The molecular basis of age-related kidney disease.
Renal disease affects 11% of people in the United States over the age of 65, not including those with diabetes or hypertension. Although glomerular disease is the most common underlying etiology of age-related renal dysfunction, the cause of glomerular disease and whether it is the only contributor to renal failure are not known. Our studies in female mice show that renal disease in the postmenopausal period is associated with progressive glomerular enlargement and scarring, as well as abnormal renal function. To study the underlying causes of aging-related glomerular disease, we isolated and characterized glomerular smooth muscle (mesangial) cells from female mice of various ages. We found that the cells from older mice exhibit a variety of phenotypic changes, including increased concentrations of p27, a protein that serves to inhibit progression from the G1 to the S phase of the cell cycle. Because the bone marrow (BM) contains mesangial cell progenitors that can transfer the donor glomerular phenotype (normal or diseased) to recipients, we exchanged BM between postmenopausal and premenopausal mice and found that aging-related glomerular enlargement and scarring are transferred to young recipient glomeruli. In addition, BM from normal, young donors led to the regression of aging-related glomerular disease in postmenopausal recipients; namely, both glomerular enlargement and scarring were reduced. Thus, aging-related glomerular disease is an entity distinct from all other causes of renal disease, is characterized by phenotypic changes in mesangial cell progenitors, and is reversible when the phenotype of the progenitors is returned to normal.
Zheng
Feng
F
Department of Medicine, Vascular Biology Institute, University of Miami, Miami, FL 33136, USA.
Plati
Anna Rita
AR
Banerjee
Anita
A
Elliot
Sharon
S
Striker
Liliane J
LJ
Striker
Gary E
GE
D000368:Aged; D000375:Aging / Q000235:genetics / Q000473:pathology; D000818:Animals; D005260:Female; D006801:Humans; D015994:Incidence; D007674:Kidney Diseases / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D017698:Postmenopause; D014481:United States / Q000453:epidemiology