Mitzi Perdue

Answer Lies in Preventing the Unraveling of Homeostatic Capacity

As the sponsor of the million-dollar Palo Alto Longevity Prize, Joon Yun, M.D., knows that with each passing week, a million additional people will die around the globe, and the majority of them will die because of aging-related diseases. Dr. Yun, who thinks about aging research as a race against time, is a medical doctor and president of Palo Alto Investors, an investment management firm with more than $1 billion invested in healthcare. From this perch, he has been able to delve into some of the most cutting-edge healthcare research that exists.

What he saw led him to wonder if aging wasn’t just an accumulation of diseases, but rather, a process. He wondered if instead of trying to treat individual diseases in a whack-a-mole type approach, could we instead look for upstream switches that could prevent or resolve aging?

For inspiration, he likes to think back to 1903 when the Wright Brothers achieved the first powered flight. Sixty years later, President Kennedy could realistically plan for taking people to the moon and back safely and eight years later, the mission was actually accomplished.

Likewise, since Watson and Crick discovered the code of life in 1953, scientific knowledge has also exploded. Thinking of this, Dr. Yun asks, “Why isn’t now the time to ask the scientific community to try for another moon shot? With all the biomedical research now available, why not hack the code of life and tackle hyper longevity?”

The questions was, how could he contribute? Calling on his undergraduate background in biology at Harvard, Dr. Yun decided to use the same model that evolution does. Evolution operates through the production of variation and from many possibilities, selects winners. He learned about the power of incentive prizes to nurture innovations and decided to apply it as a tool for aging research.

In Dr. Yun’s view, the current healthcare system, which treats the symptoms of aging, but not its underlying cause, helps individuals live longer. But there are two flaws with this approach. The first is, the longer individuals live, the more healthcare they consume, leading to feed-forward increases in costs. The second flaw is that aging remains a terminal disease.

Dr. Yun and the scientific advisors of the Palo Alto Longevity Prize are looking at aging from a more fundamental perspective. They realized that aging, if you go deep enough, is an unraveling of homeostatic capacity. A young man, who in his 20s had both healthy blood pressure and healthy blood sugar, may find that in his 50s, his eroding homeostatic capacity no longer effectively regulates these functions and now has hypertension and diabetes.

Therefore, Dr. Yun and his team elected to focus on improving homeostatic capacity as a way to improve health, and improving health as a way to improve longevity.

A Proxy for Homeostatic Capacity

If improved homeostatic capacity is the goal, is there a proxy for evaluating it from a prize perspective? Dr. Yun’s prize team chose heart rate variability, or HRV, as a biomarker for homeostatic capacity. “HRV is a measure of beat-to-beat variability of the heart rate,” he explains. “HRV is a surrogate for cardiac autonomic capacity, which itself is a component overall homeostatic capacity. Emerging empirical evidence suggests a correlation of declining HRV with chronologic age and the presence of aging-associated diseases, making it a potentially useful surrogate marker.”

There have been numerous studies validating HRV as a biomarker for homeostatic capacity. Interventions such as exercise, sleep, and caloric restriction that help mitigate diseases of aging have been shown to increase HRV. Meanwhile, smoking and chronic stress, which both have been implicated in the increased risk of aging-related diseases, are associated with lower HRV.

Dr. Yun also likes HRV as a biomarker for the prize because data can be acquired relatively inexpensively and noninvasively from a wide variety of devices. HRV data is different than most conventional diagnostic biodata collected from blood samples or tissues because HRV can be gathered continuously. ‘Most biodata today lack temporal resolution,” he points out. “Most data we get from the body are usually collected at a certain point in time, and yet we know the body is a dynamic system that changes continuously with variations throughout the day and in different contexts. HRV is one of the few measures of function that generate continuous, real-time data that can help assess system dynamism, which is a key feature in understanding homeostatic capacity.”

He is excited about the possibilities that the prize is unleashing. There are more than 20 teams from throughout the world that as of now have signed up to compete for the prize, and he’s enthusiastic about what he’s seen so far. “It feels inevitable that we’re going to solve aging,” he predicts.” All we’re doing is pulling up the timeline.”

Palo Alto Longevity Prize

The Palo Alto Longevity Prize is a $1 million life science competition dedicated to ending aging. The aim is to nurture innovations that end aging by restoring the body’s homeostatic capacity and promoting the extension of a sustained and healthy lifespan.

There are two prizes available and teams may compete for one or both prizes. A $500,000 Longevity Demonstration Prize will be awarded to the first team that can extend the mean lifespan of its wild-type mammalian intervention cohort by 50%. The second registration deadline for this prize is July 15, 2015.

A $500,000 Homeostatic Capacity Prize will be awarded to the first team to demonstrate an intervention that can restore homeostatic capacity (using heart rate variability as the surrogate measure) of its aged wild-type mammalian cohort. The second registration deadline for this prize is also July 15, 2015.

Over 20 teams from all over the world including teams from Stanford, UC Berkeley, GW, UNC, Albert Einstein College of Medicine, U Nebraska, U of Iowa, Texas Heart Institute, Charite University School of Medicine, Berlin, Germany have already signed up proposing a wide range of approaches to win the Palo Alto Longevity Prize including using stem cells, gene modification, hypothalamic regulation, neuromodulation, pituitary hormones, inflammatory pathways, regenerative medicine, and a variety of other approaches that are not yet public.

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