcher claimed "Young people were already clearing out their senescent cells" and if you can "boost the immune system a bit to make sure the senescent cells are removed", it might halt aging significantly. So how does that tie in with what we already know? Does he want to say that young people who take antioxidants etc are already well on their way to halting their aging? I just want to interpret this article in a way that will alllow me to do more beneficial things before the drug that has this dramatic improving effect is available. What does it say - that we should do more to boost the immune system? Which is what? Which supplements help out most at clearing out the old cells?

The link does not appear to work. Do you mean the same thing as this? http://www.dailymail...o=feeds-newsxml

Link works for me, but it does not appear to be the same thing as the daily mail article.

Link works for me, but it does not appear to be the same thing as the daily mail article.

Probably along the same lines though...been quite a bit of coverage as is fitting for something so exciting.

Speaking of P16 ...aren't there a few supplements out there that affect it.

That reminds me, I think I've been here long enough, I should probably get around to joining..

Isoprinosine (echinacea) would uprate T-lymphocyte production and may facilitate this effect in humans.

but what do we get from this. the bbc article says apart from the tests on mice that young people NOW are cleaning their senescent cells out - do they say its the antioxiants people are taking or what?

http://the-scientist...-advance-aging/

Old Cells Advance Aging

By selectively killing senescent cells, researchers can slow the
decline of health in aging mice.

By Tia Ghose | November 2, 2011

Researchers have been able to delay the onset of age-related health
declines in mice by selectively killing off aging cells, suggesting
that cellular senescence can actively causing damage to surrounding
tissue. The findings, published today (November 2) in Nature, could
one day be used to create anti-aging therapies.

“It’s been speculated for some time that these senescent cells are a
major cause of what goes wrong with aging,” said molecular and cell
biologist Judith Campisi of the Buck Institute for Research on Aging
in Calif., who was not involved in the study. “So this is really a
very important step forward in validating that hypothesis.”

Indeed, researchers have long recognized the role of senescent cells—
aging cells which no longer divide—in the health decline that
accompanies aging, such as muscle weakness, heart problems, cataracts,
and other ailments. But it wasn’t clear whether aging cells cause harm
because they actively secrete inflammatory molecules such as
cytokines, or whether they were simply dead weight, harmful because
they had lost their normal cellular functions, said Norman Sharpless,
a gerontologist and oncologist at the University of North Carolina at
Chapel Hill, who was not involved in the study.

To answer this question, cancer biologist Jan van Deursen of the Mayo
Clinic and his colleagues developed a clever test. Senescent cells,
which often harbor genetic damage, secrete a tumor suppressor molecule
called p16. Van Deursen and his team created mice that age
prematurely, falling prey to a variety of age-related diseases early
in life. They also inserted a gene into the mouse genome, which
allowed them to selectively kill cells expressing p16 by feeding the
mice rosiglitazone, a common diabetes drug.

Mice fed a diet containing rosiglitazone from infancy took much longer
to develop muscle weakness, cataracts, and other signs of aging than
controls. Even when older mice were fed rosiglitazone, many of the age-
related problems plateaued. The findings suggest that senescent cells
actively cause harm, and that killing them can delay at least some
forms of aging. “If you translate that to humans, if you were to clear
senescent cells regularly from a young age, that would probably have a
major impact on health span,” van Deursen said.

Selectively killing off p16 didn’t slow all forms of aging, however.
The treatment had no effect on the unusually high rates of heart
disease seen in the mice. As a result, most mice still died of heart
problems and the overall lifespan of the mice didn’t increase. In
addition, the study looked at rapidly aging mice, but the researchers
need to confirm that the same benefits occur in naturally aging mice,
Campisi said.

Still, the study suggests a potential pathway for delaying aging in
humans, Sharpless said. If cytokines and other inflammatory signals
are the root of senescent cells’ adverse effects, “it’s not difficult
to make drugs that interfere with [such signaling].” The trick would
be determining which signals to target and ensuring that they don’t
have undesirable side-effects, such as lessening people’s immune
response to infection, he said.

D. J. Baker et. al, “Clearance of p16-Ink4a-positive senescent cells
delays ageing-associated disorders,” Nature, doi:10.1038/nature10600,
2011.

Just read the Nature paper and discussed it with one of my profs who appeared to have read it yesterday. The study however found no increase in lifespan but this could be because the mice model causes heart failure and the artificial construct is not expressed in the heart. The study indeed is interesting because it provides evidence that senescent cells at least causes diseases in 3 different tissues and that the removal of these cells can prevent and attenuate the progression of these diseases. The sad part of the study is that they use an 'accelerated'-aging mice model. The next step will be to try it in normal mice or rats. One other limitation is that the study used a genetic construct and we cannot use that in humans. So, for humans we will have to find alternative solutions like discovering which part of the metabolism of these cells that we can interfere with that kills them without killing normal cells. My prof. brought up the question as to why senescence exists in the first place. Maybe killing the cells could do more harm than good (inflammation?).

Has it not been reported somewhere that astragalus and astragalus extracts promots apoptosis?

those were not ordinary mice more experiments are underway

http://www.startribu.../133130703.html
Edited by ihatesnow, 03 November 2011 - 09:18 PM.

The drug used was Rosiglitazone, a PPARy activator and down regulator of IGF-1, used for sensitizing insulin in the treatment of diabetes. Increased incidence of heart disease is a known side effect but I can't seem to find out why. Some other non-prescription PPAR activators off the top of my head include calorie restriction, strength and endurance training and tocotrienols.

Has anyone seen this yet?

http://www.google.co...o31GONlBYspa2Qw

I just posted this study in the bioscience section.

So, can we activate P16 and hope to get a some of the same effects? Anthony, do think it's time to try to make a product that can possibly even more potently activate P16 more than the one you guys have now?

In the study, they activated gene P 16 in order to trigger the killing off of senescent cells, correct???

Anyone have access to the study?

I just posted this study in the bioscience section.

So, can we activate P16 and hope to get a some of the same effects? Anthony, do think it's time to try to make a product that can possibly even more potently activate P16 more than the one you guys have now?

In the study, they activated gene P 16 in order to trigger the killing off of senescent cells, correct???

From what I read, P16 becomes more prominent in aging and is the result of more senescent cells. Less P16, less senescent cells. However, from what I read this research is in it's infancy, and they are concerned that wiping out P16 may open up the potential for cancer cells, tumors to form and continue to grow. It is a good concept, but far from being totally understood.

Speaking of P16 ...aren't there a few supplements out there that affect it.

Yeah, anyone know which ones? I'm intrested in what thi reseach can tell us as to what to do now. What clkears out old cell junk best?

Activating P16 wouldn't do anything for you; it might even be bad. What you have to do is figure out a way to kill the cells that are expressing P16INK4a.

I'd question whether activating tumor suppressor genes is really a good idea. They suppress tumors by triggering the apoptotic cascade. If you can selectively trigger apoptosis in senescent cells, that's great, but I don't think we have any compounds that do this as of yet. You wouldn't want to kill off healthy cells in an attempt to upregulate p16 expression.

Furthermore, activating tumor suppressors can dampen the replicative ability of cells, and you don't want to do this to immune cells which undergo clonal expansion. You may essentially prevent your immune system from adequately responding to pathogens.
Edited by Elus, 04 November 2011 - 02:30 PM.

Activating P16 wouldn't do anything for you; it might even be bad. What you have to do is figure out a way to kill the cells that are expressing P16INK4a.

Haha niner, I just posted almost that same exact response in the other thread about this. Can you use your mod magic to fuse these threads?
Edited by Elus, 04 November 2011 - 02:34 PM.