Renal Aging Resembles a Continuum Between Normal and Diseased Kidneys That Potentiates Inflammatory Response to...

Renal aging is a natural process that can lead to structural changes and functional decline in the kidneys. These age-related changes are considered irreversible physiological processes, but resemble diseased kidneys. To enhance understanding of the molecular nature of renal aging, we first compared whole-kidney RNA sequencing between naturally aging mice (24-month-old) and adenine-induced nephropathy in young mice (2-month-old). Young mice (2-month-old) without intervention were used as the control group to investigate transcription alteration with aging or by adenine-enriched diet. Next, we compared the functional and structural renal consequences of aging and adenine-induced nephropathy between young (2-month-old) and old mice (18- to 22-month-old). C57BL/6 male mice were used in all experimental studies. Both aging kidneys and adenine-induced nephropathy showed similar transcriptional profiles characterized by upregulation in innate and adaptive immune system activation and inflammation, although these alterations were generally less significant in the aging kidneys. In contrast to aging kidneys, adenine-induced nephropathy showed prominent expression of the genes related to cytokines, T-cell activation, and fibrosis and decreased expression of the genes implicated in transporter activity and metabolism. The subclinical immunological micromilieu in aging kidneys potentially causes augmented kidney damage in response to injurious stimulus. When mice were fed with adenine-enriched diet, aging kidneys showed more extensive tubular injury and fibrosis with stronger inflammatory response than young kidneys. Taken together, our results suggest that renal aging may lie on a continuum between normal kidneys and diseased kidneys in the context of immune system upregulation that can worsen kidney damage upon injury.