Exploring Splicing-Energy Axis Associations to Diet and Longevity

Area of Science:

• Biochemistry
• Genetics
• Aging Research

Background:

• Nutrient composition influences lifespan via mechanisms beyond calorie restriction.
• Mitochondrial regulation is a known factor in aging, but other pathways are emerging.
• Dietary interventions are key to understanding aging processes.

Purpose of the Study:

• To investigate the impact of a low-protein, high-carbohydrate diet on lifespan and cellular mechanisms.
• To explore the role of RNA splicing in mediating diet-induced longevity.
• To support the proposed "energy-splicing resilience axis."

Main Methods:

• Mice were fed a low-protein, high-carbohydrate diet enriched with cellulose.
• Liver proteome and RNA splicing patterns were analyzed.
• Connections between nutrient sensing, splicing factors (e.g., SRSF1), and signaling pathways (e.g., AMPK) were examined.

Main Results:

• The low-protein, high-carbohydrate diet extended lifespan in mice.
• This lifespan extension was associated with significant shifts in the liver proteome due to altered RNA splicing.
• The observed effects were distinct from those typically induced by caloric restriction and mitochondrial improvements.

Conclusions:

• Dietary interventions can promote longevity through RNA splicing modulation, independent of mitochondrial changes.
• The "energy-splicing resilience axis" provides a framework for understanding how cells adapt to nutritional stress via splicing.
• Targeting splicing pathways may offer novel strategies for promoting healthy aging and proteome stability.