In Podospora anserina senescence leading to cellular death occurs regularly after prolonged vegetative propagation. However, the life span of this ascomycete may be extended by various means: 1. Mutations in a least 8 morphogenetic genes belonging to 4 linkage groups postpone drastically or even prevent in certain pairwise combinations (e.g. i viv) the onset of senescence. 2. Inhibitors of mt DNA and of mitochondrial protein synthesis show a life prolonging effect when added in low concentrations to the growth medium. 3. A similar effect was found when mycelia were fed exclusively on non repressive carbon sources. Whereas the anti-aging effect of specific mutated genes is rather permanent, the life prolonging action of the inhibitors and carbon sources is restricted and temporary. These substances have no long lasting effect, since after their removal from the medium aging proceeds. Physiological experiments have further shown the existence of three phases in the life span of Podospora anserina. During the juvenile phase aging is prevented by all of these compounds; during the presenescent phase aging is prevented by inhibitors of mt DNA only, and during the senescent phase aging is irreversible. Senescence may be induced in juvenile protoplasts by DNA extracted from senescent mycelia. This, together with the well known fact that senescence is extrachromosomically inherited, points to extrachromosomal DNA as the causative agent of senescence. This kind of DNA may be connected with or perhaps located in the mitochondria. Collectively, the data are consistent in showing that the syndrome of senescence in Podospora anserina is controlled by a chromosomal-extrachromosomal interaction. In this system, extrachromosomal DNA, perhaps a mt DNA, is identical with the infectious principle initiating the decay of the cell, and nuclear genes supervise its expression.