Biomaterial Database

Short term treatment with a cocktail of rapamycin, acarbose and phenylbutyrate delays aging phenotypes in mice. 2022

Zhou Jiang, and Juan Wang, and Denise Imai, and Tim Snider, and Jenna Klug, and Ruby Mangalindan, and John Morton, and Lida Zhu, and Adam B Salmon, and Jackson Wezeman, and Jiayi Hu, and Vinal Menon, and Nicholas Marka, and Laura Neidernhofer, and Warren Ladiges

Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA, USA.

Pharmaceutical intervention of aging requires targeting multiple pathways, thus there is rationale to test combinations of drugs targeting different but overlapping processes. In order to determine if combining drugs shown to extend lifespan and healthy aging in mice would have greater impact than any individual drug, a cocktail diet containing 14 ppm rapamycin, 1000 ppm acarbose, and 1000 ppm phenylbutyrate was fed to 20-month-old C57BL/6 and HET3 4-way cross mice of both sexes for three months. Mice treated with the cocktail showed a sex and strain-dependent phenotype consistent with healthy aging including decreased body fat, improved cognition, increased strength and endurance, and decreased age-related pathology compared to mice treated with individual drugs or control. The severity of age-related lesions in heart, lungs, liver, and kidney was consistently decreased in mice treated with the cocktail compared to mice treated with individual drugs or control, suggesting an interactive advantage of the three drugs. This study shows that a combination of three drugs, each previously shown to enhance lifespan and health span in mice, is able to delay aging phenotypes in middle-aged mice more effectively than any individual drug in the cocktail over a 3-month treatment period.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D010641	Phenotype	The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.	Phenotypes
D010654	Phenylbutyrates	Derivatives of 4-phenylbutyric acid, including its salts and esters.
D005260	Female		Females
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D020123	Sirolimus	A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.	Rapamycin,AY 22-989,I-2190A,Rapamune,AY 22 989,AY 22989,I 2190A,I2190A
D020909	Acarbose	An inhibitor of ALPHA-GLUCOSIDASES that retards the digestion and absorption of DIETARY CARBOHYDRATES in the SMALL INTESTINE.	Bay g 5421,Glucobay,Glucor,Glumida,Prandase,Precose