Re: New pill may help turn on anti-aging defenses

[Guest guest]

Might taking a pill help turn on anti-aging defenses? The Reuters report below and the free full-text paper suggest maybe that it may be true, although the connection between the gene-- SIRT-- and a pill may be confusing. http://www.msnbc.msn.com/id/20890453/ Pill may help turn on anti-aging defensesMedication may fight multiple diseases at once, researchers say ReutersUpdated: 10:50 a.m. PT Sept 20, 2007WASHINGTON - Researchers said on Thursday they had found more ways to activate the body's own anti-aging defenses — perhaps with a pill that could fight multiple diseases at once. Their study, published in the journal Cell, helps explain why animals fed very low-calorie diets live longer, but it also offers new ways to try to replicate the effects of these diets

using a pill instead of hunger, the researchers said. "What we are talking about is potentially having one pill that prevents and even cures many diseases at once," said Sinclair ... http://tinyurl.com/2ym68n Nutrient-Sensitive Mitochondrial NAD+ Levels Dictate Cell SurvivalHongying Yang, Tianle Yang, ph A. Baur, , Takashi Matsui, J. Carmona, Dudley W. Lamming, Nadja C. Souza-Pinto, Vilhelm A. Bohr, Rosenzweig, de Cabo, A. Sauve, and A. SinclairCell, Vol 130, 1095-107, 21 Sept 2007 Summary A major cause of cell death caused by genotoxic stress is thought to be due to the depletion of NAD+ from the nucleus and the cytoplasm. Here we show that NAD+ levels in mitochondria remain at physiological levels following

genotoxic stress and can maintain cell viability even when nuclear and cytoplasmic pools of NAD+ are depleted. Rodents fasted for 48 hr show increased levels of the NAD+ biosynthetic enzyme Nampt and a concomitant increase in mitochondrial NAD+. Increased Nampt provides protection against cell death and requires an intact mitochondrial NAD+ salvage pathway as well as the mitochondrial NAD+-dependent deacetylases SIRT3 and SIRT4. We discuss the relevance of these findings to understanding how nutrition modulates physiology and to the evolution of apoptosis. ... ... D.A.S. and A.A.S. are consultants to Sirtris Pharmaceuticals, a company aiming to treat diseases by modulating sirtuins. D.A.S. is a cofounder of Sirtris Pharmaceuticals and sits on their advisory board and board of directors. After completing this study, H.Y. became an employee and shareholder of Sirtris Pharmaceuticals. -- Al Pater,

alpater@...Dave <davemaddux@...> wrote: link: http://www.msnbc.msn.com/id/20890453/full text:Pill may help turn on anti-aging defensesMedication may fight multiple diseases at once, researchers sayReutersUpdated: 10:50 a.m. PT Sept 20, 2007WASHINGTON - Researchers said on Thursday they had found more ways toactivate the body's own anti-aging defenses — perhaps with a pill thatcould fight

multiple diseases at once.Their study, published in the journal Cell, helps explain why animalsfed very low-calorie diets live longer, but it also offers new ways totry to replicate the effects of these diets using a pill instead ofhunger, the researchers said."What we are talking about is potentially having one pill thatprevents and even cures many diseases at once," said Sinclair, apathologist at Harvard Medical School who helped lead the research.Sinclair helped found a company that is working on drugs based on thisresearch, Sirtris Pharmaceuticals.The key is a family of enzymes called sirtuins. They are controlled bygenes called SIRT1, SIRT2 and so on.Last year, researchers showed that stimulating SIRT1 can help yeastcells live longer.Sinclair, working with colleagues at his company, at CornellUniversity in New York and the U.S. National Institutes of Health,identified the

actions of two more sirtuin genes called SIRT3 and SIRT4.They found the enzymes controlled by these genes help preserve themitochondria — little organs inside of cells that provide their energy."These two genes, SIRT3 and SIRT4, they make proteins that go intomitochondria. ... These are little energy packs inside our cells thatare very important for staying healthy and youthful and, as we age, welose them and they get less efficient," Sinclair said in a videotapedstatement."They are also very important for keeping the cells healthy and alivewhen they undergo stress and DNA damage, as we undergo every dayduring the aging process."Sinclair and colleagues have found in other studies that even if therest of a cell is destroyed — the nucleus and other parts — it canstill function if the mitochondria are alive.His team found that fasting raises levels of another protein calledNAD. This, in turn,

