Telomere dysfunction is linked with genome instability and premature aging. 
Roles for sirtuin proteins at telomeres are thought to promote lifespan in yeast 
and mammals. However, replicative lifespan of the budding yeast Saccharomyces 
cerevisiae shortens upon deletion of Rif1, a protein that limits the recruitment 
of the sirtuin histone deacetylase Sir2 to telomeres. Here we show that Rif1 
maintains replicative lifespan by ultimately stabilizing another age-related 
chromosomal domain harboring the ribosomal DNA (rDNA) repeats. Deletion of Rif1 
increases Sir2 localization to telomeres and the silent mating-type loci, while 
releasing a pool of the histone deacetylase from the intergenic spacer 1 (IGS1) 
of rDNA. This is accompanied by a disruption of IGS1 silent chromatin assembly 
and increases in aberrant recombination within rDNA repeats. Lifespan defects 
linked with Rif1 deletion are abolished if rDNA repeats are forcibly stabilized 
via deletion of the replication fork-blocking protein Fob1. In addition, Sir2 
overexpression prevents Rif1 deletion from disrupting Sir2 at IGS1 and 
shortening lifespan. Moreover, subjecting cells lacking Rif1 to caloric 
restriction increases IGS1 histone deacetylation and lifespan, while uncovering 
novel genetic interactions between RIF1 and SIR2. Our data indicate that Rif1 
maintains lifespan-sustaining levels of Sir2 at rDNA by preventing excessive 
recruitment of the histone deacetylase to telomeric and silent mating-type loci. 
As sirtuin histone deacetylases, such as Sir2 or mammalian SIRT6, each operate 
at multiple age-related loci, we propose that factors limiting the localization 
of sirtuins to certain age-related loci can promote lifespan-sustaining roles of 
these sirtuins elsewhere in the genome.