Mechanisms of aging and liver functions.
OBJECTIVE
Morphofunctional studies suggest that the liver, compared with other organs, ages fairly well. Its success is ascribable to its lasting ability to regenerate, even if the potential of the cells to replicate progressively declines with age. The aim of this study was to analyze some aspects of the early phases of liver regeneration, its capacity to mount a stress response, and the inflammatory response in the early stage of an acute injury.


METHODS
Rats aged 2, 6, 12 and 19 months received a single intraperitoneal injection of CCl(4), and morphological, biochemical and molecular evaluations were done 2 and 24 h later.


RESULTS
AST and ALT, starting at age 12 months, were significantly higher than in the younger rats after CCl(4). Histological modifications were already detectable after 2 h in rats aged 12 and 19 months, thereafter becoming more diffuse and marked, whereas they become evident only 24 h after the intoxication in rats aged 2 and 6 months. Albumin, c-fos, c-myc, hepatocyte growth factor, transforming growth factor-alpha and HSP70 mRNA levels decreased 24 h after CCl(4 )starting at age 12 months. Mast cell density was higher in the young rats than the old ones.


CONCLUSIONS
Our results point to: (a) a basically preserved regenerative response of the aged liver, although somehow weaker and slower, with reduced ability to counteract agents inducing cell necrosis; (b) a decrease in the HSP70 response suggesting a reduction in homeostatic capacity, and (c) a lower inflammatory response during aging.
Gagliano
Nicoletta
N
Department of Human Morphology, University of Milan, Milan, Italy.
Grizzi
Fabio
F
Annoni
Giorgio
G
D000367:Age Factors; D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000410:Alanine Transaminase / Q000097:blood; D000418:Albumins / Q000032:analysis; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001707:Biopsy, Needle; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D017228:Hepatocyte Growth Factor / Q000032:analysis; D007150:Immunohistochemistry; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000473:pathology*; D008111:Liver Function Tests; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity
D000418:Albumins; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase