Reduced Expression of Antimicrobial Peptide Genes Partially Determines the Temperature-Lifespan Relationship in Flies

Short-lived species have a much greater plasticity of life span in response to environmental circumstances than is the case for long-lived species such as our own. Among the most important factors are calorie intake and temperature of the surrounding environment. Both produce sweeping changes in metabolism, and are thus challenging to investigate. Nonetheless, researchers here appear to have identified one of the drivers of the relationship between temperature and lifespan in flies, centered around a portion of the innate immune system that may have multiple roles in the regulation of metabolism.

Fruit flies, which are ectothermic animals, can live more than twice as long at 18°C than at 25°C. Even though it has been thought that this enhanced longevity at a lower temperature (18°C) is caused by a change of metabolic rate, the mechanisms that regulate longevity by ambient temperature are poorly understood. Previously, we found that development at 18°C significantly enhances stress resistance of adult flies with more accumulation of nutrients (especially fat) in the body than development at 25°C. This enhanced resistance to stress was similarly observed in both sexes and sustained up to 30 days after hatching of the adult flies indicating that development at a lower temperature, 18°C, significantly enhances the mechanism(s) of stress resistance.

Higher stress resistance and/or fat accumulation are frequently found in long-lived flies such as mutants of the IGF (insulin/insulin-like growth factor) signaling pathway. From tests of representative stress-related genes, we showed that the development at a lower temperature (18°C) downregulates antimicrobial peptide genes, AttA and DptB, of the Immune deficiency (Imd) pathway. The Imd pathway is known to regulate innate immune responses in Drosophila, and the Imd protein activates two downstream branches which are subsequently responsible for the upregulation of stress tolerance and antimicrobial peptide genes.

The roles of the Imd pathway have been well studied in a humoral response against intruders, which is characterized by the secretion of antimicrobial peptides (AMPs) into the hemolymph. However, whether the Imd pathway is involved in a longevity mechanism has not been reported. Using hypomorphic imd and AttC mutant flies, here, we show that the mild downregulation of the Imd pathway has a beneficial effect for stress resistance with higher fat content in the body even when developed at 25°C. The Imd pathway functions for the immune response in the fat body which is involved in the metabolism and storage of fat in adult flies. Surprisingly, our data show that the fat-body-specific downregulation of Imd AMP genes significantly enhances heat resistance and extends lifespan.

In summary, our data indicate that mild downregulation of the Imd pathway increases stress resistance, lifespan, and fat content in adult flies, which mimics the enhanced stress resistance caused by a lower developmental temperature.



I really cannot understand the rejuvenation pontential of such a research. While, as far as I know none lab now works on lipofuscin. I am going to make lipofuscine research and cannot find any lab which can sell me human lipofuscin!

Posted by: Ariel at May 1st, 2018 12:52 PM

@Ariel: Human lipofuscin is probably much like human cross-links - the only certain source is tissue donated to research, and that is in short supply. Other than that, individual groups have to arrange for samples from old individuals, which again is costly.

Posted by: Reason at May 1st, 2018 1:34 PM

@Reason, now Spiegel lab make and sell artificial glucosepane, I have sent him 4 messages where I asked how to buy glucosepane for research, because we need it for molecular spectroscopy, while he did not answer, even though he aware of them. Hovewer, there is published protocol -- I will ask our chemists can they make glucosepane as in Spiegel lab? As for lipofuscin -- there is also protocol for generating lipofuscin, by the way, I do not know chemistry very well. That will be much simpler to buy them in the lab.

Posted by: Ariel at May 1st, 2018 6:44 PM

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