Characterization of cellular senescence in doxorubicin-induced aging mice

With a rise in the need to develop anti-aging drugs, a growing number of in vivo studies evaluating the efficacy of potential drug candidates have used doxorubicin-induced aging mice. However, changes in the biomarkers of senescent cells have not been reported in detail in these animals. To lay a foundation for the use of doxorubicin-induced aging mice, we examined the biomarkers of hepatic and renal senescent cells in these mice. We found that the 5 mg/kg doxorubicin dose is optimal to induce cellular senescence in mice. Subsequently, using this dose, we found that doxorubicin-induced an increase in senescence-associated beta-galactosidase (SA-beta-gal) positive cells in the kidney and lipofuscin accumulation in the liver. Some markers of senescent cells (p21(WAF1/CIP1), p16(INK4A), and gamma H2AX) were also significantly upregulated by doxorubicin and then counteracted by metformin treatment. These preliminary findings support the application of doxorubicin-induced aging mice as an animal model to evaluate the efficacy of anti-aging drug candidates.

Automated summary

By studying a mouse model of doxorubicin-induced aging, we found that a dose of 5 mg/kg of doxorubicin was optimal for inducing cellular senescence in mice. This dose led to an increase in senescent cells and the accumulation of lipofuscin in the kidney and liver, respectively. These preliminary findings support the use of doxorubicin-induced aging mice as an animal model for evaluating potential anti-aging drug candidates.