Acetic acid and acidification accelerate chronological and replicative aging in yeast

Comment on: Murakami C, et al. Cell Cycle 2012; 11:3087-96.     

Relationship between Aconitate Hydratase Activity and Citric Acid Productivity in Fluoroacetate-sensitive Mutant Strain of Candida lipolytica

Fluoroacetate-sensitive mutant strains, K–20 and S–22, of Candida lipolytica could not grow or could only slightly grow on agar media containing di- or tricarboxylic acid involved in the TCA-cycle as the sole source of carbon. Relative activities of aconitate hydratase in the cells of the mutant strains, K-20 and S-22, were approximately 1/10 and 1/100, against that of the parent strain, respectively. This facts support the statement that the mutant strains were extremely sensitive to monofiuoroacetate.

The aconitate hydratase activities of these mutant strains and the parent strain corresponded well to the citric to (+)-isocitric acid ratio in the final fermented broths.     

The Fission Yeast php2 Mutant Displays a Lengthened Chronological Lifespan

The Schizosaccharomyces pombe php2 ⁺ gene encodes a subunit of the CCAAT-binding factor complex. We found that disruption of the php2 ⁺ gene extended the chronological lifespan of the fission yeast. Moreover, the lifespan of the Δphp2 mutant was barely extended under calorie restricted (CR) conditions. Many other phenotypes of the Δphp2 mutant resembled those of wild-type cells grown under CR conditions, suggesting that the Δphp2 mutant might undergo CR. The mutant also showed low respiratory activity concomitant with decreased expression of the cyc1 ⁺ and rip1 ⁺ genes, both of which are involved in mitochondrial electron transport. On the basis of a chromatin immunoprecipitation assay, we determined that Php2 binds to a DNA region upstream of cyc1 ⁺ and rip1 ⁺ in S. pombe. Here we discuss the possible mechanisms by which the chronological lifespan of Δphp2 mutant is extended.     

The Lateral Hypothalamic Area: Peculiarities of Aging and the Effect of Chronic Electrical Stimulation on the Lifespan in Rats

Age-related morphological and functional changes in the lateral hypothalamic area (LHA) were studied in experiments on young adult (6-8 months) and old (26-28 months) male Wistar rats. It was found that during aging the neuronal density in the LHA decreased, and significant qualitative destructive and dystrophic changes in the neuronal population developed. The background impulse activity of LHA neuronal units, the mass background electrical activity recorded from this structure, and the Na⁺, K⁺-ATPase activity decreased during aging. In old rats, the rate of LHA self-stimulation was lower, and the range of reinforcing current amplitudes, which provided self-stimulation intensity close to the maximum, was narrower than in adult animals. Chronic electrical LHA stimulation in old rats ensured an increase in the lifespan and maximum life expectancy in these animals. In addition, the lifespan positively correlated with the duration of LHA stimulation. It is concluded that lowering of the functional activity of the LHA neural systems is one of the substantial aspects of the aging process, and activation of this structure in old animals by its chronic electrical stimulation can exert a geroprotective effect.     

Mutations in the RAD27 and SGS1 genes differentially affect the chronological and replicative lifespan of yeast cells growing on glucose and glycerol

The Sgs1 protein from Saccharomyces cerevisiae is a member of the RecQ helicases. Defects in RecQ helicases result in premature aging phenotypes in both yeasts and humans, which appear to be promoted by replicative stress. Yeast rad27 mutants also suffer from premature aging. As the human Rad27p and Sgs1p homologs interact, a similar interaction between the yeast proteins could be important for promoting longevity in S. cerevisiae. We tested the contribution of a potential interaction between Rad27p and Sgs1p to longevity by analyzing lifespan and parameters associated with longevity in rad27 and sgs1 mutants. The carbon source supporting growth also modulated longevity as evaluated by replicative and chronological lifespan measurements. Growth on glycerol promoted chronological lifespan, while maximum replicative lifespan was obtained with glucose-supported growth. In comparison to the individual mutants, the sgs1 rad27 double mutant displayed a shortened replicative lifespan and was also more sensitive to DNA-damaging agents. In addition to promoting replicative lifespan, the activity of Rad27p was critical for achieving full chronological lifespan. The rad27 mutants exhibited increased oxidative stress levels along with an elevated spontaneous mutation rate. Removal of Sgs1p activity additionally increased the oxidative stress and spontaneous mutation rate in rad27 mutants without affecting the chronological lifespan.