In 1900, the average American could expect to live about 47 years; by 2010, that figure reached 78 years. But hand-in-hand with those massive gains in lifespan came a host of age-related, degenerative diseases that tarnish the golden years and cost the country billions of dollars in health care. And for every youthful, robust 80 year old on the tennis court, there’s a bedridden or wheelchair-bound counterpart who’s watching tennis on TV.

What causes cellular decline that leads to disease and, ultimately, death? And how can we slow the inexorable march of time and stay youthful for years to come? Anti-aging researcher Judith Campisi, Ph.D., a leading authority on senescent cells – older cells that have stopped dividing – has been asking these questions for more than twenty years. As a senior scientist at the Lawrence Berkeley National Laboratory and a professor at the Buck Institute for Age Research, Campisi is at the forefront of research on aging, cancer and cellular senescence. Campisi received her Ph.D. in biochemistry from Stony Brook University and completed postdoctoral training at the Harvard Medical School, then went on to become an assistant professor at the Boston University Medical School. Campisi has received numerous awards, including two MERIT awards from the US National Institute on Aging, and awards from the AlliedSignal Corporation, Gerontological Society of America, American Federation for Aging Research, and, most recently, the Longevity prize from the IPSEN Foundation.  Here, Ravi Dykema talks to Campisi about our modern passion for fitness clubs and antioxidants, in short, about our passion for retaining our vitality into old age. And you’ll be surprised at her advice.

RD: Over the years, we’ve gradually increased our lifespan – one expert with whom I spoke says by as much as 2 years per decade. Do you think kids born in the last 15 or 20 years will live to be 100 or older?

JC: Probably not; I don’t think significant increases in human longevity are going to be achieved in the near future. I’m not saying there won’t be further gains in average human longevity – there will be. But it’s not going to be at as rapid a rate as we’ve seen, especially in the last century. Most of the gains were due to better nutrition and antibiotics. What we’re dealing with now are chronic diseases of aging, like heart disease.

RD: The low-hanging fruit have already been captured?

JC: Exactly. And I think where we’ll see the most progress is in advances in the number of years of healthy life. Presently, in the developed world, long life does not necessarily mean a long quality life. A large segment of the population is going to spend somewhere between five to ten years with severe disabilities, disabilities that interfere with what’s called “activities of daily living.” That’s called morbidity, and it’s a huge economic burden as well as a huge human burden – not only for the person who’s old, but for the families who have to take care of them. I hope in coming years we’ll see what’s called a “compression of morbidity,” so people spend fewer years being disabled. That’s where the larger gains are going to be realized.

RD: People who are in their 80s and 90s grew up in a time when they didn’t know about free radicals, antioxidants, the benefits of exercise or the dangers of smoking and refined carbohydrates. My generation – I’m 60 – and younger generations do know. With our healthy lifestyles and our fitness club memberships, it seems we’d have a much better chance of staying healthy up until death, and of putting off death.

JC: Perhaps. But this idea that human lifespan has no limits if we just keep pushing the boundaries – so in a thousand years or so we’ll be living for 250 years – is unsupported by science. What is supported by science is that we can intervene in certain things that go wrong during aging. Drugs like the statins are lowering cholesterol, and probably having even broader effects, and I think we’ll continue to see more drugs like these in the future. And of course, healthy living is important. But, there’s always a random event, over which we have no control. You can have the healthiest lifestyle in the world, but if you get just the right types of mutations in the right genes in the right combination of cells, you’ll get a cancer. And there’s nothing we can do about that.

RD: You’ve been working with anti-cancer genes, DNA repair mechanisms that promote longevity, molecular pathways that protect cells against stress, as well as stem cells that relate to diseases. Are these areas of research pointing to healthy behaviors and lifestyles, things like exercise and diet that we’ve all heard about, or are we missing something? Is there some strategy that most people would be doing if they only knew?

JC: I don’t think so. I think people know what they need to do to maximize their chances of living older and healthier. You know: don’t smoke, don’t overeat, exercise, don’t inhale chloroform. There aren’t really any secrets to longevity; if there were, I’d be writing a book about them.

RD: I was asking the press person at the National Institute on Aging if I could interview the director, Richard Hodes. Before she even said “no,” she said “Look, he has nothing sexy to tell you, because all he’s going to say is you should do the things you’ve already heard about.” And then she listed them, things like what you just named, plus maintaining friendships and being treated promptly for diseases. Regarding that last item, getting treatment: some people I know avoid conventional doctors, preferring to rely on holistic health practitioners. Any thoughts?

JC: I’m not going to apologize for the values of modern Western medicine. I agree with many of the criticisms. But there is a large amount of medical knowledge about how to handle certain pathologies. If those illnesses are not checked, then I would predict future disability. For example, if you have bad joints, they’re going to get worse. And there are drugs that can help retard the rate at which they degrade. You might argue that those drugs have side effects. I would argue that there’s no such thing as a purely safe drug; all drugs have side effects. On the other hand, not treating that disease can do more harm than whatever the potential side effects are of some of these drugs.

