Leucine depletion extends the lifespans of leucine-auxotrophic fission yeast by inducing Ecl1 family genes via the transcription factor Fil1.

Many studies show that lifespans of various model organisms can be extended by limiting the quantities of nutrients that are necessary for proliferation. In Schizosaccharomyces pombe, the Ecl1 family genes have been associated with lifespan control and are necessary for cell responses to nutrient depletion, but their functions and mechanisms of action remain uncharacterized. Herein, we show that leucine depletion extends the chronological lifespan (CLS) of leucine-auxotrophic cells. Furthermore, depletion of leucine extended CLS and caused cell miniaturization and cell cycle arrest at the G1 phase, and all of these processes depended on Ecl1 family genes. Although depletion of leucine raises the expression of ecl1+ by about 100-fold in leucine-auxotrophic cells, these conditions did not affect ecl1+ expression in leucine-auxotrophic fil1 mutants that were isolated in deletion set screens using 79 mutants disrupting a transcription factor. Fil1 is a GATA-type zinc finger transcription factor that reportedly binds directly to the upstream regions of ecl1+ and ecl2+. Accordingly, we suggest that Ecl1 family genes are induced in response to environmental stresses, such as oxidative stress and heat stress, or by nutritional depletion of nitrogen or sulfur sources or the amino acid leucine. We also propose that these genes play important roles in the maintenance of cell survival until conditions that favor proliferation are restored.

Adiponectin and visceral fat associate with cardiovascular risk factors.

OBJECTIVE: To examine the combined effect of CT-measured visceral fat area (VFA) and adiponectin level against the clustering of metabolic risk factors. DESIGN AND METHODS: The subjects were 6,996 Japanese. The subjects were divided according to the combinations of VFA and adiponectin level quartiles and the odds ratio for multiple risk factors of metabolic syndrome were calculated (adjusted for age and lifestyle factors using logistic regression analyses). Group with the lowest VFA and the highest adiponectin level was used as a reference. The correlation between adiponectin level and each metabolic risk factor was evaluated. RESULTS: The strongest correlation was observed between adiponectin level and high-density lipoprotein cholesterol levels (r = 0.369 and 0.439 for men and women). Both VFA and adiponectin level were independently associated with the clustering of metabolic risk factors (interaction P = 0.58 and 0.11 for men and women). The odds ratio for the clustering of metabolic risk factors in the group with the highest VFA and the lowest adiponectin level, compared with the group with the lowest VFA and the highest adiponectin level, was 12.7 (9.7-16.6) for men and 13.5 (6.0-30.2) for women. CONCLUSION: The ability to detect metabolic syndrome could be improved by examining adiponectin level in conjunction with VFA.