Our Measurements and Tests Aren’t Revealing What Is Actually Causing Many Diseases
Our understanding of human physiology and disease remains incomplete. In the last century, we have developed cures for many diseases with well-defined root causes (polio, smallbox, cholera, SMA, cervical cancer, etc.). However, a wide array of conditions still eludes cures and treatments. We have yet to fully decipher the dynamic interplay between brain and peripheral systems, the bioenergetic processes underlying chronic conditions, and the multifactorial pathways that drive aging. The biological mechanisms driving complex diseases and the aging process are multifactorial, involving multiple interacting pathways.
Although we understand some individual aging mechanisms, we do not yet have line of sight to comprehensively rejuvenating mammals or extending lifespan. To overcome these challenges, we need combinatorial approaches that can modulate multiple mechanisms simultaneously, allowing us to measure multi-system impacts and develop effective interventions.
Foundational Capabilities (10)
Map the connectivity not only within the brain but also between the brain and peripheral organs to reveal integrated regulatory networks.
To study interactions in complex systems we need to measure multiple agents simultaneously, ideally with timecourse data. Doing this in live aged organisms would require new tools.
Develop aging-relevant in vitro models and screen combinations of interventions (e.g., small molecules, gene therapies) using multi-omic and functional readouts to identify synergistic treatments that extend lifespan or promote regeneration.
Develop immortal model organisms beyond cell lines to enable the study of longevity and underlying mechanisms of aging.
Implement pooled screening techniques directly in living organisms to test multiple intervention combinations concurrently in aged context, accelerating discovery in complex disease and aging research.
Create detailed, functional maps of hypothalamus/brainstem activation by specific peptides and hormones to link neural activity with physiological outcomes and decipher how the brain orchestrates complex physiological responses.
Study and engineer endosymbiotic relationships (e.g., mitochondria) to better understand and manipulate cellular energy production, potentially offering new avenues to treat bioenergetic disorders.
Integrated analytic tools to study clinical, molecular, and environmental datasets to identify patterns and infer the underlying causes of disease.