I think it’s a mistake to ignore this very large body of evidence and experience in Western medicine in treating certain chronic diseases. Now, the main problem with Western medicine is there very rarely is a single physician who is looking at the patient as a whole. You have your joint problem, and your joint doctor gives you glucocorticoids, and then you have a heart problem, and your cardiologist gives you digitalis or whatever, and nobody is looking at the whole patient and saying “Do these drugs interact? Is this really the best strategy for this person with different chronic diseases?” That’s a huge problem. But it doesn’t mean that there aren’t very beneficial medications. Again, statins for lowering cholesterol have proven to reduce the risks of heart disease enormously.

RD: What about cancer?

JC: I don’t know what I’d do if I had a really bad cancer. The cures are horrible – there’s no question about that – but they do work. My sister had an ovarian cancer, and she went through four months of hell with the chemotherapy. But five years out, she’s alive and well and happy, which she probably wouldn’t be if she hadn’t done the Western medical treatments.

RD: Somewhat related to this is an issue that goes by the name “toxins.” There’s a popular theory that the world has become more and more “toxic,” and some people go to great lengths to avoid these toxins. Is the “more-toxins” theory true or not?

JC: It is true, especially for urban dwellers. There’s no question that air quality has degraded. And I would argue there’s no safe place; you go off to some remote mountain top in the Rocky Mountains, and chances are you’re going to be exposed to ionizing radiation from being so high. Or you go live in a cave, and you’re going to be exposed to radon, a carcinogen that’s in the ground. We’ve co-evolved with toxins. But it is an interesting question, and I think it really is not completely clear how much environmental exposure contributes to modern chronic disease.

RD: Can you speak specifically to cancer?

JC: Cancer is a great example; we know certain toxins in the environment, like radiation and asbestos, are cancer-causing. No question about that. But regardless of your environmental exposure, or frankly even your genetics, the single largest risk factor for developing cancer is your age. I work at the Buck Institute in Marin County (California), one of the wealthiest counties in the United States. It’s mostly white, middle- to upper-middle-class people, highly educated, and it has one of the highest rates of breast cancer in the country. So the good women of Marin are hysterical, of course. They really want to believe it’s something in the water or the air or the soil, and yet when you start adding up all the little things that contribute to breast cancer – having your first child after the age of 35, which most educated women do, having your first menstrual period earlier in life, which most well-nourished girls do, and other factors – that could pretty much account for that high rate of breast cancer. It’s not a very popular message.

RD: You said aging is the largest risk factor for developing cancer, and I know it’s true for a lot of other diseases. What is it about aging that produces this risk of getting a disease?

JC: That’s one of the main questions we’re asking. We’re looking at all these diseases that increase with age – neurodegeneration, macular degeneration, Type II diabetes, cancer – and asking, what do they have in common? Most of them are degenerative, meaning the tissue or the cell doesn’t work as well as it should. Cancer is the exception. A cancer cell is a cell that has had to acquire new functions; it does things other cells don’t. Cancer cells grow when they shouldn’t, they move around when they shouldn’t, they invade, they create a blood supply. I think of cancer as a gain-of-function disease. Other diseases of aging involve a loss of function.

Now, if you think about aging that way, it’s a little bit of a simpler problem. Is there a common biology that drives cancer and these other diseases? If there is, then that’s a basic aging process that might be driving all of these diseases. But maybe it’s not. Maybe it’s a coincidence. Maybe the degenerative diseases go up for one reason, and the cancers go up for a different reason. And they have nothing to do with each other. So we started out by looking at commonalities between cancer and the degenerative diseases of aging. One we found is the tumor suppressive mechanism. It’s ironic, but one of the mechanisms that keeps us from getting cancer when we’re young may be part of the process that’s driving age-related degeneration and, ironically, age-related cancer. And then, of course, down the road, we’d love to develop an intervention.

RD: What might a tumor suppressing intervention look like?

JC: A pill. Wouldn’t that be great? Here’s my fantasy. Every year, you take your annual pill, and it kills off all of your senescent cells – those are the cells that are aging – and you postpone a lot of age-related pathology, including late-life cancer.

RD: Would this be a low-priced pill, or the kind that only the very wealthy can afford?

JC: If it were up to me, it would be free. Actually, if the U.S. government were smart, it would be free, because it would postpone this period of morbidity. Talk about budgetary problems; this rising tide of medical costs is what’s going to bankrupt us.

RD: Is there really a possibility of such a pill?

JC: It’s certainly not mature at this point, but it’s not science fiction. There is now proof of principle, using a genetically modified mouse, that if you clear the body of senescent cells, you can postpone or even halt the progression of certain age-related, degenerative changes. It’s a start. We’re not going to genetically modify people, right? But once you have a genetic proof of principle, it then opens a path towards developing a pharmacological intervention, which is the only thing that will be practical in people.

