Doc, got anything to make me immortal?

They're working on it, and the average life span just went up another 72 days. Here's a survey of some current scientific approaches to reversing aging.
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UW's Matt Kaeberlin is optimistic about longevity research

They're working on it, and the average life span just went up another 72 days. Here's a survey of some current scientific approaches to reversing aging.

Life expectancy touched a new high again, according to just-released figures [PDF]. We picked up about another 72 days, bringing the grand total to 77.9 years, quite a bit shy of immortality. How far can human life span be stretched by the exertions of science and technology? And could researchers maybe hurry a little?

The modern project to satisfy longings for the eternal originates in the medieval period. Monkish asceticism — eating little and not reproducing — is the one true way to a longer life, at least in lab animals. Rhesus monkeys fed 30 percent fewer calories than a control group over the last 20 years appear to live longer, healthier lives. The effects of calorie restriction (CR) on humans aren'ꀙt known. But CR is no party. It usually reduces fertility. Rhesus macaques on restricted diets resort more to cocaine, heroin, and other drugs, given the chance. Humans on CR smoke more.

What could be more perfect than a pill that mimicked calorie restriction without the decades of gnawing hunger and untoward side effects? Resveratrol, the magic ingredient found in red wine, extends the lives of yeast, worms, and flies — but, sorry, not mice. (You can still enjoy the relentless internet ads for Resveratrol, though.) Last month, however, a different study concluded that the drug Rapamycin does increases life span, an impressive 14 percent in female mice and a slightly less generous 9 percent in males. Instead of a lifetime of CR self-punishment, mice ate as they pleased and only started on Rapamycin at what would be the equivalent of 60 years old in humans. Just a week after the Rapamycin result, scientists found a pair of proteins which together extend lifespan in worms by as much as 20 percent. These two potential breakthroughs were reported not in fringe longevity publications but the preeminent science journal, Nature.

Lab-grown organs already have aging backpedaling. In 2006, researchers grew bladders from a patient'ꀙs own cells. The resulting implants checked out fine earlier this year, and more trials are on the way. In another milestone, in late 2008, researchers developed and implanted an airway (a trachea) which included the patient'ꀙs own stem cells to enhance regeneration. Tissue engineers can now grow thin sheets of cardiac muscle from stem cells and envision grafting these to areas damaged by heart attack, perhaps a first step toward growing a complete organ.

Let'ꀙs all live until the 22nd century, shall we? That'ꀙs too modest an ambition for some. In two weeks, longevity researchers will convene to hone 'ꀜStrategies for Engineered Negligible Senescence,'ꀝ meaning ways to make humans immortal. It'ꀙs the fourth such gathering. But there will need to be many, many more.

Remarkably, no one yet agrees on what aging is or what causes it. And although we'ꀙve been stretching the lives of CR-thinned animals since 1935, we still don'ꀙt understand how calorie restriction works or whether it does in humans. A recent study of humans showed that the restricted protein of a vegan diet, not reduced calories, triggered the chemical cascade that increased longevity in lab animals.

Still, scientists seem to be on to something fundamental. The mechanisms that extend life by under-nutrition might also shorten life when over-nutrition reigns. Type-2 diabetes from obesity accelerates many age-related conditions like heart disease. Not surprisingly, anti-diabetes drugs have been tried as anti-aging agents. More than a quarter century ago, Phenformin increased lifespan a hefty 21 percent in lab mice, a bigger bang than Rapamycin. In humans, however, Phenformin has potentially fatal side effects, and the drug has been withdrawn.

The knob or knobs turned by calorie restriction, diabetes, and various drugs appear to be connected to tiny signals affecting supremely basic cell functions — like growth. Doing better than the factory settings might be daunting. Matt Kaeberlin, a scientist at the University of Washington, believes the Rapamycin findings are highly portentous. But he points out, 'ꀜWe have cured cancer a hundred times in mice — but not in humans.'ꀝ The human genome provides no obvious handholds for clambering to greater heights of longevity. Searches for 'ꀜlongevity genes'ꀝ in the DNA of people living beyond 90 turned up remarkably little. And genes that regulate aging are scattered widely over the genome and might number in the thousands.

Stem cell therapy and tissue engineering, however, are genuinely promising. It seems like researchers will soon make stem cells from belly button lint. But the breakthroughs obscure continued mysteries of how stem cells work and how to keep them from becoming the wrong kind of cell. Although we dream of curing paralysis, today the sole stem cell therapy to reach clinical trials treats only severely bruised spinal cords. In mice with the same condition, just injecting stem cells somehow restored a more normal walking pattern, although short of a 100 percent recovery. (This trial was just delayed, perhaps from safety concerns.)

It is still early for these methods, but meeting the specs of the original equipment will be challenging. Those sheets of cardiac muscle grown from stem cells are currently too thin and diaphanous to earn the name of tissue. And muscle grown in a petri dish is currently not as strong as the organically grown variety.

The future looks good, but as Martin Birchall, who led the team performing the regenerated trachea transplant, put it: 'ꀜWe certainly don'ꀙt want to get ahead of ourselves.'ꀝ The commendably restrained Birchall believes 'ꀜwe will be in a position to use regenerative medicine in the widest sense to repair most things in due course, but this could take 20-30 years.'ꀝ Remarkably, Birchall doubts whether engineered organs will be able to surpass transplanted ones. Even the humble larynx must perform multiple, near-opposing tasks like coughing and swallowing. Supplied by more fine motor control fibers than any other part of the body, the larynx makes possible speech, smelling, tasting'ꀔeven kissing.

Won'ꀙt accelerating technology make today'ꀙs mountainous obstacles seem like nano-bumps in the rear view mirror? Birchall answers that, at least for regenerative medicine, 'ꀜprogress will be slow, with occasional step-changes.'ꀝ Broader medical progress, as measured by the rate of new drug introductions, is neither exponential nor accelerating. The number of new drugs approved fell from 53 in 1996 to 17 in 2002, and has averaged about 21 each year since. Suggestive of the current range of medical power, science has produced a pill for erectile dysfunction but not for the more difficult (but still far from fatal) age-related disorder, balding.

Science is unequivocal, however, concerning diet and exercise. Obesity ages you the equivalent of ten years in terms of heart attack risk. Use this year'ꀙs longevity winnings to enjoy a walk — and appreciate the larynx.


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