SOD mimicAEOL-10150 improve lifespan and delay brain aging via inhibition of senescence-associated secretory phenotype in SAMR1 strain

Xiao-rui ZHANG,Xiao-rui CHENG,Jian-hui WANG,Ju ZENG,Ding-ding MA,Hong-chao ZHANG,Wen-xia ZHOU,Yong-xiang ZHANG

(State Key Laboratory of Toxicology and Medical Countermeasures,Beijing Institute of Pharmacology and Toxicology,Beijing 100850,China)

T1-45

SOD mimicAEOL-10150 improve lifespan and delay brain aging via inhibition of senescence-associated secretory phenotype in SAMR1 strain

Xiao-rui ZHANG,Xiao-rui CHENG,Jian-hui WANG,Ju ZENG,Ding-ding MA,Hong-chao ZHANG,Wen-xia ZHOU,Yong-xiang ZHANG

(State Key Laboratory of Toxicology and Medical Countermeasures,Beijing Institute of Pharmacology and Toxicology,Beijing 100850,China)

OBJECTIVETo observe the anti-aging effects of SOD mimicAEOL-10150 in antisenescence accelerated mouse resistant 1(SAMR1)strain.METHODSThe lifespan of SAMR1 mice were observed by subcutaneous injection AEOL-10150 2 mg·kg-1once a week.Morris water maze,new object recognition,nesting and forced swimming were used to observe the behavioral changes of animals.Lymphocyte subgroups and ROS were measured by Flow cytometry.The cytokines levels were determined by Luminex method.The number of DCX+neurons in brain tissue was observed by immunofluorescence.RESULTSThe results showed that AEOL-10150 could prolong the mean lifespan of SAMR1 mice,but it had no obvious effect on maximal lifespan.What′s more,AEOL-10150 could significantly improve the spatial learning memory of aged mice,but it could not increase the number of DCX+neurons in the hypothalamic MBH and hippocampal DGregions.Then,we observed the effects of AEOL-10150 on peripheral blood lymphocyte subgroups and cytokines.We found that AEOL-10150 significantly modulated the lymphocyte subgroups and cytokine release.Especially,AEOL-10150 can dose-dependently inhibit plasma levels of SASP related inflammatory cytokines TNF-α and IL-17.CONCLUSIONThe results indicate that AEOL-10150 has anti-aging effects,and the effects are closely related to modulating immunity and inhibiting SASP production.

aging;mitochondria-targeted antioxidants;SOD mimic;SASP;endocrine

The project supported by Chinese Scientific and Technological Major Special Project(2014ZX09J13103-01B-003 and 2014ZX09J15104002)

Yong-xiang ZHANG,E-mail:zhangyx@bmi.ac.cn;Wen-xia ZHOU,E-mail:zhouwx@bmi.ac.cn