Schematic model for epigenetic and genetic regulation of <i>p16</i> repression during CR.

<p>CR-induced SIRT1 activation in human lung fibroblasts can suppress the <i>p16</i>/Rb pathway through its direct deacetylation effects (epigenetic mechanisms) and indirectly provoking Akt/p70S6K1 signaling (genetic mechanisms). CR can also directly affect epigenetic remodeling in the <i>p16</i> promoter which contributes to <i>p16</i> repression. As a result, <i>p16</i> repression leads to aging delay and cellular lifespan extension.