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Rapamycin treatment during development extends life span and health span of male mice and Daphnia magna. 2022

Anastasia V Shindyapina, and Yongmin Cho, and Alaattin Kaya, and Alexander Tyshkovskiy, and José P Castro, and Amy Deik, and Juozas Gordevicius, and Jesse R Poganik, and Clary B Clish, and Steve Horvath, and Leonid Peshkin, and Vadim N Gladyshev
Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Development is tightly connected to aging, but whether pharmacologically targeting development can extend life remains unknown. Here, we subjected genetically diverse UMHET3 mice to rapamycin for the first 45 days of life. The mice grew slower and remained smaller than controls for their entire lives. Their reproductive age was delayed without affecting offspring numbers. The treatment was sufficient to extend the median life span by 10%, with the strongest effect in males, and helped to preserve health as measured by frailty index scores, gait speed, and glucose and insulin tolerance tests. Mechanistically, the liver transcriptome and epigenome of treated mice were younger at the completion of treatment. Analogous to mice, rapamycin exposure during development robustly extended the life span of Daphnia magna and reduced its body size. Overall, the results demonstrate that short-term rapamycin treatment during development is a novel longevity intervention that acts by slowing down development and aging, suggesting that aging may be targeted already early in life.

UI MeSH Term Description Entries
D008136 Longevity The normal length of time of an organism's life. Length of Life,Life Span,Lifespan,Life Spans,Lifespans
D008297 Male Males
D003621 Daphnia A diverse genus of minute freshwater CRUSTACEA, of the suborder CLADOCERA. They are a major food source for both young and adult freshwater fish. Daphnias
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
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
D061385 Insulins Peptide hormones that cause an increase in the absorption of GLUCOSE by cells within organs such as LIVER; MUSCLE and ADIPOSE TISSUE. During normal metabolism insulins are produced by the PANCREATIC BETA CELLS in response to increased GLUCOSE. Natural and chemically-modified forms of insulin are also used in the treatment of GLUCOSE METABOLISM DISORDERS such as DIABETES MELLITUS.
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

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