Time-restricted feeding for five weeks does not improve renal injury markers in aged male mice

Aging is associated with a decline in kidney function and increased susceptibility to renal injury and fibrosis. Several factors contribute to age-related structural changes and functional decline in the kidney. Time-restricted feeding (TRF) has potential anti-aging properties, but its effect on kidney health is unclear. The objective of this study is to determine the impact of TRF on kidney function and health in aged mice. We hypothesize that TRF will improve markers of kidney function and injury in aged mice compared with ad libitum (AL) age-matched mice. Male C57BL/6 mice, aged 6 and 18 months, were fed an AL high-salt diet (4.0% NaCl). A subset of aged mice was placed on a TRF schedule (8-hour feeding window during the active period) for five weeks. Tissues were collected at the beginning of the inactive period of the mice at the end of the feeding schedule. Immunohistochemistry was performed to assess the structural integrity of glomeruli. Daily food intake and activity levels were similar between AL and TRF groups in aged mice (N=5-6). Renal injury biomarkers kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were assessed using multiplex immunoassay and immunoblotting, respectively. Cortical KIM-1 levels were higher in TRF mice compared to AL (P=0.05). Cortical KIM-1 concentration was also higher in aged mice compared to the young (P=0.0002; young AL: 17 ± 3; aged AL: 106 ± 15; aged TRF: 202 ± 39 pg/mL/protein; N=5-6). Medullary KIM-1 levels following TRF were similar to AL in aged mice (P=NS); however, KIM-1 increased in aged mice compared to young (P=0.001). Medullary NGAL expression was similar following TRF in aged mice and in aged vs young mice (P=NS). Similarly, there was no effect of TRF or age on serum creatinine and blood urea nitrogen levels (P=NS). Nephrin staining was used to assess glomeruli count and area. Glomerular quantity was not affected by TRF or age (P=NS; N=5-6). Glomerular size was similar following TRF compared to AL in aged mice (P=NS). Aged AL mice had larger glomeruli on average than young mice (P=0.04; young AL: 244 ± 18; aged AL: 318 ± 27; aged TRF: 279 ± 20 pixels/glomerular number; N=5-6). In conclusion, aging led to increased levels of particular kidney injury markers in mice on a high salt diet. However, TRF did not improve any of these markers in aged mice. Interestingly, KIM-1 was higher following TRF in aged mice. Future studies will determine the causes of this increase and whether kidney function is affected in response to TRF. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.