Forever Youngish: Pitt's Aging Institute Translates Research to the Clinic

Johanna Quaas is a gymnast. In recent videos, she does somersaults, headstands and lithe leaps and turns. With arms bearing her entire weight on the parallel bars, she holds her body horizontally or upside-down, pausing for long, graceful moments before lowering herself again. It’s more than impressive — it’s astounding. Quaas was born in 1925. 

Though she’s in her 90s, Quaas would put most young people to shame with her athleticism. Biological pathways we’re just beginning to understand give some people extraordinary resilience to aging, while leading others to become worn down in their 50s. Researchers at the University of Pittsburgh Aging Institute are working to unlock the genetic and metabolic secrets inside people like Quaas — and duplicate them with practical therapies. 

This September, the institute welcomed new director Toren Finkel, who will lead a basic and translational research effort on aging that is unprecedented here.

“Aging is the biggest risk factor for every [chronic] disease that we have to deal with, but it’s always been dismissed as nonmodifiable,” says Finkel, who comes to Pitt from the National Heart, Lung, and Blood Institute and was named the inaugural holder of the G. Nicholas Beckwith III and Dorothy B. Beckwith Chair in Translational Medicine at Pitt.

“It’s becoming possible to think about intervening in the rate of aging, pharmacologically. You could really slow the rate that you age, and thereby, slow the rate that you develop all of these diseases. That’s incredibly exciting,” Finkel adds. 

As we age, a lot of things tend to go wrong in our bodies. Our cells’ housekeepers fail to show up. Our energy sensors sense wrong. Our nondividing cells cause trouble. The telomeres — caps on the ends of DNA — wear down. Genes get switched on and off at the wrong times. The bacterial population in the body can veer away from a healthy mix. 

What scientists are beginning to realize is that these processes are often connected, that they can show up as many different diseases that have a lot in common, and that certain points along these pathways offer promising drug targets. In other words, the common chronic diseases of aging — including neurodegeneration, cancer and heart disease — are linked.

Pitt and UPMC officials believe a holistic research effort that unites researchers from a variety of fields under a leader who’s willing to totally rethink aging could yield enormous benefits.

More than 90 percent of elderly people today have at least one chronic health problem, and three-quarters have at least two. Such diseases consume three-quarters of U.S. health care dollars.

“Toren Finkel is a fantastic researcher and wonderful human being who’s going to fit into our culture extremely well,” says Steven Shapiro, the executive vice president and chief medical and scientific officer of UPMC. “He has not only a great understanding of basic science, but an urgency to translate this into clinical programs and help patients. He spent the first half of his career defining these pathways. Now he wants to do something to help people.”

With the renowned Charles Reynolds, UPMC Endowed Professor of Geriatric Psychiatry, at the helm for many years, the institute already offers top-notch clinical care for Western Pennsylvania elders and caregivers. It educates professionals and laypeople in geriatrics. And it has conducted important clinical research while building its basic science portfolio. 

Finkel will expand the institute’s investigations in geroscience, the study of the relationship between aging and disease. That’s not to be confused with gerontology, the study of aging, or with geriatrics, the branch of medicine dealing with treating disease in elders. 

Geroscience aims to discover, test and develop drugs and lifestyle changes that could lengthen not only life span, but also health span — the period of life during which a person remains free from serious illness. 

An interesting thing about people who survive nearly a century or longer is that they tend to remain in good health for most of their lives. Life span and health span are, somehow, tightly linked.

Finding drugs that alter aging pathways enough to lengthen health span could fundamentally alter the practice of Western medicine, which now emphasizes the diagnosis and treatment of disease. 

“Your DNA is repaired. Your mitochondria are strong. You avoid developing that cancer in the first place, you avoid developing that lung fibrosis, you avoid developing that coronary disease,” says Mark Gladwin, who holds the Jack D. Myers Chair of Medicine and helped recruit Finkel to Pitt.

“We’re not trying to make people live beyond 120,” he adds. “But wouldn’t it be great if you could live a strong, healthy life until you’re 95 to 120 and die peacefully in your sleep? Wouldn’t that be the dream we’d all have?” No one dies purely of “old age,” but a sudden deadly stroke or fall might be an enviable exit. 

In the United States today, there are 46 million people age 65 or older, a number expected to double to 98 million by 2060 — nearly a quarter of the country’s population. By 2030, about 2.3 million older U.S. residents will require skilled nursing care, a 75 percent increase from 2010. This isn’t just happening in this country. Sometime before 2020, the number of people on the planet age 65 and older will surpass the number of children under age 5, a first in human history. 

Caring for these folks can be difficult. More than 90 percent of elderly people today have at least one chronic health problem, and three-quarters have at least two. Such diseases consume three-quarters of U.S. health care dollars. A 2013 study published in Health Affairs concluded that delaying aging’s complications by just 2.2 years would lead to a savings of $7.1 trillion throughout 50 years. 

Industry has caught on to the promise of anti-aging drugs. A small study by the drug company Novartis made headlines in late 2014 when it found that giving a drug called rapamycin to elderly people boosted their response to the flu vaccine. (We’ll come back to rapamycin in a bit.) Google’s life-sciences company Calico partnered in 2014 with pharma giant AbbVie to run clinical trials on anti-aging compounds. 

“[Geroscience] really started to gain traction in the last five years. There’s a lot of interest in trying to look at common themes across the system so that we can be able to treat aging more systemically and less from a disease-specific approach,” says Fabrisia Ambrosio, an associate professor of physical medicine and rehabilitation who has helped nurture basic aging research at the Aging Institute for the past several years. “Why is it that over time our cells seem to default toward this more dysfunctional nature? And what can we do to counteract it?” 

Finkel and his colleagues are determined to find out. The chief strategy: to identify and test small molecules in house, then pass them along to the institute’s translational and clinical scientists for human trials and eventual commercialization. 

Keep reading about Toren Finkel and research being conducted about the biology of aging at Pitt.