Rapamycin (Rapa) and dietary restriction (DR) have consistently
been shown to increase lifespan. To investigate whether Rapa
and DR affect similar pathways in mice, we compared the effects
of feeding mice ad libitum (AL), Rapa, DR, or a combination of
Rapa and DR (Rapa + DR) on the transcriptome and metabolome
of the liver. The principal component analysis shows that Rapa
and DR are distinct groups. Over 2500 genes are significantly
changed with either Rapa or DR when compared with mice fed
AL; more than 80% are unique to DR or Rapa. A similar
observation was made when genes were grouped into pathways;
two-thirds of the pathways were uniquely changed by DR or
Rapa. The metabolome shows an even greater difference
between Rapa and DR; no metabolites in Rapa-treated mice were
changed significantly from AL mice, whereas 173 metabolites
were changed in the DR mice. Interestingly, the number of genes
significantly changed by Rapa + DR when compared with AL is
twice as large as the number of genes significantly altered by
either DR or Rapa alone. In summary, the global effects of DR or
Rapa on the liver are quite different and a combination of Rapa
and DR results in alterations in a large number of genes and
metabolites that are not significantly changed by either manipulation
alone, suggesting that a combination of DR and Rapa
would be more effective in extending longevity than either
treatment alone.Keywords: metabolome, rapamycin, transcriptome, dietary restrictio
