Anti-aging effect of anti-lipolytic drugs
Exp Gerontol. 2004 Jul;39(7):1061-7. Related Articles, Links
Anti-aging effects of anti-lipolytic drugs.
Donati A, Cavallini G, Carresi C, Gori Z, Parentini I, Bergamini E.
Centro di Ricerca Interdipartimentale sull'Invecchiamento, Universita
di Pisa, Via Roma 55, 56126 Pisa, Italy.
Genetic disruption of insulin and insulin-like signaling pathways may
extend lifespan. Hyperinsulinemia and insulin resistance may
accelerate aging. The hypothesis was tested that a once-a-week
life-long inhibition of insulin secretion by the administration of
anti-lipolytic drugs might have anti-aging effects. Groups of
3-month-old male Sprague-Dawley rats were (a) given standard
laboratory food ad libitum (AL); (b) fed AL 6 days and fasted 1 day
every week (FW); (c) fed AL every other day (EOD), (d) fed like FW and
given Acipimox (50 mg/kg b.w.) on the day of fasting (FWA) by the
gastric tube. The AL, FW and EOD groups received saline
intragastrically. Treatment with ACIPIMOX transiently decreased plasma
free fatty acids, glucose and insulin and increased valine plasma
levels, and had no long-term effect on food consumption and body
weight. By age 6, 12 and 24 months subgroups were taken and the
age-related changes in liver dolichol and autophagic proteolysis-which
are correlated with life-expectancy-were measured. Liver dolichol
levels increased and autophagic proteolysis decreased in mature and
older AL rats; EOD and FWA fully counteracted these changes; FW rats
had significant but smaller beneficial effects. It is concluded that
life-long weekly-repeated transient inhibition of insulin secretion by
antilipolytic drugs may have an anti-aging effect, additive to the
anti-aging effect of a milder caloric restriction. Speculation is that
transiently lower plasma insulin levels might stimulate the anti-aging
cell-repair mechanism autophagy, which has longer lasting effects on
cell housekeeping.
although large doses of nicotinic acid do lower LDL and
VDL, it seems to do so by suppressing liver function, which
can be harmful. This seems to be an effect specific to nicotinic
acid which is not shared by the other forms of niacin (i.e it is
not an effect mediated by the coenzyme NAD+ or NADP+)
It is my unproven belief that other forms of niacin, such as
inositol hexanicotinate, which forgo this effect (along with the
flushing associated with the histamine release) are safer and
just as effective as an anti-aging intervention.