Does anybody know works where two or more circadian genes were overexpressed multiplexly and lifespan of a model was observed? Probably somebody knows groups solving the problem of combined overexpression for life extension, I would be grateful to recieve any information.
Dear Ilya! Your question is a little difficult. Please use some references from two papers in the attachment to find the answer.
Vladimir
Dear Ilya, to my knowledge overexpression of more than one clock gene has not intentionally been done in mammals (maybe in Neurospora or other genetic clock model systems). However, double knockouts in mammals have been done (Per1/Per2; Cry1/Cry2 etc.) and the animals showed signs of premature aging.
Just a comment: You should be aware of the problem how the overexpression is done, constant (not rhythmic) or by elevated amplitude, but rhythmic. This may yield very different phenotypes?!
Best wishes, Erik
Dear Prof. Maronde,
I am grateful to you for explicit answer and additional comment. The problem of different types of overexpression which you highlighted is a really significant one. In the lab we often discuss it in relation to circadian oscillator and other genes. We tend to agree with Katewa et al. 2016 (Kapahi lab) underlining the increase of rhythms' robustness as a response to conditional non-oscillating overexpression during all lifespan in Drosophila imago.
In our works (drosophila lifespan studies) we use only constructions overexpressing genes of core clock using simple drivers which don't provide oscillatory activity in transcription profiles which results in tiny but valid life extension . This kind of overactivation in our oppinion hypothetically compensates constantly the age-related decrease in circadian gene expression observed by Zou et al. (2000) and improves robustness.
Article Peripheral Circadian Clocks Mediate Dietary Restriction-Depe...
Dear Ilya,
I have not looked at double-over expression but I have looked at single-over expression of several core clock genes in whole body or specific tissues. Based on that, I would say that effect of double-over expression on lifespan could be tricky as the two genes-when taken individually have different effects on lifespan based on the tissues they are over expressed. I also look at effects of diet on lifespan and that adds a new dimension on the lifespan measurements of the animals.
Cheers,
Subhash
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