Engineering ATP Import in Yeast Uncovers a Synthetic Route to Extend Cellular Lifespan

Area of Science:

• Gerontology
• Cellular Biology
• Metabolism

Background:

• Aging is linked to molecular damage and declining cellular energy production, specifically adenosine triphosphate (ATP).
• The direct causal link between ATP homeostasis and the aging process remains unclear.
• Understanding energy metabolism's role in aging is crucial for developing longevity strategies.

Purpose of the Study:

• To investigate the direct impact of cellular adenosine triphosphate (ATP) homeostasis on lifespan.
• To establish a causal relationship between ATP levels and aging in a model organism.
• To explore energy metabolism as a potential target for anti-aging interventions.

Main Methods:

• Utilized a novel method involving a nucleotide transporter from a eukaryotic intracellular parasite to import extracellular ATP into budding yeast.
• Manipulated intracellular ATP levels by supplementing or depleting extracellular ATP.
• Performed gene expression analysis to understand the molecular effects of altered ATP levels.

Main Results:

• Depletion of intracellular ATP significantly reduced yeast lifespan.
• Supplementation of extracellular ATP fully restored and extended yeast lifespan.
• Elevated ATP levels were found to inhibit catabolic processes, including glucose metabolism.

Conclusions:

• Cellular ATP homeostasis directly regulates lifespan, establishing a causal link previously untested.
• Energy metabolism plays a critical role in the aging process.
• Targeting cellular energy production presents a promising avenue for longevity interventions.