Aging in the glomerulus

Abstract

Kidney function declines with age in the majority of the population. Although very few older people progress to end stage, the consequences of doing so are burdensome for the patient and very expensive for the society. Although some of the observed decline is likely due to changes in the vasculature, much is associated with the development of age-associated glomerulosclerosis. This article will review the well-established structural and functional changes in the glomerulus with age. The role of calorie restriction in modifying age-related pathology will be discussed. The importance of the podocyte as a critical cell in the aging process is considered using animal models and human biopsy material. Newer data on changes in gene expression driven by nuclear factor kappa beta (NFkB) and possible changes in biology in the glomerulus are discussed. The relationship between pathways involved in aging and the decline in kidney function is reviewed. There is speculation on the significance of these changes in relation to normal and pathological aging.

Figure 1.

Incident rates of treated end-stage kidney disease (eskd). Incident rates per million population per decade. Data obtained from U.S. Renal Data System (1).

Figure 2.

Aging glomeruli. Photomicrographs of glomeruli at different ages of ad-lib-fed and calorie-restricted rats developed with peroxidase GLEPP1 as a podocyte marker and counterstained with Periodic acid-Schiff and hematoxylin. The panels are all taken at the same magnification. Left: 2-month glomerulus. Center: 24-month calorie-restricted glomerulus. Right: an example of a partially sclerosed glomerulus at 24 months of age in the ad-lib-fed group. Note the increase in glomerular size and the expanded mesangial compartment in the ad-lib-fed older rats compared with calorie-restricted rats. The size bar in each photomicrograph is 50 µm long.

Figure 3.

Nuclear factor kappa beta (NFkB) binds the regulatory regions of glomerular genes. ChIP assays demonstrate that immunoprecipitation of NFkB–p50 protein coprecipitates the designated kB motif in the regulatory region of genes whose expression changes linearly with age in old versus young glomeruli. A nonspecific antibody of the same isotype is used as a control. ChiP = chromatin immunoprecipitation; VCAM = vascular cell adhesion molecule; ICAM = intercellular adhesion molecule.