activates SIRT3 and SIRT4 in the mitochondria ofthe cell and these help keep the mitochondria youthful."We've reason to believe now that these two genes may be potentialdrug targets for diseases associated with aging," Sinclair said."Theoretically, we can envision a small molecule (pill) that canincrease levels of NAD, or SIRT3 and SIRT4 directly, in themitochondria. Such a molecule could be used for many age-relateddiseases," he added."Diseases like heart disease, cancer, osteoporosis — even things likecataracts. What we are aiming to do is to find the body's naturalprocesses that can slow down aging and treat these diseases."Sirtris is already working on such drugs. It has an experimental pillcalled SRT501, which it is testing in Phase 2a trials in patients withtype-2 diabetes."These exciting new data further validate sirtuins as attractivetargets for drug development to treat diseases of

aging," Dr.Christoph Westphal, chief executive officer of Sirtris, said in astatement.Copyright 2007 Reuters Limited. All rights reserved. Republication orredistribution of Reuters content is expressly prohibited without theprior written consent of Reuters.URL: http://www.msnbc.msn.com/id/20890453/

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[Guest guest]

Just 48 hours of fasting provides protection against cell death. The

loss of appetite that accompanies many illnesses may be an automatic

protective mechanism. The onset of protection occurs fairly quickly

and may explain the benefits reported for intermittent fasting.

Tony

" Rodents fasted for 48 hr show increased levels of the NAD+

biosynthetic enzyme Nampt and a concomitant increase in mitochondrial

NAD+. Increased Nampt provides protection against cell death and

requires an intact mitochondrial NAD+ salvage pathway as well as the

mitochondrial NAD+-dependent deacetylases SIRT3 and SIRT4. "

===

link:

http://www.msnbc.msn.com/id/20890453/

>

>

> Pill may help turn on anti-aging defenses

>

> Medication may fight multiple diseases at once, researchers say

> Reuters

> Updated: 10:50 a.m. PT Sept 20, 2007

>

> WASHINGTON - Researchers said on Thursday they had found more ways to

> activate the body's own anti-aging defenses — perhaps with a pill that

> could fight multiple diseases at once.

>

> Their study, published in the journal Cell, helps explain why animals

> fed very low-calorie diets live longer, but it also offers new ways to

> try to replicate the effects of these diets using a pill instead of

> hunger, the researchers said.

>

> " What we are talking about is potentially having one pill that

> prevents and even cures many diseases at once, " said Sinclair, a

> pathologist at Harvard Medical School who helped lead the research.

>

> Sinclair helped found a company that is working on drugs based on this

> research, Sirtris Pharmaceuticals.

>

> The key is a family of enzymes called sirtuins. They are controlled by

> genes called SIRT1, SIRT2 and so on.

>

> Last year, researchers showed that stimulating SIRT1 can help yeast

> cells live longer.

>

> Sinclair, working with colleagues at his company, at Cornell

> University in New York and the U.S. National Institutes of Health,

> identified the actions of two more sirtuin genes called SIRT3 and SIRT4.

>

> They found the enzymes controlled by these genes help preserve the

> mitochondria — little organs inside of cells that provide their energy.

>

> " These two genes, SIRT3 and SIRT4, they make proteins that go into

> mitochondria. ... These are little energy packs inside our cells that

> are very important for staying healthy and youthful and, as we age, we

> lose them and they get less efficient, " Sinclair said in a videotaped

> statement.

>

> " They are also very important for keeping the cells healthy and alive

> when they undergo stress and DNA damage, as we undergo every day

> during the aging process. "

>

> Sinclair and colleagues have found in other studies that even if the

> rest of a cell is destroyed — the nucleus and other parts — it can

> still function if the mitochondria are alive.

>

> His team found that fasting raises levels of another protein called

> NAD. This, in turn, activates SIRT3 and SIRT4 in the mitochondria of

> the cell and these help keep the mitochondria youthful.

>

> " We've reason to believe now that these two genes may be potential

> drug targets for diseases associated with aging, " Sinclair said.

>

> " Theoretically, we can envision a small molecule (pill) that can

> increase levels of NAD, or SIRT3 and SIRT4 directly, in the

> mitochondria. Such a molecule could be used for many age-related

> diseases, " he added.

>

> " Diseases like heart disease, cancer, osteoporosis — even things like

> cataracts. What we are aiming to do is to find the body's natural

> processes that can slow down aging and treat these diseases. "

>

> Sirtris is already working on such drugs. It has an experimental pill

> called SRT501, which it is testing in Phase 2a trials in patients with

> type-2 diabetes.

>

> " These exciting new data further validate sirtuins as attractive

> targets for drug development to treat diseases of aging, " Dr.

> Christoph Westphal, chief executive officer of Sirtris, said in a

> statement.

> Copyright 2007 Reuters Limited. All rights reserved. Republication or

> redistribution of Reuters content is expressly prohibited without the

> prior written consent of Reuters.

>

> URL: http://www.msnbc.msn.com/id/20890453/

>