The aging biological clock in Neurospora crassa

The biological clock affects aging through ras‐1 ( bd ) and lag‐1 , and these two longevity genes together affect a clock phenotype and the clock oscillator in Neurospora crassa . Using an automated cell‐counting technique for measuring conidial longevity, we show that the clock‐associated genes lag‐1 and ras‐1 ( bd ) are true chronological longevity genes. For example, wild type ( WT ) has an estimated median life span of 24 days, while the double mutant lag‐1, ras‐1 ( bd ) has an estimated median life span of 120 days for macroconidia. We establish the biochemical function of lag‐1 by complementing LAG 1 and LAC 1 in Saccharomyces cerevisiae with lag‐1 in N. crassa . Longevity genes can affect the clock as well in that, the double mutant lag‐1 , ras‐1 ( bd ) can stop the circadian rhythm in asexual reproduction ( i.e ., banding in race tubes) and lengthen the period of the frequency oscillator to 41 h. In contrast to the ras‐1 ( bd), lag‐1 effects on chronological longevity, we find that this double mutant undergoes replicative senescence ( i.e ., the loss of replication function with time), unlike WT or the single mutants, lag‐1 and ras‐1 ( bd ). These results support the hypothesis that sphingolipid metabolism links aging and the biological clock through a common stress response