Decrease in the lgl tumor suppressor dose in Drosophila increases survival and longevity in stress conditions.
Recent studies suggest that downregulation of tumor suppressor genes might not only favor cancer development but also postpone organisms' aging and increase longevity. However, there is lack of population-based studies directly supporting this idea. We studied the lgl lethal alleles which are widespread in natural Drosophila populations. We demonstrate, for the first time, that animals heterozygous on the loss-of-function lgl tumor suppressor gene display a clear pre-adult viability advantage under stressful conditions (high 29 degrees C and low 16 degrees C temperatures). We found also the survival and longevity advantage effect of the lgl loss-of-function in the temperature stress conditions. The main features of this longevity influence are following. First, the lgl-dependent life span increase is sex-dependent; in all experimental combinations males are more sensitive than females of relevant genotypes. Second, the effect is stronger under the life-shortening temperature stress, 29 degrees C, where the hormesis was demonstrated. Third, the favoring effect of reduced dosage of tumor suppressor displays clearly in old but not young animals, delaying aging. Forth, the maternal or epigenetic inheritance of thermotolerance from mother to offspring appears to strengthen the observed longevity effects. One possible explanation of this stress-adaptive effect of reduced tumor suppressor dose might be a better resistance of Drosophila post-mitotic cells to a stress-associated apoptosis at old ages.
Golubovsky
Mikhail D
MD
Center for Demographic Studies, Duke University, 2117 Campus Drive, Box 90408, Durham, NC 27708-0408, USA. mgolub@cds.duke.edu
Weisman
Nataly Y
NY
Arbeev
Konstantin G
KG
Ukraintseva
Svetlana V
SV
Yashin
Anatoly I
AI
D000483:Alleles; D000818:Animals; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D005838:Genotype; D006579:Heterozygote; D008136:Longevity / Q000235:genetics*; D008297:Male; D009154:Mutation; D012737:Sex Factors; D013312:Stress, Physiological / Q000235:genetics; D013696:Temperature; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D029721:Drosophila Proteins; D025521:Tumor Suppressor Proteins; C081435:l(2)gl protein, Drosophila