In parabiosis studies, a young and old animal have their circulatory systems linked. This is shown to improve measures of aging in the old animal, such as regenerative capacity, stem cell activity, and so forth. There is considerable debate over the mechanisms involved, with the current balance of evidence favoring a dilution of harmful factors and signals present in old blood and tissues rather than a delivery of beneficial factors and signals present in young blood.
In the research reported here, the authors examine the effects of parabiosis on the function of aged kidneys. It is too early to say what this will add to the discussion of specific mechanisms, but speculation is certainly possible. Even given the consensus, it has to be said that the data looks a lot one might expect to see if young immune cells are coming in and doing a better job of reducing the senescent cell burden in an aged kidney than the native, old immune system is capable of achieving. Yet it is also possible that simply altering the balance of factors in the surrounding environment spurs more of these unwanted and harmful cells to self-destruct on their own, given that they are already primed for apoptosis.
Whether changes in internal body environment affect kidney aging remains unclear. Specifically, it is unknown whether transplanted kidneys from older donors recover from tissue damage after placement in younger recipients. In this study, a parabiosis animal model was established to investigate the effects of a young internal body environment on aged kidneys.
The animals were divided into six groups: young (Ycon) and old (Ocon) control groups, isochronic youth-youth group (Y-IP), elderly-elderly group (O-IP) and heterochronic youth (Y-HP) elderly (O-HP) group. After parabiosis, tubule and interstitial tissue scores in the O-HP group were significantly lower than in the Ocon and O-IP groups. The expression of aging-related protein p16 and senescence-associated β-galactosidase in the O-HP group was significantly reduced compared with the Ocon and O-IP groups. Autophagy factor Atg5 and LC3BII were significantly upregulated, while the expression of the autophagic degradation marker (P62) was significantly downregulated in the O-HP group compared with the Ocon and O-IP groups.
With the same comparison, the positive cells of TUNEL staining and the expression of inflammatory cytokines IL-6 and IL-1β were significantly reduced, while the total/cleaved caspase-3 and total/pNF-κB were significantly increased in the O-HP group. The results demonstrated that a young blood environment significantly reduces kidney aging. These findings provide new evidence supporting an increase in the upper age limit for human kidney transplantation donors.