Monday, July 9, 2007

Life: The Long View

Aging and our new prospects for longevity.


Had you been born in the year 1850, no one would have expected you to live much past the age of 38. The life expectancy of a newborn in 1925 was still only 57 years. Today, our young ones may live well past the projected average age of 78.

Those are some terrific leaps in life expectancy, and the extra years represent the ultimate gift of modern medicine. Researchers are now on the cusp of therapies to extend our lives ever longer.

The Road Keeps Getting Longer

Remember that no one dies of old age; we die of diseases. Earlier extensions in life-span averages came thanks to antibiotics, advances in medicine and better health programs. In addition to curbing "early mortality," science also has helped us affect late mortality by making it possible to live with or even beat diseases like cancer.

Life-span extension has been on the radar of the scientific community for only 15 to 20 years. And during the past 10 years we've seen quantum leaps due to a better understanding of genetics. "Aging stopped being something that happens to us and started being something we could not only describe but actually understand the molecular basis of," says Dr. Felipe Sierra, director of the Biology of Aging program at the National Institute on Aging (NIA). Sierra's program funds most of the basic biological research on longevity.

Greetings, SIR2

One researcher on the path is Dr. Lenny Guarente, professor of biology at MIT and author of Ageless Quest: One Scientist's Search for Genes That Prolong Youth. Building on earlier yeast studies, Guarente and fellow researchers found eight years ago that a gene called SIR2 could extend life span in roundworms.

He explains in simple terms, "If, by genetics, you move an extra copy of the SIR2 gene into a host—whether it's a roundworm, yeast or a fruit fly—the host lives longer. Conversely, if you knock the gene out, they live shorter."

Mammals have seven SIR2-like genes now known as sirtuins, and Guarente believes this gene pathway may provide the key to governing longevity in mammals. "The one sirtuin everyone is interested in now, the top dog, is SIRT1," Guarente says. "It's hard to believe that one gene could be so dominant in something like aging, but SIRT1 is shown to do so many important things in cells. It's just counterintuitive that something would have broad benefit against several diseases." But SIRT1 and its sirtuin brethren appear to pack a powerful punch.

A True Silver Bullet?

Granted, it's a long way up the life-form chain from roundworms to mice (the first mammals being tested) to people. But all mammals share the sirtuin gene set, and these genes appear to be responsible for preserving the lives of cells.

So, here's where it gets exciting: Eventually we may be able to create a drug that mimics how sirtuins protect cells. Medical professionals are famously skeptical about identifying "silver bullet" solutions, but some scientists believe that such a drug would do for age-related diseases what statins have done for lowering cholesterol. "The challenge for us is going to be to develop drugs that are effective and safe," says Guarente. "I think it's in the cards. I think it's going to happen."

Calorie Restriction

At first blush, calorie restriction sounds like a reasonable and simple anti-aging technique: Reduce calories to be healthier and therefore live longer. That's the same dietary advice we've been getting for years. But the geneticists studying it are not just saying you should cut back on the Ding Dongs. Restricting calories is what helps the sirtuin genes preserve cell life. The silver-bullet drug essentially would "trick" the cells into thinking they had been calorie-restricted.

Why use a drug instead of changing your diet? It's possible to limit your intake to about 1,000 calories per day, but that raises a couple of issues: a) drastically restricting your diet can lead to malnutrition and being underweight, both of which are associated with their own life-threatening conditions; and b) only 1,000 calories per day? Good luck with that.

Long Story Short

Research on calorie restriction and sirtuins is at the forefront of longevity studies today. Here's a quick glance at other current theories and therapies.

Insulin and insulin-like growth factor (IGF) signaling may explain how the prevention of obesity-related disorders helps leaner people live longer.

Apoptosis and senescence have been studied for several years in other contexts. The role of apoptosis ("cell suicide") and senescence (loss of a cell's power to regenerate) in maintaining cellular equilibrium has come back into focus for longevity research.

Adult stem cells may provide a means to repair or replace damaged cells (or cells lost to apoptosis or senescence) that play a role in disease and aging.

All of these pathways provide hope for extending life in the coming decades. In the meantime, eating well, exercising and maintaining a healthy state of mind will always be fundamental to enjoying a good, long life.

By Rich Maloof for MSN Health & Fitness

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