Effects Of Internal Environment Change On Kidney Aging Caused By Kidneys Transplantation Between Young And Old Rats

Background Genomic background,environmental effects and their interactions are the main cause of aging.Organs live in the internal environment of the body.A specific organ,like kidney,live in different internal environment when the body young and old,the hemodynamics,and blood components will be more different.The genomic background of an organ is relative permanent;we speculated that,aging of organ,like kidney,was a result of abnormality of genomic regulation caused by aged internal environment,as the body aging.The mechanism of organ aging is not clear now.Objective We developed a new method which transplanted young and old Fisher-344 rats' kidneys into each other. Without immune rejection in the same strain,and with the same feeding conditions,we focused on the effects of the internal environment change on the isograft.The purpose was to uncover the molecular biologic changes of the kidney when it was putted into a "younger" or "older" internal environment,and the genomic changes at expression level.To answer the question that whether the young kidney changed into "older" in the "old" internal environment,or old kidney changed into "younger" in the "young" internal environment.Methods Young(4 months)and aged(16 months)male Fisher-344 rats underwent left kidney orthotopic transplantation to each other.Age-matched sham-operated rats served as controls.Rats were sacrificed at 3 months later,blood systolic pressure, body weight,serum TP,ALB,TG,CH,and kidney weight,pathological changes, SA-β-gal(senescence-associatedβ-galactosidase),Sirt-1(silent information regulator)expression were measured,and the transplanted kidney's glomerular filtration rate(GFR)was evaluated.Whole genome expression spectrum was uncovered by gene microarray.Results There was no significant difference in body weight,systolic pressure,serum TP,ALB,TG,CH,kidney weight,and left kidney GFR,(P＞0.05).There was no significant difference in glomerular sclerosis index(GSI)and SA-β-gal positive rate in the same chronological age kidney,but significant difference in tubulointerstitial lesions(TIL)between transplanted kidney and the sham operated kidney.The interesting thing was that the GSI,TL and SA-β-gal positive rate increased in YO than in YY,and decreased in OY than in OO,but the changes were not significant.Sirt-1 decreased in the transplanted kidney(P＜0.05),and the expression in OY was less decreased than in OO,the changes were not significant.548 gene expressed differentially between 7 and 19 month normal rat kidney,up-regulated 36,and down-regulated 512(Ratio＞2).Old internal environment up-regulated 127,and down-regulated 365 genes of young kidney.And young internal environment up-regulated 680, down-regulated 574 genes of old kidney.The affected pathways of young/old internal environment on old/young kidney were similar,included energy metabolism,ECM,proliferation,and apoptosis,the effects were reverse. Conclusions The transplanted "younger" or "older" kidney had no effects on receptor rat;the new internal environment had no effects on the transplanted kidney in morphology,and function,except the ischemia/reperfusion injury effects on tubular-interstitium.We did find that young kidney had a trend to be more senescecent in the old intemal environment,and the old kidney had a trend to be younger in the young internal environment.We found significant effects of new internal environment on transplanted kidney at gene expression level, especially in the energy metabolism system,ECM(extracelluar matrix)and proliferation pathway.Old internal environment facilitated these genes in young kidney expressed like old kidney,and young internal environment facilitated these genes in old kidney expressed like young kidney.Our results provided new data to help understanding the basement biological mechanism in the aging process,and instructed the approach to find key factors and molecular markers in kidney aging.