The most meaningful way to look at longevity is not just the number of years, but the number of healthy years
When we think about old age, most of us associate that with becoming debilitated. But what if we could age with the same health we had when we were young? “I have a favorite way of thinking about longevity, which is healthy longevity,” says Dr. Eric Verdin. This is your “healthspan” — your healthy years of life. “We all want to live longer, but we want to live longer under really well-defined conditions — that is, optimal health and functional status equivalent to our better years,” says Dr. Verdin.
“We all want to live longer, but we want to live longer under really well-defined conditions — that is, optimal health and functional status equivalent to our better years,” says Dr. Verdin.
Aging was once a fixed risk factor for disease — that’s changing
At the Buck Institute, they pursue the question: What is aging? In their work, the scientists there have identified nearly 700 genes that control the aging process. One of the key things that they’ve learned is that aging is meallabe. Using drugs, they can dial up or down certain genes to change life expectancy.
Another key discovery is the link between aging and the development of disease. The idea that when you get old, you get sick is not new — “what was not clear is why,” explains Dr. Verdin. Their findings show that the pathways that regulate aging also regulate the development of many chronic diseases. “Therein lies the incredible potential of this field of research,” says Dr. Verdin. Counter to the way that medicine currently targets specific diseases, we someday may be able to target these diseases as an entire group by targeting the aging process as a whole.
“When I went to medical school, which was a long time ago, the unmodifiable risk factors had two categories, which were age and gender,” says Dr. Verdin. “What I’m telling you today is that age is becoming a modifiable risk factor. It is something that we can tune.”
“What I’m telling you today is that age is becoming a modifiable risk factor. It is something that we can tune.”
Understanding biological age could change how we practice medicine
“Each of us has two ages,” says Dr. Verdin. Your chronological age is the number of years you have lived. And your biological age is a reflection of how you are aging — for example, are you 65 but look more like a 50-year-old? Dr. Verdin offers the example of attending his high school reunion at 60. Some of his former classmates were aging well, some not as well, and some had already passed away.
A number of new aging clocks are in development to help us determine biological age. Some of them even determine how long you can expect to live if you continue to live in the same way. It’s “very early,” says Dr. Verdin, but “our vision is that they could really become part of medical management, not when you’re 65 years old, but hopefully when you’re 40 or even earlier.” (The aging process begins at 30, he notes.) At the moment, it’s not possible to deploy this technology at a clinical level, but we can imagine a future where you can tell a 35-year-old that they’re on their way to living to 70 and help them modify their aging based on these results. “Right now, medicine is incredibly good at treating people,” says Dr. Verdin. “I think [these clocks are] going to change the way we practice medicine in the future.”
Environmental and lifestyle factors are the biggest determinants of longevity
A new study from Calico shows that unless you have a first degree relative who is a centenarian, only seven percent of your longevity is determined by genes that you’ve inherited from your parents. The rest of the 93 percent are environmental factors — what you eat, how much you sleep, your stress levels, your social relationships. (If you do have a centenarian relative, there is a strong genetic link to your longevity, and in most cases you can expect to live to or beyond 90.)
“Everyone knows that you should exercise, not eat too much, and not be stressed,” says Dr. Verdin. “But we see incredible discrepancy between people in terms of their ability to implement these [practices] into their daily lives.” Part of the Buck Institute’s research is looking at why the molecular mechanisms of these interventions is linked with aging pathways. With the sedentary lifestyle of food abundance in our society, many people are not aging well. The likelihood that those who reach 65 are carrying a chronic disease of aging — heart attack, stroke, Type 2 diabetes, many forms of cancer, macular degeneration, hearing loss, sarcopenia, osteoarthritis — is 80 percent. By the age of 70, 70 percent of people carry two of these conditions. “So even though we live long, I don’t think we live well in our old years,” says Dr. Verdin. His goal is to find a way to eliminate these afflictions of old age.
“My prediction is that if we were to find a way to optimize everyone, most people could expect to live to 90, 95 in good health,” he says.
One way to target the aging process is by tackling certain chronic diseases of aging
How does aging occur in the body? The term senescence refers to “a program that is built in every one of your cells that allows it to detect whether the cell is being stressed in a way that is possibly leading to a cancer or to irreparable damage,” explains Dr. Verdin. If one of your cells has a mutation that forces it to start uncontrollably dividing, the senescence program sends an SOS to the immune system to slow down the cell and prevent it from continuing to divide.
From the age of 20, the process of senescence occurs to successfully eliminate potentially harmful cells. But through the work of Verdin’s Buck Institute colleague Judy Campisi, we’ve learned that, as the immune system ages, it isn’t able to remove these cells as effectively. Plus, these mutations and defects become more frequent. “The net result of these two things happening together is that the number of senescent cells in your tissues progressively increases as you age. And as these cells are secreting inflammatory markers, the thinking is that they are responsible for what people have called ‘inflamm-aging,’ this chronic inflammation associated with aging,” says Dr. Verdin. The question that emerged from this research is: Can we get rid of these cells?
Campisi and her team have proved that they can target senescent cells in mice, causing these mice to live longer and protecting them against a number of chronic diseases of aging. This discovery has led to clinical trials on a number of conditions where there is increased senescence. One of these conditions is macular degeneration. This is a great example of how the field is working with current routes for FDA approval: targeting unique diseases for drug approval. “The hope would be that if this molecule works in the eye, that it’s going to work also in the lung, in the knee, and so on,” says Dr. Verdin
Another approach for FDA approval is to target aging as a whole. Nir Barzilai at the Albert Einstein College of Medicine is testing the anti-Type 2 diabetes drug metformin in normal subjects. These subjects are not diabetic and will be scored for the development of chronic diseases, including new onset of heart attack, stroke, dementia, and cancer. If this five-year trial, called TAME (Targeting Aging with Metformin) is effective against preventing this kind of morbidity, “the key question would be, who do we give [metformin] to and when?” asks Dr. Verdin. There are no drugs that come without side effects, but “I can envisage a future where… if you are at risk of heart disease or of another chronic disease of aging at age 50, your doctor might actually prescribe metformin as a preventative medicine.”
“I can envisage a future where… if you are at risk of heart disease or of another chronic disease of aging at age 50, your doctor might actually prescribe metformin as a preventative medicine.”
Human age does have its limits, but we have reason to be optimistic for a healthier future
Given the data we have about the oldest people in the 100 billion of us that have lived, “the maximum lifespan of humans is likely to lie around 115.” Those who claim that immortality — or even a life of 150 years — is possible have “been a problem for us,” says Dr. Verdin. “It detracts from the amazing work that we can do. Imagine a world where everybody would live to 95 in great health. The societal impact of such a discovery would be earth-shattering.”
Imagine a world where everybody would live to 95 in great health. The societal impact of such a discovery would be earth-shattering.”
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