Clinical trials are underway at the University of Pittsburgh Medical Center’s Aging Institute to find the formula for the fountain of youth. Researchers at the lab are dedicated to unlocking the mysteries of aging — and possibly inventing a pill to stop what so many dread.
Aging Institute director Dr. Toren Finkel says his team is developing new anti-aging strategies, including medications that directly target the aging process, as well as investigating current medications that may extend lifespan and health span — living longer healthier.
“We have 14 labs where researchers are trying to understand different angles on how and why we age, studying different systems in everything as simple as a worm or fly to more complex things closer to us like mice,” Finkel explains. “As a group we think we can derive core principles and pathways modifiable by small molecules or drugs to try to create new meds that expand our lives while keeping us healthy and that have a propensity to slow chronic disease.”
Finkel is most excited at beginning a small trial with 50 people over the age of 70 looking at combatting and preventing what he calls “inflammaging” — aging caused by inflammation. His hope is to first develop a blood test that would indicate who will age well and who will age poorly.
“We’re looking at Interleukin 6 (IL-6), which has been found to be a marker of inflammation, which is a big driver of aging, and whether high levels of IL-6 can cause frailty as we age — such as not being able to get out of a chair or walk across a room well.” The big question, Finkel says, is whether inflammation is a cause or correlation, which he says is an important distinction.
“We’re looking at whether inflammation and inappropriate immune response accompanies the condition of frailty or whether it’s a cause of the condition. There are indications that inflammation might be causatively linked,” which opens up the avenue of developing new pathways and medications to combat frailty as we age, so we can live a healthier and more active life for longer.
“Around 10 to 20 percent of lifespan has to do with the genetic cards we’re dealt. The rest is up to us.”
“We’re selecting patients for the trial who are what we call ‘pre-frail.’ They’re able to get out of their chair and get around, but it’s starting to get harder. We’ll be giving them low-levels of anti-IL-6 antibody, enough to ratchet down their IL-6 levels, and will follow them for a year against a placebo group. Our hope,” Finkel says, “is that we not only are able to slow the rate of frailty progression but ultimately make them feel better, less fatigued, and have clearer thinking.”
You may well be asking how genetics play into the healthy aging equation, and whether a genetic predisposition plays a big part in defining how long we’ll live a healthy life.
“People have looked to see if there are longevity genes, and there are some that have been implicated,” Finkel says. “When it comes to how much our lifespan is determined by what our parents give us and what we do, around 10 to 20 percent of lifespan has to do with the genetic cards we’re dealt. The rest is up to us.”
“In general,” Finkel says, “a genetic signature for a long life is really only about the people who live into their 90s and beyond without chronic diseases, and who have the absence of ‘bad’ genes. It’s not,” he says, “that they have something the rest of us don’t. Rather, they’ve avoided inheriting the thing that contributes to having, say, a bad lipid profile. The absence of bad things does allow you to live a longer lifespan. But most people want to have a longer quality of life, not just duration of life.”
Finkel says the jury is still out, but the Aging Institute researchers do think that manipulating pathways related to aging will slow the propensity of people getting diseases. He gives an example learned from mice that die from the same things as humans. “If you give a mouse everything it wants to eat, it will die from a certain range of diseases. From doing an autopsy on the mice, about 5 percent have no diseases and so died of old age. If we limit their calorie intake, they live longer, and now 30 percent or so die without evidence of disease.
“If translatable to humans, here’s an intervention that increases lifespan but changes propensity of diseases. too. So you have a longer, disease-free, and happier life, although you might be a bit hangry.”
“It’s a leap of faith, but I’m going to say we should see [anti-aging] meds in the next 10 years.”
If 90 is destined to be the new 50, it’s likely that most of us would be on board with an anti-aging pill. “Death isn’t inescapable, of course,” Finkel says, “but those who eat right and exercise do live longer. What we’re exploring is whether there are ways to use medications for the population where eating and exercising right is difficult.”
It’s hard to find naysayers when it comes to the notion of living a healthier longer life, but Finkel says there are people who are incredulous at the notion that there could one day be a pill for aging.
“Our goal is to demonstrate replicating in humans the positive results we’ve proven in other organisms. It’s complex. Even at the same biological age, every organ in our body ages at a different rate. My feeling is that when I grew up and was in medical school, I was taught aging is a process that can’t be regulated. But with regulation comes the ability to intervene — it’s what we’re researching at the Aging Institute and trying to be smart about. If you look at President Franklin D. Roosevelt 50 years ago, there was hypertension then as there is now, and Roosevelt died of a stroke. Today there are lots of medicines that can control that.”
Asked to make a casino bet on when we might see an anti-aging pill, Finkel is thoughtful with his answer. “First,” he says, “new medications will be directed to specific chronic diseases, and once shown effective in disease states in the elderly, we can back up and look at if taken preventively, would it help with overall aging. It’s a leap of faith, but I’m going to say we should see [anti-aging] meds in the next 10 years.
“It’s an incredible time that began 20 years ago looking at lifespan genes in worms. Those observations have changed the fundamental basis of how we think about our own longevity. It’s a wonderful example of how basic science opens opportunities of research, and how a simple organism like a worm can ultimately impact human health.”