$500,000 Palo Alto Homeostatic Capacity Prize
The $500,000 Palo Alto Homeostatic Capacity Prize will be awarded to the first team to demonstrate that it can restore homeostatic capacity (using heart rate variability as the surrogate measure) of an aging reference mammal to that of a young adult.
To be announced soon!
WHAT IS HOMEOSTATIC CAPACITY?
Homeostatic capacity is the capability of systems to self-stabilize in response to stressors. A simple way to visualize homeostatic capacity is to imagine a WeebleTM, the popular self-centering children’s toy. For organisms, it is life’s foundational trait—itself comprised of a hierarchy and network of traits—endowed by nature and shaped by selection. Because the trait is inborn and so pervasively effective, feeling healthy feels like “nothing” when we are young. We become aware of it only after we start losing it midlife. Roller-coaster rides begin to leave us nauseated instead of joyous. We can’t tolerate hot or cold weather like before. Sunny days feel too bright and reading menus in low lights becomes more difficult. Recovering from stressors—a late night, hangover, or injury—suddenly take far longer than it used to, if at all. Consider changes that wecan’t feel. When we are young, homeostatic capacity returns elevated blood glucose and blood pressure to base levels. As homeostatic capacity erodes with age, those levels may no longer self-tune. We call these conditions diabetes and hypertension, respectively. Indeed, the panoply of ailments associated with aging may be epiphenomena of eroding homeostatic capacity. If so, could restoring homeostatic capacity end or reverse aging?
HOMEOSTATIC CAPACITY AND AGING
The modern healthcare system is increasingly tasked with addressing the various ailments of aging. As we age, specific systems may fail to self-correct and report lag positions (e.g. high blood pressure, high blood glucose, or immune shift to Th-2 bias). The prevailing paradigm of the extant system is to center these out-of-balance positions. However, restoring homeostasis instead of homeostatic capacity fails to address the latter’s role in aging. As a result, although current healthcare system helps people live longer, its approaches also resemble a progressively futile game of Whack-a-MoleTM until everyone is ultimately dead. Furthermore, lifespan gains without fixing aging promote increasing per capita healthcare consumption, forming a vicious cycle of cost escalation that threatens to derail the global economy. We need a paradigmatic revolution. The aim of the prize is to catalyze that revolution by nurturing moonshot innovations that restore homeostatic capacity as a way of promoting longevity. The healthcare industry as we know it would contract dramatically, and a new system would emerge to help people live healthy and long lives.
HEART RATE VARIABILITY AS A BIOMARKER FOR HOMEOSTATIC CAPACITY
Homeostatic capacity comprises a multidimensional network of traits and operates at all scales of biology including at molecular, cellular, physiologic, organismal, and systems levels. For the purposes of the Prize, heart rate variability (HRV) was chosen as a biomarker of homeostatic capacity. Like many fields, the HRV field is not without controversy with differing points of view. On the positive side, HRV represents an intriguing biomarker for homeostatic capacity for the following reasons:
- HRV, a measure of cardiac autonomic function, is a proxy for autonomic nervous system function, one of the fundamental physiologic systems governing organismal homeostasis.
- HRV can be measured non-invasively and safely using a diverse array of tools a little variable cost.
- HRV measurement tools (including those available on personal mobile devices) already have a global footprint around the world.
- Autonomic dysfunction, as assessed by HRV, is associated with the panoply of aging diseases.
- Therapies that ameliorate the diseases of aging, reduce mortality rates, and improve longevity such as exercise, sleep, smoking cessation and caloric reduction have been shown to also improve HRV.
- Therapies that are known to promote health outcomes such as meditation, yoga, acupuncture and other alternative medicine treatments have been shown to improve HRV.
- Chronic stress, which has been shown to exacerbate diseases of aging, increase mortality rates, and shorten longevity, lowers HRV.
- HRV measurements via continuous fetal scalp monitoring have been used to prognosticate fetal distress and risk of mortality since 1965.
Will HRV prove to be a useful measure of homeostatic capacity? Is homeostatic capacity even the right trait on which to focus aging innovation? We don’t yet know the answers to these questions, but the most important thing is to start. We expect the path forward to offer surprises and disappointments. It may take many iterations of future prizes to ultimately crack and hack the aging code. Every step will likely offer more doors to open and more choices to make. In the meantime, we will learn. There’s one thing we’ve already learned by starting the Prize: the astounding ideas you’ve read in the public media represent just the tip of the iceberg. Initial round of conversations with leading scientists suggests that there are many ideas residing in the brains of brilliant minds that have not been shared. By starting the Prize now, we hope to accelerate these ideas into action. The cost of not acting now is breathtaking. Fatality rate from aging remains 100 percent. Yet the National Institute for Aging’s annual budget is only $1.04 billion, the lowest it has been in 10 years and only fraction of the annual R&D budget of many bio-pharmaceutical companies. Meanwhile, 150,000 people die of all causes everyday, the majority related in some way to aging. A million enter the queue each week. This is a race against time. The end of aging would be the end of healthcare as we know it. The end of aging would sever the feed-forward cost escalation cycle overwhelming the current healthcare system. If homeostatic capacity is restored and indefinitely sustained, humans would be able to persist at low annual-mortality rates currently enjoyed by young adults. Median lifespan could telescope to a number of years that might have once seemed unimaginable. Human capacity, thus, would finally be fully unleashed.