A Small Molecule NAMPT Activator to Reverse Age-Dependent Decline in NAD+
2021 Harrington Scholar-Innovator
Good health is the wish traditionally conveyed by toasts in cultures around the world. Dr. Finkel, however, is doing more than simply raising a glass and wishing; he is conducting research into aging with the goal of helping humans remain healthier longer.
Nicotinamide adenine dinucleotide (NAD+) is a critical coenzyme found in every cell of the human body, and is involved in hundreds of metabolic processes. Aging is associated with a decline in tissue NAD+ levels, and this decline has been linked to various age-related diseases.
Dr. Finkel and his colleagues are researching the effects of restoring NAD+ levels with a small molecule that augments the activity of NAMPT, the enzyme that controls NAD+ levels. Boosting or restoring NAD+ levels could represent a potential preventive therapy for a wide range of age-related diseases.
Dr. Finkel and his team developed an innovative screening platform to identify— from an initial library of more than 100,000 compounds—a set of small molecules that directly bind to NAMPT. They further determined that a subset of these binding molecules can potently augment NAMPT activity. This approach thereby represents a novel overall strategy to modulate NAD+ levels.
Dr. Finkel is quick to point out that this research is not a quest for the mythical Fountain of Youth.
“We're not really trying to extend lifespan,” Dr. Finkel says. “We're trying to expand ‘health span,' which is basically the time that individuals live free of diseases. The goal is to identify targets that link aging and disease and reduce the diseases and morbidities individuals face in their last few decades.”