Dopaminergenic Neurons Regulate Longevity in Flies

An interesting commentary here notes the extended life span in flies that results from the upregulation of the Mask gene in dopaminergenic neurons only. This is accompanied by extended reproductive life span as well, indicating an overall improvement in health along with extended life. In short-lived species there are many examples of this sort of single gene alteration that results in overall improvement, demonstrating that the processes of evolution do not optimize for life span. Should we expect to find analogous single gene alterations in humans? That question is complicated by the fact that long-lived species such as our own exhibit life spans that are much less plastic in response to metabolic and environmental factors when compared to the life spans of short-lived species. Mice can live 40% longer in response to calorie restriction, 70% longer in response to growth hormone receptor knockout, but in humans neither of those states appears to result in more than a few years gained.

Dopaminergic neurons are critical modulators for essential brain functions such as learning and memory, reward and addiction, motor control, and metabolism. My recent work identified a novel function of dopaminergic neurons in regulating aging and longevity in flies. I demonstrated that overexpressing the putative scaffolding protein Mask in small subsets of dopaminergic neurons significantly extends the lifespan in flies. Interestingly, the prolonged lifespan of the Mask-overexpressing flies is accompanied by sustained reproductive activities, contradicting the long-acknowledged inverse relation between reproduction and longevity.

This prevalent negative correlation between reproduction and longevity has been explained by the disposability theory that posits a competing allocation of energy between reproduction and somatic maintenance. However, my work, together with a few other findings in flies, suggested that extension of both lifespan and reproduction can be induced simultaneously by a variety of specific genetic manipulations. Moreover, such a co-extension also occurs in nature - the reproductive females of eusocial insects acquire physiological transformations that enable the expansion of both their reproduction capacity and lifespan.

It seems that a common mechanism may exist to actively induce adaptations to cope with the reproductive demands of the animals, which also at the same time intervenes the aging process and extends the lifespan. Inspired by this notion, I propose a reproduction-centered theory that explains the seemingly contradictory relationships of reproduction and longevity. The success of reproduction is essential for the survival of the species. From such a reproduction-centered perspective, the maintenance of the somatic tissues is not just critical for the survival of individuals but is, more importantly, essential for the fulfillment of reproduction. Therefore, I postulate that somatic tissues possess the ability to adapt to, instead of competing with, the animal's reproduction states and that such adaptations can consequentially impact aging and longevity.


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