GENOTYPE AND AGE INFLUENCE THE EFFECT OF CALORIC RESTRICTION ON MORTALITY
M.J. FORSTER, N. SUMIEN, P. MORRIS, R.S. SOHAL
Department of Pharmacology and Neuroscience,
University of North Texas Health Science Center,
3500 Camp Bowie,
Fort Worth, TX 76107
In mammals, long-term restriction of caloric intake
has been associated with increased longevity and delayed
onset of age-associated pathology. The purpose of the
current study was to determine the influence of genotype
on the relative risk of mortality associated with
long-term caloric restriction versus that associated
with short-term shifts in caloric intake implemented
at different ages. In one study, groups of male C57BL/6,
DBA/2 and B6D2F1 mice were maintained under ad libitum (AL)
or restricted (CR) diets beginning at four months,
and maintained until death. In a companion study, groups
of mice were maintained chronically under AL or CR
until 7, 17, or 22-26 months of age, whereupon half
of each AL and CR group were switched to the opposite
condition for up to 12 weeks. This procedure yielded
four experimental groups (AL-AL, AL-CR, CR-CR and CR-AL),
designated according to long term and short term diet
history, respectively). Long-term caloric restriction
resulted in increased median and maximum lifespan in
C57BL/6 and B6D2F1 mice, but failed to affect either
parameter in the DBA/2 mice. Mortality risk following
short-term changes in caloric intake was also influenced
by genotype and was age-dependent. Increases in caloric
intake failed to affect mortality of chronically
restricted mice (R-A) of any age group, whereas
implementation of caloric restriction in 17- and
24-month old chronically ad libitum fed mice (A-R)
tended to increase mortality. The increase was most
dramatic in DBA/2 mice, but also evident in C57BL/6
and B6D2F1. The current findings indicate that both
genotype and advancing age may confer resistance to
and/or intolerance of the effects of caloric restriction.
Key words:
Caloric Restriction, Genotype, Age
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