In fungi, mitochondrial-nuclear interactions are part of a complex molecular network involved in the control of aging processes. The generation of reactive oxygen species at the mitochondrial respiratory chain plays a major role in this network. Mitochondrial DNA instabilities, which are under the control of nuclear genes, affect the generation of reactive oxygen species and modulate the rate of aging. As mitochondria become dysfunctional, they transduce signals to the nucleus and induce the expression of a set of nuclear genes, a process termed retrograde regulation. Molecular data are emerging which suggest that retrograde regulation is involved in lifespan control.