How can some of the world's oldest people also lead unhealthy lives?

­There have been cases in which the world's oldest people -- and we're talking way over 100 years old -- have also lived thoroughly unhealt­hy lives. Centenarians (people who are 100 years of age or older) like Madame Jeanne Calment, who smoked until she was 100 and died in 1997 at age 122, aren't supposed to live as long and certainly not in good health, as Calment did. They're supposed to live like fitness guru Jack LaLanne, who himself is holding steady at age 94, and is healthy enough to play Hercules in the 2006 TV movie "The Year Without a Santa Claus" at age 92.

LaLanne's longevity is self-explanatory; he drinks fresh juice each day and worships at the temple of fitness. But a 100-year-old who smokes and is still alive -- healthy and happy, even -- defies science. Why aren't people like Calment riddled with cancer or felled by heart disease? Why aren't they hooked up to all manner of life-support devices and kept alive by the sheer will of their physicians?

Those questions led some scientists to investigate these inexplicably long lives. The race toward discovering the key to this type of longevity still continues. However, scientists have figured out that somewhere within our genetic makeup, some of us appear to have a mutation -- a leg up, really -- that staves off cellular death. It's also possible that if researchers can identify the gene or genes responsible for long life, the rest of us can benefit through gene therapy.

Enough with the questions; let's get to some science, shall we?

As far as HowStuffWorks.com can tell, no one's ever put a centenarian on a near-starvation diet. That kind of research has been performed instead on worms, yeast and rats. That last example has yielded some particularly important findings, as what we see in rats (as fellow mammals) often translates to humans as well. Lab tests on rats found that those that eat 40 percent fewer calories than their counterparts -- called caloric restriction in the field of longevity research -- tend to live longer, healthier lives. The same goes for worms and yeast. Why would this be?

­It turns out that for such an elegant system, the human body can be fairly rough on itself. Our bodies crave certain foods but doesn't appear to take into account how the process of eating affects our cells -- specifically, how insulin can damage them. Say, for example, a person develops an insatiable desire for the chocolate bar that he or she craves, blood sugar levels spike, spurring insulin production. Normally, this is a good thing because insulin governs glucose concentration in blood. However, it can also damage or even kill cells. Cellular death is what causes death by old age; as we age, cells stop multiplying and when enough do, our bodies simply can't function properly anymore.

While insulin has been shown to have devastating effects on cellular health, it's just one of many potentially harmful hormones that our bodies use to carry out cellular processes. Adrenaline's another good example; we use it to spur the fight-or-flight response that allows us to escape or ward off danger, but it can also create cardiac bands -- blown-out strips of cells -- on heart tissue.

The body may be overly harsh on itself when carrying out these processes, but it's also aces at protecting itself from external conditions. This is where the starvation diet comes in. One hypothesis states that a calorie-restricted diet causes the body to enter survival mode. In this state, the body's survival mechanisms -- and one gene in particular -- kick in. In fact, two wholly independent studies (one out of Harvard, one from Massachusetts Institute of Technology -- published within 16 days of each other in June 2004) found that the SIRT1 gene begins to both combat cellular destruction and cause the body to burn fat to make up for the carbohydrates and proteins that the body doesn't receive through diet. This combination of shedding fat and protecting cells creates a perfect storm of longevity, according to the Harvard and MIT researchers.

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­The hypotheses from the Harvard and MIT studies aren't the only theories floating around the aging research field that attempt to explain this type of longevity. Nor is SIRT1 the only candidate for what will surely be called the Ponce de Leon gene. In fact, studies have concluded that other genes may be responsible for preternatural longevity among humans. This is not to say that geneticists and biologists have abandoned the decades-old findings concerning calorie-restricted diets. Quite the contrary -- they accept as fact that near-starvation leads to longevity. However, it remains a mystery exactly how cellular processes and the genes responsible for regulating them manage to continue despite this starvation.

In 2007, the gene FOXO3A was shown to have a proven effect on worms' life spans. Researchers turned the gene on and off by adding compounds to some of the worms' food that targeted and shut down other specific genes in their bodies. When the gene was switched on, the worms lived longer. By 2009, FOXO3A had begun to establish itself as the de facto gene for creating longevity in humans after studies emerged that showed elderly Japanese people (Japan has the highest per capita ration of centenarians of any nation) shared active FOXO3A genes [source: Okinawa Centenarian Study]. Active FOXO3A genes have also been found in elderly Germans, suggesting that the gene is not racially specific in humans.

