Crocetin delays brain and body aging by increasing cellular energy
levels and enhances the median life span in aged C57BL/6J mice
Abstract
Abstract Background and Purpose Aging is usually accompanied by
mitochondrial dysfunction, reduced energy levels, and cell death in the
brain and other tissues. Mitochondria play a crucial role in maintaining
cellular energy through oxidative phosphorylation (OXPHOS). However,
OXPHOS is impaired as mitochondrial oxygen supply decreases with age. We
explored whether pharmacologically increased oxygen diffusion by
crocetin can restore OXPHOS and help delay aging of brain and other
vital organs. Experimental Approach Stress-free chronic treatment of
aged C57BL/6J mice with crocetin followed by an analysis of behavior,
hippocampi whole transcriptome, and key energy metabolites by LCMS was
performed. Key Results The aged mice treated with crocetin for four
months displayed significantly improved memory behavior, neuromuscular
coordination, and ATP and NAD+ levels in the brain and other vital
organs, leading to an increased median life span. The transcriptomic
analysis of hippocampi from crocetin-treated mice revealed that enhanced
brain energy level was caused by the upregulation of genes linked to
OXPHOS, and their expression was close to the expression in young mice.
The chronic treatment of aged astrocytes also showed improved
mitochondrial membrane potential and energy state of the cells.
Conclusion and Implications Our data suggest that restoring the OXPHOS
and the normal energy state of the cell can delay aging and enhance
longevity. Therefore, molecules like crocetin should further be explored
to treat age-related diseases.