Like other organs in the body, the kidneys undergo age-associated anatomical, structural and physiological changes. Starting at 50 years of age, there is a 3-10% decline in kidney weight for each subsequent decade of life, with the loss of cortical mass greater than medullary mass. In fact, the number of glomeruli start to decrease progressively after age 40, and the number of sclerotic glomeruli increases, making the distinction between involutional and disease-related sclerosis unclear in some cases. The outer cortical glomeruli are, in general, more extensively involved than deeper glomeruli, but glomerular size does not change. In general, the loss of the glomerular mass is proportional to the loss of tubular mass, maintaining glomerulotubular balance. In addition to glomerular sclerosis, there is a gradual increase in interstitial fibrosis, and there is focal thickening of both glomerular and tubular basement membranes, probably due to the accumulation of type IV collagen.