Pahlavani M A, Vargas D M
Geriatric Research, Education, and Clinical Center, Audie L. Murphy Veterans Hospital, and Department of Physiology, University of Texas Health Science Center, San Antonio 78284, USA.
Proc Soc Exp Biol Med. 2000 Feb;223(2):163-9. doi: 10.1046/j.1525-1373.2000.22322.x.
The signaling cascade mediated by Ras (p21ras) and MAPK (mitogen-activated protein kinase) and calcium/calmodulin regulating enzymes, calcineurin (CaN) and CaMK-IV, are considered to be essential for T-cell growth and function. In the present study, the effect of aging and caloric restriction (CR) on the induction of Ras and MAPK activation by concanavalin A (ConA) was studied. Splenic T cells were isolated from young (4-6 months) and old (22-24 months) rats that had free access to food (control group), and from caloric restricted old (22-24 months) rats that beginning at 6 weeks of age were fed 60%(40% caloric restriction) of the diet consumed by the control rats. We found that the induction of Ras activity in T cells isolated from control old rats was lower (P<0.001) than that in control young rats. However, the levels of Ras activity in T cells isolated from CR old rats were similar to the levels in the age-matched control rats. The induction of MAPK activity in T cells isolated from control old rats and CR old rats was significantly less than in T cells isolated from control young rats, and caloric restriction significantly (P<0.05) reduced the age-related decline in MAPK activation. We also measured the induction of CaN and CaMK-IV activities by ConA in T cells from control young and old and CR old rats. The induction of both CaN and CaMK-IV activity decreased with age. Caloric restriction significantly (P<0.05) reduced the age-related decline in CaN activity, but had no significant effect on CaMK-IV activity. The changes in Ras/MAPK activation and in CaN and CaMK-IV activity with age or with CR were not associated with alterations in their corresponding protein levels. Thus, caloric restriction has a differential effect on the activation of the upstream signaling molecules that are altered with age.
由Ras（p21ras）和丝裂原活化蛋白激酶（MAPK）介导的信号级联反应以及钙/钙调蛋白调节酶钙调神经磷酸酶（CaN）和钙/钙调蛋白依赖性蛋白激酶IV（CaMK-IV），被认为对T细胞的生长和功能至关重要。在本研究中，研究了衰老和热量限制（CR）对伴刀豆球蛋白A（ConA）诱导Ras和MAPK激活的影响。从自由进食的年轻（4 - 6个月）和年老（22 - 24个月）大鼠（对照组）以及从6周龄开始摄入对照大鼠饮食60%（40%热量限制）的热量限制年老（22 - 24个月）大鼠中分离脾T细胞。我们发现，从对照年老大鼠分离的T细胞中Ras活性的诱导低于对照年轻大鼠（P<0.001）。然而，从CR年老大鼠分离的T细胞中Ras活性水平与年龄匹配的对照大鼠中的水平相似。从对照年老大鼠和CR年老大鼠分离的T细胞中MAPK活性的诱导明显低于从对照年轻大鼠分离的T细胞，并且热量限制显著（P<0.05）减少了与年龄相关的MAPK激活下降。我们还测量了ConA在对照年轻和年老以及CR年老大鼠的T细胞中诱导CaN和CaMK-IV活性的情况。CaN和CaMK-IV活性的诱导均随年龄下降。热量限制显著（P<0.05）减少了与年龄相关的CaN活性下降，但对CaMK-IV活性没有显著影响。Ras/MAPK激活以及CaN和CaMK-IV活性随年龄或CR的变化与它们相应蛋白质水平的改变无关。因此，热量限制对随年龄改变的上游信号分子的激活具有不同的影响。
