A Single Gene Modification that Improves Both Mood and Longevity in Mice

A number of genetic modifications that enhance longevity in mice are unambiguously positive: the result is quite literally a measurably better breed of mouse, stronger, with greater endurance, or smarter, or more resilient in some other way. Downsides are minimal or non-existent. Researchers are paying more attention to benefits other than longevity that result from these studies nowadays - there are now so many ways of extending mouse life that announcing a new one won't get you much press unless it has some other novel twist to accompany it.

So here we have a novel twist: a single gene manipulation that improves mood and neural function as well as modestly extending life. Take a look at the abstract or open access PDF paper:

The role of α1-adrenergic receptors (α1ARs) in cognition and mood is controversial, likely due to past use of non-selective agents. α1AAR activation was recently shown to increase neurogenesis, which is linked to cognition and mood.

We studied the effects of chronic α1AAR stimulation using transgenic mice engineered to express a constitutively active mutant (CAM). CAM-α1AAR mice showed enhancements in several behavioral models of learning and memory. ... WT mice treated with the α1AAR-selective agonist, cirazoline, also showed enhanced cognitive functions. In addition, CAM-α1AAR mice exhibited antidepressant and less anxious phenotypes in several behavioral tests when compared to WT. Furthermore, the lifespan of CAM-α1AAR mice was 10 percent longer than that of WT mice.

Our results suggest that chronic α1AAR stimulation improves synaptic plasticity, cognitive function, mood, and longevity. This may afford a potential therapeutic target for counteracting the decline in cognitive function and mood associated with aging and neurological disorders.

Some caution is called for however, as is the case for the results of all studies that don't control for calorie intake. Mice are so very sensitive to calorie restriction that any alteration or treatment that incidentally reduces their calorie intake will extend life - and 10 percent life extension is well within the bounds of that happenstance. If you look at the Wikipedia entry for cirazoline, you'll see:

Cirazoline has also been shown to decrease food intake in rats, purportedly through activation of alpha 1-adrenoceptors

So this is a study that should be repeated with calorie controlled mice.

Still, it remains the case that at what is still the dawn of the age of biotechnology, mice can already be tweaked in more than a score of ways to produce a better species. This raises the question of how true this is for other mammals - such as we humans, for example. Nowhere near as much work, testing, and experimentation has been performed on any other mammal species as has been accomplished with varying breeds of rodents. But we all came to have our own specific biological systems through the same general workings of evolution, and if one mammal species can be improved with a few selective genetic modifications, we might well wonder how true is that of the others:

The question for today is whether there exist as yet undiscovered and comparatively simple mutations in humans that will significantly extend healthy and maximum life spans. How likely is this, given what we know to date? Are potential human longevity mutations worth chasing?

Thanks for blogging about our paper! We didn't track food consumption in the longevity study, which is unfortunate, but there was no difference in body weight between groups. Recently, with long-term cirazoline treatment there was no difference in food consumption (unpublished data). According to some papers in the primary literature, the appetite suppression seems to be a dose-related effect, which we haven't seen at our dose.


Posted by: Katie Collette at September 13th, 2013 2:18 PM

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