Fig. 7: Schematic model for α-KB-mediated longevity.
From: The metabolite alpha-ketobutyrate extends lifespan by promoting peroxisomal function in C. elegans
Supplementation with exogenous α-ketobutyrate (α-KB) increases the NAD+ contents via LDH-1. The NAD+-SIR-2.1/SIRT1 signaling enhances peroxisome function and biogenesis, thus leading to the upregulation of acox-1.2/ACOX1, a key gene in the peroxisomal fatty acid β-oxidation pathway. ACOX-1.2/ACOX1 promotes the production of H2O2, which in turn activates SKN-1/NRF2. This transcription factor induces autophagy by regulating the expressions of autophagic and lysosomal genes at a transcription level. Increased autophagic activity promotes longevity and delays cellular senescence.
