Age and sex modulate renal expression of SGP-2 and transglutaminase and apoptosis of splenocytes, thymocytes, and macrophages.
BACKGROUND
Aging in humans has been associated with the progressive loss of renal mass. This has been considered to account for a significant reduction of glomerular filtration rate in the aging population. In addition, aging is associated with a compromised immune system. Macrophages, thymocytes, and splenocytes play an important role in the maintenance of the immune system. We studied the effect of sex and aging on apoptosis of peritoneal macrophages, thymocytes, and splenocytes. In addition, we also studied the effect of sex and aging on mRNA expression of active cell death genes on the renal cortex.


METHODS
Rats in groups of 4 to 12 were killed at ages 2, 14, 30, 50, 75, and 100 weeks. Renal cortices, peritoneal macrophages, thymocytes, and splenocytes were isolated. DNA was isolated and run on agarose gel electrophoresis. Apoptosis of renal cells was evaluated by the TUNEL method and transmission electron microscopy. RNA was isolated from renal cortices and probed with specific cDNA probes for genes associated with active cell death, such as SGP-2, cathepsin-B, and tissue transglutaminase. Mesangial cells (MC) derived from younger and older rats were examined for the occurrence of apoptosis. The effect of estradiol and testosterone was studied on mesangial cell apoptosis.


RESULTS
At 2 weeks, peritoneal macrophages, thymocytes, and splenocytes showed no DNA fragmentation. Apoptosis of macrophages, splenocytes, and thymocytes increased with age in the males as well as females. Mesangial cells derived from aged rats showed a greater percentage of apoptosis when compared to MC derived from younger rats. Estradiol and testosterone directly affect mesangial cell apoptosis. Renal cortices of male rats showed enhanced mRNA expression of SGP-2 and tissue transglutaminase with aging; whereas expression of cathepsin-B peaked at 30 weeks in both male and female rats.


CONCLUSIONS
Age and sex modulate renal cortical mRNA expression of genes associated with active cell death. Age and sex also modulate apoptosis of macrophages, splenocytes, and thymocytes.
Singhal
P C
PC
Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, NY 11040, USA.
Reddy
K
K
Franki
N
N
Sanwal
V
V
Kapasi
A
A
Gibbons
N
N
Mattana
J
J
Valderrama
E
E
D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D051152:Clusterin; D003169:Complement Inactivator Proteins / Q000378:metabolism*; D004247:DNA / Q000032:analysis; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005920:Glomerular Mesangium / Q000187:drug effects / Q000648:ultrastructure; D006023:Glycoproteins / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000502:physiology*; D008297:Male; D018832:Molecular Chaperones; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013154:Spleen / Q000502:physiology*; D013739:Testosterone / Q000494:pharmacology; D013950:Thymus Gland / Q000502:physiology*; D011503:Transglutaminases / Q000378:metabolism*
D051152:Clusterin; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D013739:Testosterone; D004958:Estradiol; D004247:DNA; D011503:Transglutaminases