Ar. Heydari et al., EFFECT OF CALORIC RESTRICTION ON THE EXPRESSION OF HEAT-SHOCK PROTEIN-70 AND THE ACTIVATION OF HEAT-SHOCK TRANSCRIPTION FACTOR-1, Developmental genetics, 18(2), 1996, pp. 114-124
The regulation of heat shock protein 70 (hsp70) expression is an excel
lent example of a cellular mechanism that has evolved to protect all l
iving organisms from various types of physiological stresses; therefor
e, the reported age-related alterations in the ability of cells to exp
ress hsp70 in response to stress could seriously compromise the abilit
y of a senescent organism in respond to changes in its environment. Be
cause caloric restriction (CR) is the only experimental manipulation k
nown to retard aging and increase the survival of rodents, it was of i
nterest to analyze the effect of CR on the age-related alteration in t
he induction of hsp70 expression in rat hepatocytes. The effect of CR
on the nuclear transcription of hsp70 gene in rat hepatocytes in respo
nse to various levels of heat shock was determined, and it was found t
hat the age-related decline in the transcription of hsp70 at all tempe
ratures studied was reversed by CR. Because the heat shock transcripti
on factor (HSF) mediates the heat-induced transcription of hsp70, the
effect of CR on the induction of HSF binding activity by heat shock wa
s studied and found to arise from HSF1, which has been shown to be inv
olved in the induction of HSF binding activity in other cell types. Th
e age-related decrease in the induction of HSF1 binding activity in ra
t hepatocytes was reversed by CR, and did not appear to be due to an a
ccumulation of inhibitory molecules with age. Interestingly, the level
of HSF1 protein was significantly higher in hepatocytes isolated from
old rats fed ad libitum compared to hepatocytes obtained from rats fe
d the CR diet even though the levels of HSF1 binding activity were low
er for hepatocytes isolated from the old rats fed ad libitum. The leve
ls of the mRNA transcript for HSF1 was not significantly altered by ag
e or CR. Thus, the changes in HSF1 binding activity with age and CR do
not arise from changes in the level of HSF1 protein available for act
ivation. (C) 1996 Wiley-Liss, Inc.