Longevity pill on the horizon?
July 10, 2009 by Leila Gray(PhysOrg.com) -- While applauding findings that an Easter Island compound extends the lives of middle-aged mice, University of Washington longevity researchers caution that healthy people shouldn't start taking the drug in the hopes of extending their own life spans -- at least not yet.
UW scientists Dr. Matt Kaeberlein, assistant professor of pathology, and Dr. Brian Kennedy, associate professor of biochemistry, study factors that control aging. They were asked by Nature to write a commentary on a paper published in the July 9 issue showing that dietary supplementation with rapamycin increases the life span of mice. They observed that, until recently, compounds that slow the hands of time were in the realm of science fiction, but with this finding may be closer to reality.
"The possibility that such compounds might exist, and might perhaps even be within reach," they wrote, "has gained scientific credibility."
Their News & Views editorial, "Ageing: A Mid-Life Longevity Drug?" noted that the study, co-led by Dr. David Harrison at the Jackson Laboratories in Maine, Dr. Richard Miller at the University of Michigan, and Dr. Randy Strong at the University of Texas Health Sciences Center at San Antonio, used a specially formulated, time-release rapamycin supplement in their laboratory mouse chow. Interestingly, the mice were not exposed to rapamycin in the diet until they were middle-aged, or, as the study reported, "roughly the equivalent of a 60-year-old person." Even so, the drug had a profound effect on lifespan.
Rapamycin was originally discovered in soil samples on Easter Island (Rapa Nui), famous for its towering, long-faced, stone Moai statues. Rapamycin already has a clinical role in reducing rejection of transplanted organs, in treating advanced kidney cancer, and in preventing narrowing of the heart's arteries after corrective surgery.
The study of rapamycin's longevity effects was part of the National Institute on Aging Interventions Testing Program. It accepts nominations for compounds from members of the scientific community, and selects the most promising to undergo parallel testing at three different institutions. Several compounds have been tested, but rapamycin is the first to significantly increase lifespan at all three centers in both male and female mice.
Rapamycin, which Kaeberlein, Kennedy and Dr. Stanley Fields, professor of genome sciences, had previously shown increases life span in yeast, is know to inhibit an enzyme called TOR. TOR activity is regulated by nutrient availability. Prior work by these UW scientists indicated that reducing TOR activity is central to how dietary restriction slows aging in yeast. Dietary restriction has long been known to slow aging in mice and to protect animals against age-related disorders like cancer, obesity, and heart disease. In the commentary, the authors suggest that the possibility that rapamycin is mimicking the effects of dietary restriction in mice merits further study.
The commentators also warn that healthy people shouldn't take rapamycin to slow aging because it can suppress the immune system. However, they don't rule out the possibility that rapamycin -- or more sophisticated interventions to reduce TOR activity -- might someday prove useful against age-related diseases. They also speculate that drug strategies might be discovered in the relatively near future to provide similar disease-fighting and longevity benefits without unwanted side effects.
The authors concluded: "Although extending human lifespan with a pill remains the purview of science fiction for now, the results of the study by Harrison and his colleagues provide reason for optimism that, even during middle age, there's still time to change the road you're on."
Provided by University of Washington (news : web)
Jul 08, 2009 |
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Death is not a fluke or an accident it's an outcome of a carefully planned and executed program. Our lifespan is carefully optimized and encoded in our genes, it's the price we pay for evolution. The clock uses energy consumption as this is the most reliable measure of lifespan available at the cellular level. We die to make room for future generations.
In the molecular arms race of life immortality means extinction.
So far the only candidate for a clock seems to be telomeres. Which is not energy consumption although I suppose you could say it was related since it IS related to the number of times a cell has divided.
Ethelred
There are other candidates like accumulation of damaged proteins or DNA circles for example but we don't yet know enough to pinpoint the clock at the molecular level.
The statement which you quoted is based on a number of observations: 1. the universal occurrence of calorie restriction based longevity 2. genes associated with longevity which are shared between distant eukaryotic species are often those linking nutrient sensing to protein expression 3. energy consumption is the best way to judge how far a cell is along the "program of life" since the actual time it takes to generate offspring depends strongly on nutrient availability, energetic cost of generating offspring is much less variable.
Telomeres are more likely an additional protection against transformation of somatic cells in mammals (and probably other multicellular organisms) then a true lifespan clock, yeast for example maintain stable telomeres throughout lifetime yet they do also age and die.
While these certainly count as damage I don't see that as being a clock.
Where I am coming from on this:
A number of people have claimed(wellover a decade ago)that there was no known clock because the cell lines in animals all age at different rates. For instance the immune system and skin cells appear to begin to fail earlier than other lines.
At that time it had only recently been discovered that human cells, in vitro, could only divide so many times (around fifty)before they began to fail.
Later experiments showed that the older the cell donor the fewer the divisions there would be. For example cells from a 70 year old donor might only divide 20 times.
This showed that, despite the claims of some that there was no overall clock, there might very well be such a clock.
Experiments with cancerous cell lines showed that they did not stop dividing. These experiments were mostly if not entirely done with cancer cells from Henrietta Lacks.
http://en.wikiped...iki/HeLa
Her cancer lives on long after her death.
This line of research lead to the discovery that telomeres get shorter with each division in mammals. Obviously this is not the case for all cell types, stem cells in particular.
This makes telomeres look very much like a cellular clock. Not in this sense of a clock ticking at a regular rate but more as count of the number of the divisions. To many, me included, this looks like the telomeres may do a number of things. For one stopping out of control mutated cells. Almost all cancer cells have telemorase activated which resets the length of the telomeres.
In any case the when the telomeres get very short or at least after the telomer is completely gone cells stop dividing. A good thing with tumors but a bad thing if you want to go on living.
Well yeast are single celled. It is interesting that they even have telomeres. I wouldn't have expected it although if it started with eukaroytes then it makes sense.
Searching I see that plants, fungi and amoeba all have telomeres. Well maybe its some amoeba. I finding this search interesting now but I keep running into pay to read papers. So much for the Information Wants To Be Free rubbish.
Interesting:
Fits my thinking that life started with RNA protein compounds rather than DNA or RNA or proteins. Gosh its nice to find a hypothesis might hold water.
Now this gets to the point or at least where I was wandering off too.
http://delangelab...RMCB.pdf
So it looks to me like most but not all eukaryotes uses telomeres.
Ethelred
If that's true, then any broad-based pill that seeks to extend telomeres or slow their degradation would result in longer life but an increased number of cancerous tumors.
I wonder if they've already discovered such a substance but classified it as a potent carcinogen.
Also there is that matter of tumors. Cells more likely to go out of control would need shorter shorter telomeres to cut down on out of control growth.
This is stuff I have read over the years. It may have a high level of crap as I have never taken a biology class and my last formal classes were in the 70's in any case. I do have a biochemistry textbook laying around here but its from the late 90's and I have only glanced at a few parts. Primarily about the ribosomes as I am interested in how life got going.
Ethelred