Begmanova Mamura, Mit Nata, Amirgaliyeva Anara, Tolebayeva A, Djansugurova Leyla
Institute of General Genetics and Cytology, Almaty, Kazakhstan.
Cent Asian J Glob Health. 2014 Dec 12;3(Suppl):153. doi: 10.5195/cajgh.2014.153. eCollection 2014.
Aging and longevity control are among the greatest problems in biology and medicine. The fruit fly is a nice model organism for longevity investigations because of its biological features. Many genes have their orthologs, similar in other eukaryotes, including human. The role of nitric oxide (NO) in the lifespan has been analyzed.
Virgin flies of dNOS4 transgenic strain were used for the experiment. This strain contains non-functional additional copies of nitric oxide synthase (NOS) gene under heat shock promoter. For promoter activation, transgenic flies on their second day of life were exposed to heat shock (37°C) for an hour. After heat shock, flies were maintained on standard medium temperatures at 25°C, with females separate from males. Two types of control were used: Oregon R wild-type strain and Oregon R strain exposed to heat shock. The average lifespan was evaluated.
It was revealed that the longevity of females was significantly higher than males in each series of experiments ( < 0.05). The survival rate of females and males was similar in the first month of their life, but in the second month the mortality among males was much higher than among females in all series of experiments. The average lifespan of dNOS4 imago was 31 days (34 days for females and 28 days for males), maximum lifespan was 63 days. In controls, the average lifespan of Oregon R flies was 54 days (58 days for females and 50 days for males), and the maximum lifespan was 94 days. The average lifespan of Oregon R flies exposed to heat shock was 45 days (48 days for females and 41 days for males), and the maximum lifespan was 72 days. The difference between average lifespan in all studied groups is statistically significant ( < 0.05).
Thus, NOS-transgene activation results in formation of non-functional dNOS4-transcripts and NO deficiency. In turn, NO deficiency decreases dNOS4 imago lifespan.
衰老和寿命控制是生物学和医学中最重大的问题之一。果蝇因其生物学特性，是用于寿命研究的优良模式生物。许多基因都有其直系同源基因，在包括人类在内的其他真核生物中相似。一氧化氮（NO）在寿命方面的作用已得到分析。
使用dNOS4转基因品系的处女蝇进行实验。该品系在热休克启动子下含有一氧化氮合酶（NOS）基因的无功能额外拷贝。为激活启动子，将出生第二天的转基因果蝇暴露于37°C热休克1小时。热休克后，果蝇饲养在25°C的标准培养基温度下，雌雄分开。使用了两种对照：俄勒冈R野生型品系和暴露于热休克的俄勒冈R品系。评估平均寿命。
结果显示，在每个实验系列中，雌性的寿命显著高于雄性（<0.05）。雌雄果蝇在生命的第一个月存活率相似，但在第二个月，所有实验系列中雄性的死亡率远高于雌性。dNOS4成虫的平均寿命为31天（雌性为34天，雄性为28天），最大寿命为63天。在对照中，俄勒冈R果蝇的平均寿命为54天（雌性为58天，雄性为50天），最大寿命为94天。暴露于热休克的俄勒冈R果蝇的平均寿命为45天（雌性为48天，雄性为41天），最大寿命为72天。所有研究组的平均寿命差异具有统计学意义（<0.05）。
因此，NOS转基因激活导致无功能的dNOS4转录本形成和NO缺乏。反过来，NO缺乏会缩短dNOS4成虫的寿命。
