Analysis of cell turnover in the macula densa through the normal aging process

The kidney undergoes changes during the lifespan of an individual, resulting in increased susceptibility to renal diseases in the elderly. The macula densa (MD) controls basic kidney functions, which deteriorate with aging. The present study for the first time, to the best of our knowledge, analyzed the relationship between cell proliferation and apoptosis (cell turnover) in the MD of mice through the normal aging process. Kidney specimens from CD1 mice aged 2, 6, 12, 18 or 24 months were fixed in neutral-buffered formalin and embedded in paraffin. Tissue sections were immunostained to analyze cell proliferation, subjected to a TUNEL assay to evaluate apoptosis, or stained with hematoxylin and eosin to determine total cell number. A markedly dynamic cell turnover pattern was observed in the MD throughout the aging process, in which, when the number of proliferating cells increased, the number of apoptotic cells decreased and vice versa. However, there were no significant differences in the total cell number among the ages analyzed. Thus, other mechanisms may be involved in the deterioration of renal functions regulated by the MD in elderly people. Further research is required to determine these mechanisms, which could be the target of therapeutic strategies against age-related kidney diseases in the future.