Study On The Regulation Of Hemocyte Hsp23/27 On The Aging Of Heart In Drosophila

Background:With the increasing aging of the population, aging has become a hot topic. Aging is a process of gradual decline of the function of the organ system in the body. The heart is one of the most important organs of the human body. Intrinsic cardiac ageing is defined as a slow and progressive worsening of function, structure, and rhythmicity that accompanies with age. Cardiac aging is associated with a variety of cardiovascular diseases. How to prevent the occurrence and development of cardiovascular disease and how to reverse cardiovascular disease caused by cardiac aging has become a current research hot spot.Small heat shock proteins (sHSPs) are conserved across species and function as chaperons to maintain proper protein conformation during stress. Hsp27 is one of the most important members of the family of sHSPs. It has reported that Hsp27 is closely related to cardiovascular disease, Hsp27 can protected cardiac function against various stressful conditions. The present study found that as cardiovascular disease occurs in serum content of Hsp27 also changed.Objective:We aimed to describe the association between Hsp27 in hemese and cardiac function.Methods:1、We crossed RNAi lines targeting Drosophila Hsp27/23 (UAS-Hsp27i/ UAS-Hsp23i) and UAS-Hsp27/23 transgene lines with a hemocyte-specific Hemese-GAL4 driver to investigate the function of hemocyte Hsp27/23 in cardiac ageing、 structure、lifespan、glucolipid metabolism and 4EBP m RNA level.2、We test the cardiac function、structure、lifespan、p-4EBP protein level and 4EBP m RNA level of RNAi lines targeting Drosophila Hsp27 after Rapamycin treatment two weeks later.3、We generate flies with hemocyte specific knockdown of Hsp27, but with over-expression of d4EBP() to test the cardiac function.Results1、Hsp27 expression is down-regulated in heart tubes during cardiac ageing。2、Hemocyte knockdown of sHSPs resulted in accelerated cardiac ageing(P< 0.05) and lifespan shortening(P< 0.001), while over-expression of sHSPs protects heart against HFD-induced cardiac dysfunction (P<0.05). In whole animal level, the expression of Hsp27/Hsp23 is negatively correlated with TOR activity.3、Rapamycin treatment or hemocyte specific 4EBP over-expression alleviates cardiac dysfunction caused by hemocyte specific Hsp27 knockdown.Conclusion:These results demonstrated a clear link between hemocyte sHSPs and cardiac ageing in a transgenic flies model. Futhermore Hsp27 protected cardiac function through regulating TOR/4EBP signaling. Our findings reveal a potent anti cardiac ageing therapeutics via regulating sHSPs in blood.