Still another group of researchers believe that the key to longevity lies in the gene responsible for regulating insulin production. After studying a population of centenarian Ashkenazi Jews, researchers at the Albert Einstein College of Medicine in New York concluded in 2008 that a mutation on the insulin-like growth factor (IGF-1) gene is responsible for very long life in humans. The group found that women in the population who were centenarians or the children of centenarians were more likely to feature this genetic mutation, which impedes the production of insulin. This could explain a lack of cancer in centenarians, since insulin is related to growth hormones, which can aid in the development of cancerous cells.

Some biologists pooh-poohed the Einstein College study's findings; if genetics plays a role in longevity, then life-extending genes should appear in both men and women. There is, however, an argument that supports women being blessed with longevity genes over men. Specifically, women play a more important role in genes' main concern -- reproduction.

­There is a school of thought, posited by biologist Richard Dawkins, that every organism that can reproduce is merely a vessel for the transference of its genes. It makes sense: While humans live and die, our genetic lines can live on indefinitely through reproduction. In essence, the individual has a mutually beneficial relationship with his genes.

Under Dawkins' theory, then, genes couldn't care less if we can live forever, since we need only reproduce to fulfill our genetic destiny. This is the predominant view of evolutionists and geneticists, although it has been amended somewhat over the years. Obstetrician/gynecologist Ruth Fetts pointed out that since women play such a vital role in human reproduction and child rearing, a gene that extended their healthy lives should also extend the length of time a woman can reproduce, hence improving the chances of producing and raising more offspring.

Clearly, there are several competing theories and genes that explain genetic longevity. It's interesting that none seem to contradict the others. More likely than a single gene, there are probably a number of genes working in conjunction to maintain longevity. It would be a difficult job to keep a human healthy through genetics alone. In addition to disease and environmental factors -- like cigarette smoke, a poor diet, alcohol or other bad habits -- cells would have to be protected from the Hayflick limit. This is the maximum number of times a cell can divide in its lifetime. Biologist Dr. Leonard Hayflick noticed that cells divided 50 times before stopping. As the cells approached 50 divisions, they divided less rapidly. Being a curious fellow, Dr. Hayflick tinkered with cells, removing the nuclei of old cells and replacing them with young ones. He found the cells divided again with renewed vigor, slowing again as they reached 50 divisions before stopping.

This finding led Hayflick to conclude that cells have a set life span governed by our DNA. Logically, then, any gene that extends cellular life should also extend the life span of the animal the cells comprise.

­There's a lot of anecdotal and clinical evidence that geneticists and biologists are sifting through to get to the foundation of unnatural longevity. How much of a factor does maintaining a healthy lifestyle play in keeping people healthy and alive long after their peers have bit the dust? Is the Jack LaLanne method the correct one? Tom Parr, who may have been the oldest person to ever live, would support this notion. Parr is believed to have been born in 1483, at a time when the average life expectancy in his country was 32 years [source: Grassby]. He lived on a simple diet of green cheese, onions, bread and buttermilk. He didn't smoke and rarely drank. He lived as a bachelor until age 80, when he took a wife and began having children. At age 100, he was publicly chastised for fathering an illegitimate child with another woman.

By the time Parr was 152 years old, he made a trip to London to visit King Charles of England. He was treated to a two-week-long party, indulging in alcohol and all manner of food, whereupon he died. An autopsy revealed nothing -- he hadn't suffered from any visible disease or ravages of age. It seems Parr died from suddenly abandoning his strict adherence to the healthy living he'd practiced his entire life.

While Parr and LaLanne's longevity support the notion that healthy living extends healthy life, science still has the matter of people like Madame Calment to deal with, who, you'll remember, smoked until she was 100.

There's ample support for the belief that the key to longevity is found in the genes. Dr. Thomas Perls, who directs the New England Centenarian Study, points out that a fair number of centenarians have siblings or immediate family members of nearly equal age [source: Perls]. Without a genetic explanation, the statistical probability of a nuclear family with three or even more members who live past 100 is too unlikely to support any other conclusion.

Again, it seems like researchers are hot on the trail of isolating the genes responsible for producing longevity. That discovery could mean an extension of human life expectancy along the order of the decades added by the discovery of antiseptics and the advent of hospitals. In the meantime, it's probably a good idea to take a cue from Jack LaLanne rather than Mme. Calment, just to be on the safe side.