Now, the big hurdle for developing any kind of intervention will be regulatory. Let’s say you’re an FDA inspector, and I say to you, “I have a pill that’s going to make people live longer, and live healthier. How do I set up a trial?” The FDA is going to say “No way.” FDA will not approve of the drug without a specific indication for treating a disease. So maybe we say “Okay, my longevity pill is going to prevent stroke,” and you do a prospective trial for stroke. But then you couldn’t claim that it would extend life span. The current U.S. regulatory climate would make it almost impossible to test a drug that would have overall health benefits without looking at a specific disease indication.

RD: Are there strategies that can engage a DNA repair mechanism that promotes longevity? Strategies that a person can do without a pill?

JC: We do not know of any genetic or pharmacological way to increase your DNA-repair capacity at will. But we do know DNA repair is maximized during sleep. That’s one of the reasons why people with chronic sleep problems often have health problems, and, in animal studies, don’t live as long.

RD: What about molecular pathways that protect cells? I’m wondering if you might say something like “Well, inflammation really is significant.” Or you might say, “You really can have an effect on how many free radicals are cruising through your body all the time by doing X, Y or Z.”

JC: Both of those things are correct. The tumor suppressor mechanism that probably links the degenerative diseases of aging and cancer turns on an inflammatory process, and inflammation is the one factor that links virtually every major age-related disease. Either inflammation causes the disease or it exacerbates the disease.

RD: Then how do we reduce inflammation?

JC: Well, there are steroidal drugs like glucocorticoids that reduce inflammation, but they have serious side effects, like leaching calcium out of bones and killing neurons when used over the long run. Then there are non-steroidal anti-inflammatories (NSAIDs), like ibuprofen or aspirin, both of which can cause stomach irritation and, if overused, liver damage. However, we are also finding that very low levels of NSAIDs seem to be beneficial; you’ve probably heard of taking baby aspirin to protect the heart.

One of the most remarkable findings is the effect of exercise on inflammation. When you exercise, your body makes molecules that reduce reactive oxygen species and inflammation. It doesn’t even have to be very robust; the American Heart Association says 30 minutes of exercise a day has enormous beneficial effects. Things like brisk walking, or dancing—anything that raises your heart rate above ambient levels and gets your muscles moving.

RD: What about serious athletes like marathon runners?

JC: They tend to have a lot of problems, especially joint problems. Some research shows that serious athletes have extremely short telomeres in their muscles, which may contribute to aging.

RD: Please explain what telomeres are.

JC: A telomere is a peculiar structure, a sequence that’s at the end of every single chromosome. That sequence binds certain proteins that allow the end of the chromosome to form a capped structure; it’s like the little plastic bits at the end of a shoelace, and the purpose is pretty much the same. It keeps the DNA at the ends of each chromosome from unraveling, and also tells the cell “This is the end of a chromosome. This is not a broken DNA. Don’t try to repair me.” We all have them at the end of every single chromosome. And if they fail, meaning if they shorten to the point where they can no longer function as a little cap, then the cell will try to repair that broken DNA, and that will often result in an error; that’s a mutation that can either kill the cell or start the cell on the path to cancer. As we age, the telomeres get shorter and shorter. There’s no evidence that at the end of your life, all of your telomeres are short; it’s not that simple. But the point is that they can shorten, and when they do shorten, that’s not a good thing.

Gillian Butler Browne, a French researcher, found that super athletes have extremely short telomeres in their muscles; in fact, by the time they’re in their 50s and 60s, they often have the muscle strength of a 70- or 80-year-old. Their muscles have just aged enormously. That shortening of telomeres is not found in people who maintain a healthy, moderate pace of exercise.

RD: Another theory for increasing longevity is calorie restriction. What do you think of that strategy?

JC: First of all, caloric restriction is very difficult to achieve without malnutrition. In laboratory animals, where caloric restriction was shown to extend life span, the animals were fed a balanced and nutritious diet. That’s hard to do in real life. It’s not something I would recommend anybody try on their own and personally, I can’t imagine why somebody would want to do it. Eating is one of the pleasures of life. And so far the research has been on animals. We do not know if it will work in humans.

RD: Here’s another issue: Stress. What do you think of the role of stress reduction in increasing life span?

JC: Chronic stress will definitely shorten your lifespan; that’s very clear. But be very careful about confusing stress and stimulation; there’s also very good evidence that both intellectual and sensory stimulation enhance longevity. In an experiment last year, two groups of genetically identical mice were put into two types of cages. One is the standard cage that has a water bottle and some bedding so the mice can sleep and cuddle up against each other, with lots of room to move around, but not much else. The other was called an enriched environment, with little running wheels and tunnels and all sorts of things the mice could play in. Both groups of mice were injected with cancer cells, and the mice in the enriched environment had significantly less cancer than the mice in the safe and comfortable but unstimulating environment.

So I think it’s very important to not confuse stress with stimulation, especially in terms of work. We may say our jobs are stressful, but are they really? Or are they just stimulating? It’s important to keep that distinction. I’ve considered my job to be high stress, but, in fact, if I think about it carefully, it’s really stimulation.

RD: As was, I hope, this interview. Thank you, Dr. Campisi, for helping us all age more gracefully.