Rapamycin treatment increases survival, autophagy biomarkers and expression of the anti-aging klotho protein in elderly mice.
Pharmacol Res Perspect
; 11(3): e01091, 2023 06.
Article
en En
| MEDLINE
| ID: mdl-37190667
ABSTRACT
Previous investigations have demonstrated that treatment of animals with rapamycin increases levels of autophagy, which is a process by which cells degrade intracellular detritus, thus suppressing the emergence of senescent cells, whose pro-inflammatory properties, are primary drivers of age-associated physical decline. A hypothesis is tested here that rapamycin treatment of mice approaching the end of their normal lifespan exhibits increased survival, enhanced expression of autophagic proteins; and klotho protein-a biomarker of aging that affects whole organism senescence, and systemic suppression of inflammatory mediator production. Test groups of 24-month-old C57BL mice were injected intraperitoneally with either 1.5 mg/kg/week rapamycin or vehicle. All mice administered rapamycin survived the 12-week course, whereas 43% of the controls died. Relative to controls, rapamycin-treated mice experienced minor but significant weight loss; moreover, nonsignificant trends toward decreased levels of leptin, IL-6, IL-1ß, TNF-α, IL-1α, and IGF-1, along with slight elevations in VEGF, MCP-1 were observed in the blood serum of rapamycin-treated mice. Rapamycin-treated mice exhibited significantly enhanced autophagy and elevated expression of klotho protein, particularly in the kidney. Rapamycin treatment also increased cardiomyocyte Ca2+ -sensitivity and enhanced the rate constant of force re-development, which may also contribute to the enhanced survival rate in elderly mice.
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Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Sirolimus
/
Proteínas Klotho
Límite:
Animals
Idioma:
En
Revista:
Pharmacol Res Perspect
Año:
2023
Tipo del documento:
Article
País de afiliación:
Hungria