Journal
AGING CELL
Volume 20, Issue 5, Pages -Publisher
WILEY
DOI: 10.1111/acel.13345
Keywords
17α ‐ estradiol; acarbose; aging; protein translation; rapamycin; signal transduction
Categories
Funding
- National Institutes of Health [AG022303, AG024824]
- Paul F. Glenn Center for Biology of Aging Research at the University of Michigan
Ask authors/readers for more resources
The study suggests that rapamycin and acarbose can prevent age-related declines in cap-independent translation (CIT) target proteins in both sexes, while 17 alpha-estradiol has a similar effect only in males. The activity of mTORC1 is blocked by rapamycin, acarbose, and 17 alpha-estradiol in age-related increases. The increase in METTL3 activity and CIT-dependent proteins may represent a shared pathway for both long-lived mutant mice and drug-induced lifespan extension in mice.
We hypothesized that rapamycin (Rapa), acarbose (ACA), which both increase mouse lifespan, and 17 alpha-estradiol, which increases lifespan in males (17aE2) all share common intracellular signaling pathways with long-lived Snell dwarf, PAPPA-KO, and Ghr-/- mice. The long-lived mutant mice exhibit reduction in mTORC1 activity, declines in cap-dependent mRNA translation, and increases in cap-independent translation (CIT). Here, we report that Rapa and ACA prevent age-related declines in CIT target proteins in both sexes, while 17aE2 has the same effect only in males, suggesting increases in CIT. mTORC1 activity showed the reciprocal pattern, with age-related increases blocked by Rapa, ACA, and 17aE2 (in males only). METTL3, required for addition of 6-methyl-adenosine to mRNA and thus a trigger for CIT, also showed an age-dependent increase blunted by Rapa, ACA, and 17aE2 (in males). Diminution of mTORC1 activity and increases in CIT-dependent proteins may represent a shared pathway for both long-lived-mutant mice and drug-induced lifespan extension in mice.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available