Severely restricting a rat's daily intake of calories helps prolong its
life. This regimen that works in primates and even yeast. Now Lin et al.
(p. 2126; see the Perspective by Campisi) have recreated this so-called
caloric restriction in yeast and identified some of the genes required for
its effects on longevity. These include the chromatin-silencing gene SIR2
and a gene for an enzyme in the synthesis pathway of the metabolic
intermediate NAD (the oxidized form of nicotinamide adenine dinucleotide).
Because Sir2p is allosterically regulated by NAD, a decreased metabolic
rate included by caloric restriction could cause altered NAD levels and
thus maintain the ability of Sir2p to silence the expression of deleterious
genes (in this case, the expression of ribosomal DNA that can be toxic to
yeast cells). This connection between silencing and prolonged life induced
by caloric restriction suggests that proteins that silence gene expression
may prove to be useful targets for drugs that modulate life-span.