PURPOSE: The SAM strains are a collection of inbred mouse strains developed as models of accelerated aging, and include nine short-lived, the senescence-prone strains(SAMP) and three longer lived control strains designated the senescence-resistant strains (SAMR).The SAMP was suggested as a new murine model of aging lung.However,molecular mechanism of accelerated lung aging remains to be elucidated.
METHODS: Quantitative real time RT-PCR and Western blot,image analysis of sliced lung tissue with H.E. stain
RESULTS: Here we show that expression of FOXO, a forkhead transcription factor that acts downstream of the PTEN/PI3K/Akt pathway and a key regulator of stress resistance, metabolism and ageing,was significantly decreased in aged SAMP mice compared to normal aging control SAMR mice. The decreased expression of FOXO gene was correlated with elevation of reactive oxidative species (ROS) and thiobarbituric acid reactive substances (TBARS),reduced mRNA expression levels of superoxide dismutase(SOD2) and catalase ,as well as greater mean line intercept(MLI) in SAMP mice lungs.
CONCLUSIONS: Based on these findings we concluded that reduced FOXO activity may contribute to accelerated lung aging in this animal model.
CLINICAL IMPLICATIONS: Given that FOXO proteins play a critical role in maintaining the quiescence and self-renewal capacity in hematopoietic stem cells and neural stem cells, manipulation of FOXO in lung progenitor cells may represent a novel approach to lung regenerative medicine and chronic lung disease such as COPD.
DISCLOSURE: The following authors have nothing to disclose: Yi-ming Yuan, Zhiguang Su, Xiuyin Hu, Li Luo, Ming Yang
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