A cocktail of rapamycin, acarbose and phenylbutyrate prevents age-related cognitive decline in mice by altering aging pathways

A recent study showed that middle-aged mice treated with a drug cocktail of rapamycin, acarbose, and phenylbutyrate for three months had increased resilience to age related cognitive decline. This finding provided the rationale to investigate the comprehensive transcriptomic and molecular changes within the brain of mice that received this cocktail treatment or control substance. Transcriptome profiles were generated through RNA sequencing and pathway analysis was performed by gene set enrichment analysis to evaluate the overall RNA message effect of the drug cocktail. Molecular endpoints representing aging pathways were measured through immunohistochemistry to further validate the attenuation of brain aging in the hippocampus of mice that received the cocktail treatment, each individual drug or controls. Results indicated that biological processes that enhance aging were suppressed, while autophagy was increased in the brains of mice given the drug cocktail. The molecular endpoint assessments indicated that treatment with the drug cocktail was overall more effective than any of the individual drugs for relieving cognitive impairment by targeting multiple aging pathways.

Full Paper:

2022.09.07.506968v1.full.pdf (538.1 KB)

1 Like

I have this image of mice doing The NY Times crossword. How the heck do they measure cognitive ability in mice and it’s decline? They used to throw the poor suckers into a pool to see if they would swim to the edge, but I think that’s been ruled unethical.

I think its a timed maze test:

Learning parameters were measured by a spatial navigation learning task [13]. Old mice that received cocktail and Rap showed enhanced learning abilities compared to all other cohorts. Rotarod, which exploits a mouse’s natural avoidance to height, was used to assess motor coordination [14]. Only mice treated with the cocktail showed significantly better performance. Both tests indicated that the drug cocktail was phenotypically effective suggesting a more robust effect than any individual drug.