Time, longevity, and human aging
In front of a mixed university audience—aging baby boomers and invincible twenty-somethings—at the 2004 Penn State Lectures on the Frontiers of Science, Robert Mitchell, professor of biology at Penn State, tackled that nagging question: Why get old anyway? What follows is a conversation Research/Penn State had with Mitchell after his talk.
R/PS: How long can humans live?
RM: We have to distinguish between maximum lifespan, which is as long as any human has ever lived, and life expectancy, which is how long you could live predictably, based on insurance statistics, for example. As far as maximum lifespan goes, we suspect it's around 125 years. There's no evidence that humans can live any longer than that. But as far as life expectancy goes, decade by decade we see that going up and up and up. We're at the point where it's somewhere around 76, 77 years. And that will continue to rise.
Most geneticists will tell us that about 30 percent of our longevity depends on our genetic make-up. That surprises a lot of people. That's saying that 70 percent depends on environment, behavior, what you eat, how careful a driver you are, if you smoke, if you wear your seatbelt. These things have a profound impact.
I don't suspect that we'll see maximum lifespan increasing beyond 125, unless we start juggling people's genetic codes, and I don't think anybody's ready to do that.
Jennifer Howell © 2004
A baby born today has a life expectancy of about 76 years.
R/PS: Who is the oldest recorded living person?
RM: Jeanne-Louise Calment of France, who died in 1997, lived to be 122 years and five months. This woman was quite a character, if you read about her. She was bright and spry into her later years. She took up fencing at age 87. I hesitate to say this, but she smoked until she was 117. The only reason she quit is because she got tired of asking people to light her cigarettes for her. She couldn't see well enough to do it herself.
R/PS: Why is 125 the magic number?
RM: It's evolved. The program, so to speak, within our system has evolved to the point that we just can't get beyond that. It's a matter of repair. We only have so many repair systems that have evolved over millions of years. The best an individual can do is keep repairing damage, up to a certain point, and then you just can't do it anymore. Long-lived animals have much better repair systems then short-lived animals. That's genetic and it's evolved that way.
R/PS: So what about other animals? How long do they live?
RM: Longevity correlates with a number of other factors, like body size, duration of growth period, fecundity (rate of reproduction), and rate of energy metabolism. In general, larger animals live longer. The smallest and shortest-lived of the mammals, and also the one with the fastest metabolism, is the shrew. We all know that if you want to know how old your dog is you take your dog's age and multiply it by seven and that gives you human years for your dog. What's really going on is that a dog has a metabolic rate that's about seven times faster than a human's metabolic rate.
R/PS: How did you get started in this research?
RM: I first got interested in aging by accepting a fellowship with the National Institutes of Health, which was trying to encourage young Ph.D. graduates to do research in that area. Prior to that, I hadn't thought much about aging. I don't think very many 26-year-olds do.
At that time, in the late 1960s and early 1970s, there was little mention of aging in any biology textbooks. Our library at Penn State had just a few journals specific to aging. Today there are dozens. And quite frankly, there was very little good biological research about aging. That began to change in 1974 when the NIH formed the National Institute for Aging.
R/PS: Why the increased interest?
M: In 1900, only three million people in America were over 65. Today, 37 million people are over 65. That's 12 and a half percent of the population. In the next 30 years, 70 million people will be over the age of 65. That's 22 and a half percent. There's no question that people are living longer and that people are generally healthier in their late lives. Also, the number of people in this country living past 100 has increased. Today there are 50,000 people over the age of 100 in America. By 2050, 800,000 people will be over the age of 100. There are lots and lots of people living longer and longer and that's interesting from a biological, economic, and sociological point of view.
R/PS: Can our economy and our health care system handle so many people who are going to be living for so long?
RM: It's an issue, not so much for the biologists, but for the sociologists and the health policy people. To have so many people living for so long is costly. It used to be that people could expect to live 12 years after retirement, but now they can expect to live 25 more years, without a regular salary. I think younger people are worried that they're going to have to work longer to support the older people who are living longer.
Courtesy Robert Mitchell
Robert Mitchell
R/PS: What are some of the most exciting discoveries you've seen in the field of aging in the past 30 years?
RM: Two things. The first: It was always thought that once you took human cells out of the body and grew them in a dish they would divide and divide and divide and not age. In the sixties, we learned that there is a limit to how many times a cell could divide in a dish. They do age and have a limited lifespan. We know now there is some kind of a clock that limits the longevity of these cells. That discovery in the sixties led hundreds of investigators to start working with human cells in culture—we say in vitro—to see what it was that was limiting their life span. That's called the Hayflick limit, the limited number of times a cell is able to divide. So, that discovery probably did more than anything else to spark all kinds of research, cell and molecular biology research, on the basic mechanisms of aging.
The second thing, in the nineties, has been the discovery of specific genes in simple animals—fruitflies and roundworms that we use to study the aging process—that have profound effects on rate of aging and natural lifespan of those organisms. Many people believe that even though the code within our cells is made up of thousands of genes, it might only be several dozen that are really key genes as far as programming our rate of aging and longevity. A lot of people right now are looking for those genes. And it's one thing to find a gene, but it's another to figure out what it does. What does the protein it makes do? That's the next hurdle. For example, in one experiment, if you insert a gene which codes for an enzyme that neutralizes dangerous free radicals in a fly or a roundworm, then those animals live longer. That enzyme is called SOD, for superoxide dismutase. Free radicals cause havoc in cells and accelerate the process of aging.
And we've only had the ability in the last 10 years to do these kinds of genetic manipulations—identify genes, knock out genes, insert genes—and that's opened a whole line of investigations.
