Brain Res Mol Brain Res 2003 Mar 17;111(1-2):175-181
How does prolonged caloric restriction ameliorate age-related
impairment of long-term potentiation in the hippocampus?
Okada M, Nakanishi H, Amamoto T, Urae R, Ando S, Yazawa K, Fujiwara M.
Laboratory of Molecular and Cellular Neurogenetics, LTA Medical
Corporation, 810-0064, Fukuoka, Japan
Prolonged dietary restriction has been reported to suppress
age-induced phenomena. In order to investigate how prolonged caloric
restriction reduces age-related deterioration of hippocampal synaptic
transmission, we compared the levels of major hippocampal
polyunsaturated fatty acids, arachidonic acid and docosahexaenoic acid
between 4- and 26-month-old rats. The Ca(2+) responses upon perfusion
of NMDA or 30 mM K(+) between 4- and 26-month-old rats with prolonged
dietary restriction were also compared using the fluorescent probe
Fura-2. A decrease in membrane arachidonic acid is thought to be a
major causal factor in the age-related impairment of long-term
potentiation. Long-term caloric restriction seems to increase
arachidonic acid levels regardless of age. However, there is no
significant difference of hippocampal arachidonic acid levels between
in freely feeding 4- and 26-month-old rats. Similar results were
obtained from the measurement of hippocampal docosahexaenoic acid
levels. Under caloric restriction, the 500 &mgr;M
N-methyl-D-aspartate-induced Ca(2+) response was greatly reduced by
aging, while the 30 mM K(+)-induced Ca(2+) response was not affected.
In our preliminary data, the amplitude of the population spike after
tetanic stimulation did not differ between 4- and 26-month-old rats
under caloric restriction, while 50 &mgr;M of
2-amino-5-phosphonovaleric acid, a N-methyl-D-aspartate antagonist,
markedly inhibited a potentiation of the population spike in
4-month-old rats, but with negligible inhibition in 26-month-old rats.
>From these results, an age-related impairment of hippocampal
excitatory synaptic transmission may not be solely due to the
reduction of membrane arachidonic acid. Caloric restriction might
prevent age-related reduction in hippocampal synaptic transmission by
enhancing non-N-methyl-D-aspartate mechanisms.
PMID: 12654517 [PubMed - as supplied by publisher]
Ongoing CR monkey study update: "In the monkeys...those on
reduced feeding since the study started are dying at a rate
that is about half that of the monkeys receiving a full food
ration." Associated Press: Eating less may extend human life.
August 1, 2002 : http://www.msnbc.com/news/788746.asp?0si=-http://IanGoddard.net/journal.htm
"To lengthen thy life, lessen thy meals." Benjamin Franklin