One of the main goals of aging research is to discover interventions that can prolong lifespan and healthspan, the healthy years of life. In the current proposal we focus on a novel treatment toward this end: the restriction of phosphate and potassium in the diet. Against a backdrop of landmark studies of lifespan extension under restriction of carbon and sulfur, the role of dietary phosphate and potassium has been almost completely passed over by the aging research community. In preliminary experiments using yeast as a model system, we have seen that phosphate and potassium restriction extends lifespan up to 24% relative to standard conditions. This effect is a particularly compelling target for aging research focused on human health, since any clinical applications could make use of currently available drug mimetics of phosphate and potassium starvation. To enable any such translational undertaking, however, we must know enough about the longevity evoked by these regimens to design effective treatments. We propose to use invertebrate model systems for a series of rapid, relatively cheap, and conclusive experiments to establish which phosphate and potassium binder drugs extend lifespan and how.
In Aim 1 we screen these drugs in yeast using a rigorous microfluidic system for lifespan assays, and we investigate the mechanisms by which genetic and environmental micronutrient starvations exert their effects.
In Aim 2 we screen the most compelling drugs for effects on lifespan and healthspan in nematode worms. Together, these experiments will serve as a springboard for the testing of pro- lifespan, pro-healthspan treatments and genes in mammalian systems.

Public Health Relevance

Treatments to promote healthy aging are an urgent need in the clinic. We have discovered that yeast starved for phosphate and potassium are strikingly long-lived, dovetailing with previous reports of longevity of mice and flies in which phosphate uptake is disrupted. In the current proposal, we use yeast and worms as models to dissect how interventions that trigger the phosphate and potassium starvation responses can extend lifespan.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Small Research Grants (R03)
Project #
1R03AG056938-01
Application #
9379421
Study Section
Cellular Mechanisms in Aging and Development Study Section (CMAD)
Program Officer
Williams, John
Project Start
2017-07-01
Project End
2019-05-31
Budget Start
2017-07-01
Budget End
2018-05-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Buck Institute for Age Research
Department
Type
DUNS #
786502351
City
Novato
State
CA
Country
United States
Zip Code
94945