The following article comes from the U.S. News ebook, How to Live to 100, which is now available for purchase.
Medicine's focus has long been on treating specific diseases. We have radiation treatments to combat cancer tumors, cholesterol-lowering drugs to stave off heart attacks, and insulin to control diabetes.
But imagine if there were a drug that would slow down the aging process itself, a drug that didn't just treat a single disease but instead targeted multiple diseases of old age at once? It may sound far-fetched, but that's precisely what longevity scientists are working hard to produce.
"It's not just that we're trying to make people live longer; we're trying to make people live healthier. This is an exciting time for research," says Felipe Sierra, director of the Division of Aging Biology at the National Institute on Aging.
Indeed, top-notch research labs are rolling out studies at a rapid rate, and a growing chorus of experts believe the advances being made will ultimately lead to a crop of drugs capable of extending healthy lifespans. Signs of progress are abundant in medical journals.
In a discovery that Science magazine hailed as one of the top 10 breakthroughs of 2011, researchers from the Mayo Clinic published results showing they could markedly delay the onset of age-related diseases in mice by killing off the rodents' senescent cells. Senescent cells have stopped dividing and accumulate as organisms age. Though seemingly dormant, they're not: Just as old cars in junkyards can leak oil for years, they emit harmful substances that appear to fuel many of the diseases that strike older people.
The researchers were working on mice bred to age prematurely, and they found that exposing the mice to a synthetic drug that attacked senescent cells cut down on muscle loss, cataracts, skin thinning, and other signs of aging. Their next step is to replicate their findings in additional populations of mice and other animals. "We're not there yet, but we're getting closer to doing clinical trials on people," says James Kirkland, director of the Mayo Clinic's Robert and Arlene Kogod Center on Aging and one of the scientists involved in the study. "There's so much promise."
And it's not just senescence research that is stoking excitement. Another team of scientists, this one led by Ronald DePinho at Harvard University, has managed to control the aging process by targeting specialized structures at the tips of chromosomes called telomeres. When the researchers genetically engineered mice to have short telomeres, mice aged prematurely. When they used gene therapy to lengthen telomeres the reverse happened. Decrepit, infertile mice with shriveled testes and diminished cognitive functioning began to bounce back. DePinho has estimated that overall, the mice went from being what was essentially ages 80 to 90 in human years to the equivalent of middle age in the course of the experiment.
Other scientists have found that feeding aging mice rapamycin—an immunosuppressant that's used to prevent organ rejection after transplants—can extend the lifespan of mice significantly. The drug seems to improve the functioning of mitochondria, structures that generate power for cells, and whose dysfunction previous research has shown is involved in numerous diseases of aging.
But what does this all mean for those of us without whiskers and a tail who want to up our chances of living past 100? "The thing to remember is that most of the breakthroughs in longevity research that you hear about on the news have their origins in basic research in animals," says Sierra. No matter how exciting they are from a scientific perspective, it could be decades before they start yielding anti-aging medications for the masses, he cautions.
Take calorie restriction, for example, another hot topic in longevity science. Numerous studies dating back to the 1930s have shown that cutting calories to near starvation levels can be a boon for animal longevity, and in the early 1990s scientists made the first in a series of announcements suggesting they had sorted out why.
The thinking was this: Calorie-restricted animals survived longer, in many cases 30 percent longer, because the process activated a family of genes that produce proteins called sirtuins, substances that directly altered the metabolic activity of cells in ways thought to stave off diseases of aging.
When a team of scientists from Harvard reported in 2003 that a compound in the skin of red grapes called resveratrol seemed to activate sirtuins—and caused obese and diabetic mice fed a high-fat diet to live longer—sales of red wine and resveratrol dietary supplements shot through the roof.
In recent years, however, snags in the science have suggested the rush for resveratrol supplements may have been premature. A fierce and public debate has since emerged with camps of researchers publishing contradictory studies.
Scientists have had difficulty reproducing some of the original resveratrol findings. And studies in yeast, flies, and worms have questioned whether resveratrol really activates sirtuins and whether sirtuins are as instrumental to aging as first thought.
Meanwhile, in the human research realm, the drug maker GlaxoSmithKline terminated a clinical trial of a concentrated form of resveratrol that doctors had been testing on cancer patients because of unexpected side effects on people's kidneys. In the spring of 2012, it even came to light that a University of Connecticut researcher had allegedly falsified numerous studies suggesting that resveratrol has positive health effects.
But none of this means that nothing will ever come of sirtuins. Despite the controversy, a steady stream of studies continue to materialize and show that sirtuins play an important role in aging. A new study in the May issue of Cell Metabolism, for example, argues that there's a clear connection between resveratrol and sirtuins and suggests that sirtuins are key to slowing down the aging process.
Meanwhile, Sirtris Pharmaceuticals, the company that had been testing resveratrol for GlaxoSmithKline, has a number of newer, more potent and targeted sirtuin compounds in its pipeline that resemble resveratrol but are structurally distinct.
There's nothing particularly unusual about having a compound that works in the lab prove problematic in humans: In drug development, there are often false starts and dead ends. "People forget that we're not mice," Sierra says. "And what works in mice doesn't necessarily translate to humans as cleanly as we'd like."
Most researchers studying longevity believe that drugs to combat multiple age-related diseases will emerge eventually, just not for decades. In the meantime, Sierra does not advocate popping resveratrol or any of the other anti-aging pills already on the market. "We're still in an early stage of research," he says. "I don't have a tail. I don't have whiskers, and I won't take anything until we have good studies in humans showing a drug is safe and effective."
Until then, his anti-aging medication of choice is exercise.