The aging biological clock in Neurospora crassa

• Published in: Ecology and evolution 2014-09, Vol.4 (17), p.3494-3507
• Main Authors: Case, Mary E., Griffith, James, Dong, Wubei, Tigner, Ira L., Gaines, Kimberly, Jiang, James C., Jazwinski, S. Michal, Arnold, Jonathan
• Format: Article
• Language: English
• Subjects: Aging; Asexual reproduction; Binding sites; biological clock; Biological clocks; Cellular stress response; Circadian rhythms; Experiments; Genes; lag‐1; Life span; Lipid metabolism; Lipids; Longevity; Metabolism; Metabolites; Mitochondrial DNA; Mutants; Neurospora; Neurospora crassa; Original Research; Phenotypes; Proteins; ras‐1; Saccharomyces cerevisiae; Senescence; Stress response; Tubes
• ISSN: 2045-7758; 2045-7758
• DOI: 10.1002/ece3.1202

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 LAG1 and LAC1 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 We establish a mechanistic link between aging and the biological clock through lipid metabolism. The hypothesis is that lipid metabolism provides a shared mechanism to deal with stress in aging and stresses from living in a periodic environment, and we also identify two new genes that affect the clock mechanism. This link of aging and the clock is relevant to understanding diapause in insects, Sundowner's Syndrome in the elderly, how the biological clock functions, and the evolution of circadian rhythms.