A Young Blood Environment Decreases Aging of Senile Mice Kidneys

Abstract

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 control (Ocon) groups, isochronic youth-youth group (Y-IP), elderly-elderly group (O-IP), and heterochronic youth (Y-HP) and elderly (O-HP) groups. 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 SA-β-gal in the O-HP group was significantly reduced compared with the Ocon and O-IP groups. Autophagy factors Atg5 and LC3BII were significantly upregulated, whereas 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 IL-6 and IL-1β were significantly reduced, whereas 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.

Reversing age: dual species measurement of epigenetic age with a single clock

“…Several decades ago, heterochronic parabiosis studies, in which the circulations of old and young mice were connected to instigate mixing of their blood, revealed that young blood can rejuvenate aging mice and vice versaold blood ages young mice 1 . A recent revival of this approach confirmed this observation and demonstrated beneficial effects on muscle, heart, brain, and numerous other organs [2][3][4][5][6][7] . Repeated injections of young plasma into older mice, an effective alternative to parabiosis, confirmed the prevailing notion that the beneficial effect is due to blood-borne factors; as opposed to the possibility that old mice might have, by proxy benefited from better-functioning organs of the young 8 .…”

“…Although parabiosis experiments showing organs of old mice to benefit biologically from sharing circulation with young ones were carried out decades ago, little follow-up work was done to capitalize on this remarkable observation until recently, when these experiments were successfully repeated and greatly expanded [1][2][3][4][5][6][7][8]10 . Young plasma transfer was shown to also work 8 .…”

Undulating changes in human plasma proteome across lifespan are linked to disease

“…Blood is a sensitive marker of functional aging but also plays an active role in aging. Numerous studies have shown that soluble factors from young mouse blood reverse aspects of aging and disease across multiple tissues [5][6][7][8][9][10][11][12][13]35 . Here, we describe a 46-protein aging signature that is conserved in humans and mice, containing several known aging proteins such GDF15 36 and IGF1/INSR 37 but also less investigated ones (Fig 1l).…”

“…Perhaps the strongest evidence that blood can be used to study aging comes from experiments employing heterochronic parabiosis, a surgically induced state in which the circulatory systems of young and old mice are joined. These studies show that multiple tissues, including muscle, liver, heart, pancreas, kidney, bone, and brain can be rejuvenated in old mice [5][6][7][8][9][10][11][12][13] . Plasma (the soluble fraction of blood) from old mice is sufficient to accelerate aspects of brain aging following repeated infusion into young mice 12 and young plasma can slow and reverse memory impairment and other aspects of brain aging 13,14 .…”

Regulation of Connective Tissue Growth Factor Expression by miR-133b for the Treatment of Renal Interstitial Fibrosis in Aged Mice with Unilateral Ureteral Obstruction

“…In our previous study, we found that miR-133b-3p was under-expressed in MSC-EVs of aged rats; however, miR-133b can inhibit the epithelial-mesenchymal transition (EMT) of renal tubular cells induced by transforming growth factor (TGF)-β1 [6]. We used a heterogeneous conjoined animal model and found that a younger blood environment could improve renal interstitial brosis in aging kidneys [19]. Therefore, we hypothesized that exosomes of bone marrow-derived mesenchymal stem cells might act as a humoral factor to affect renal interstitial brosis in the elderly.…”