Background: Given the growing challenges posed by an ageing population, particularly in Western countries, we aimed to investigate the potential geroprotective effects of resveratrol and melatonin in ageing rats. Methods: The animals were treated with these two compounds starting at 3 months of age and continuing until 1 year or 2 years of age. Using a multibiomarker approach, we assessed DNA damage, telomere length, and the oxidative status in their urine, liver, and kidneys. Results: Despite employing this experimental approach, our results did not provide conclusive evidence of geroprotective effects across the evaluated organs. However, we observed sex-dependent differences in response to treatment. Conclusions: Given the high potency of these two compounds, further research is warranted to explore their incorporation into daily routines as a strategy to mitigate ageing-related effects.

The anti-aging gene/protein Klotho (Kl), most present in kidneys, has been well studied in mice (mKl), but not in rats (rKl). This study investigated the renal rKl expression in male and female rats. Sex-related measurement of rKl-controlled electrolytes was performed in plasma/urine samples, as were tests on species differences in renal Kl expression (rats vs. mice). rKl mRNA/protein expression was studied by qRT-PCR/Western-blotting in renal total RNA/cell membranes and its localization by immunofluorescence microscopy. Urine/plasma ions (phosphate/total calcium) and macroelements (phosphorus/calcium) were measured biochemically and by ICP-MS, respectively. In rat kidneys, the rKl mRNA/protein was detected in the cortex, outer and inner stripe but not in the papilla, and was immunolocalized in the basolateral membrane of proximal tubules in the cortex and outer stripe, but not in the intercalating cells of the cortical distal tubules, whereas mKl was observed in the mouse kidney cortex but not the outer stripe. Female-dominant expression of renal rKl, affected by androgen’s inhibitory effect, may have contributed to the sex-related level of urine electrolytes, particularly phosphates. Renal mKl expression was male-dominant. Sex- and species-related differences in renal Kl expression may be relevant for the selection of the sex and/or the model organism in studies addressing aging/mineral homeostasis.