Serum T-kininogen levels increase two to four months before death.
We have reported an accumulation of T-kininogen mRNA in the liver of aging Sprague-Dawley rats. T-kininogen is a cysteine proteinase inhibitor. Since a disruption of the intracellular protein degradation machinery is known to occur during senescence, we wished to further define the role of this protein in the aging process. As a first step, we have measured T-kininogen levels both in serum and within the liver. We have found that serum protein levels are indeed augmented during senescence, although not as dramatically as the mRNA (2.5-fold versus 8.3-fold). Immunocytochemistry, as well as Western blot analysis suggests that this is due to the presence of T-kininogen within hepatic cells in aged rats. Life-long dietary restriction, a known age-prolonging treatment, decreases the overexpression of the protein in 24-month-old rats. Later, diet-restricted animals still show an increased expression from the gene, the effect being delayed but not abolished by dietary manipulation. Interestingly, a longitudinal study indicated the existence of a positive correlation between the time of increase of serum T-kininogen and the time of death of the animal. Serum T-kininogen was found to increase 2.5-4 months before death.
Sierra
F
F
Nestec Ltd. Research Center, Vers-chez-les-Blanc, Lausanne, Switzerland.
Coeytaux
S
S
Juillerat
M
M
Ruffieux
C
C
Gauldie
J
J
Guigoz
Y
Y
D000375:Aging / Q000097:blood*; D000818:Animals; D015153:Blotting, Western; D003643:Death; D004435:Eating; D007150:Immunohistochemistry; D007704:Kininogens / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains
D007704:Kininogens; D012333:RNA, Messenger