Monday, August 27, 2007


Well -- it's that time of year in Delhirium when all normal people turn their thoughts to the warm and wonderful subject of ... mortality! Yep. The end of the monsoon, that period between the rains and winter, when the atmosphere is soupier than the water in which naive young frogs get boiled to death*(*okay, so you don't know what I'm referring to? It's that old cautionary tale in which you throw a frog into a pot of boiling water and watch it jump right out. But throw it into a pot with room temperature water, then slowly turn up the heat and ... it'll get cooked before it can save itself)(side note: lab experiments have apparently disproved this rather cruel story).

SOoooo okay. Back to mortality. Or, as it turns out, IMmortality. There's a book with this catchy title -- HOW TO LIVE FOREVER OR DIE TRYING by Bryan Appleyard -- which suggests that immortality may not be such a far-fetched idea after all. This review from TIMES ONLINE is what got me thinking that I'd like to read the book.

NOT because I especially want to live forever. But then again ... maybe I'm just saying that coz I KNOW I won't? I mean, the methods discussed in the book are not likely to be available to people of my age and decrepitude but (according to the book's author) there may already be people alive now who will become eligible for the use of new technologies which will enable them to ward off death indefinitely. They wouldn't be immortal in the mystical sense -- i.e., a falling grand piano would put an end to their days as thoroughly as it would anyone else's days -- but at least they would not be succumbing to mere old age 'n' tumours.

I must say, it would be rather horrid to be living alongside jerks who, when you say something like "Well ... after all, all things come to an end .." can riposte with, SPEAK FOR YOURSELF, MICROBE!

But really: can you imagine what it might be like to live for ...oh ... 1000 years? One major casualty, it seems to me, would be temporal vows and promises. I mean, who would want to swear Eternal Love if there was the slightest chance a relationship would really last for more than 50 or 60 years? Imagine being stuck with the same spouse for 10 times the normal life span! Yow.

Diamonds would no longer be anyone's best friend ...


Anonymous said...

hi there microbe - trees live to be 1000 years old - californian redwoods - older than 2000 years is the current tree record i believe. so biological systems can reach 1000. humans? well the best case estimates are that we could stretch it and make 120. no one more than that has ever been recorded. the biggest hassle is that every time a cell divides billions of little little bits of info called genes (pronounced jeans! ok ok) need to be faithfully replicated - not an easy task and it always carries "errors" that inevitably take place - the metastasis of cancer and the aging process itself too - are believed to be rooted in this issue. scientists do say that after about 50 cell divisions - our DNA starts getting eroded at the ends and cells soon get wonky - and guys are of course trying to catch this mechanism. anyway, so far the fact is that calorific restriction - reducing the amount of calories you consume seems to lengthen lifespan -as proven conclusively in rodents and other creepy crawlies but never been shown rigorously enough in humans to date and so the q becomes - move on to eating grass and live to be 120 or go chicken biryani and to hell with it. gt

Marginalien said...

*speaking with mouth full of grass* Okay. So I'm eating all this grass and now I don't WANT to live at all!

Yup -- well -- the book apparently addresses some of these urgent questions we all have about how to be like Giant Sequoias or Bristle Cone Pines without having to switch out of the animal kingdom altogether. I haven't read the book and something tells me that I've probably already gleaned whatever real information there is to gain from it -- i.e., "Ummm ... some people are working on this problem RIGHT NOW. And -- in case you had any doubts -- your call is important to us."

gt said...

well obviously you got your mouth full of grass - so lets take a li'l advice from my younger son who was telling me the other day as i was slurping down a beer - a last one for the road and he piped in - "dad why drink and drive - when you can smoke and fly?..... teenagers these days... so the grass therapy might be food 4 thought huh? or maybe we now know what it means to say getting down to the grass roots .... 'k,'nuff. best wishes gt

gt said...

Eat (Less) to Live (Longer)
New study reveals why restricting calories may lead to longevity
By Nikhil Swaminathan
Scientists believe they have an idea of how caloric restriction diets lead to increased longevity.
Scientists have known for more than 70 years that the one surefire way to extend the lives of animals was to cut calories by an average of 30 to 40 percent. The question was: Why?

Now a new study begins to unravel the mystery and the mechanism by which reducing food intake protects cells against aging and age-related diseases.

Researchers report in the journal Cell that the phenomenon is likely linked to two enzymes—SIRT3 and SIRT4—in mitochondria (the cell's powerhouse that, among other tasks, converts nutrients to energy). They found that a cascade of reactions triggered by lower caloric intake raises the levels of these enzymes, leading to an increase in the strength and efficiency of the cellular batteries. By invigorating the mitochondria, SIRT3 and SIRT4 extend the life of cells, by preventing flagging mitochondria from developing tiny holes (or pores) in their membranes that allow proteins that trigger apoptosis, or cell death, to seep out into the rest of the cell.

"We didn't expect that the most important part of this pathway was in the mitochondria," says David Sinclair, an assistant professor of pathology at Harvard Medical School and a study co-author. "We think that we've possibly found regulators of aging."

In 2003 Sinclair's lab published a paper in Nature that described the discovery of a gene that switched on in the yeast cell in response to calorie restriction, which Sinclair calls a "master regulator in aging." Since then, his team has been searching for an analogous gene that plays a similar role in the mammalian cell.

The researchers determined from cultures of human embryonic kidney cells that lower caloric intake sends a signal that activates a gene inside cells that codes for the enzyme NAMPT (nicotinamide phosphoribosyltransferase). The two- to four-fold surge in NAMPT in turn triggers the production of a molecule called NAD (nicotinamide adenine dinucleotide), which plays a key role in cellular metabolism and signaling.

The uptick in NAD levels activates the SIRT3 and SIRT4 genes, increasing levels of their corresponding SIRT3 and SIRT4 enzymes, which then flood the interior of the mitochondria. Sinclair says he's not sure exactly how SIRT3 and SIRT4 beef up the mitochondria's energy output, but that events leading to cell death are at the very least delayed when there are vast quantities of the enzymes.

SIRT3 and SIRT4 are part of a family called sirtuins. (SIRT1, which helps extend cell life by modulating the number of repair proteins fixing DNA damage both inside and outside the cell's nucleus is also a member.) SIRT is short for sir-2 homologue—a well-studied protein that is known to extend yeast cell longevity. According to Sinclair, all of the mammalian SIRT genes (and their proteins) are possible drug targets for therapies aimed at extending life, as well as staving off age-related illnesses, such as Alzheimer's disease, cancers and metabolic disorders, like diabetes.

"I think SIRT3 is the next most interesting sirtuin from a drug development standpoint," Sinclair says. "It does protect cells, but there's growing evidence that it may mediate the benefits of exercise as well."

Sinclair's lab is now working on developing what he calls a possible "supermouse" with elevated levels of NAMPT to see if it lives longer and is more disease-resistant than normal mice.

Matt Kaeberlein, a pathologist at the University of Washington in Seattle, says that Sinclair's team has an interesting hypothesis connecting the mitochondria to longevity, but that it needs to be more directly tested in the context of dietary restriction. "If the NAMPT-overexpressing mice are long-lived and disease resistant, that will provide more support for this idea."
For his part, Sinclair is eager to see the results of his experiments with the supermouse. "Depending on how this mouse turns out," he says, "we may put NAMPT on the list of drug targets, as well."