The confounding role of sensory perception in calorie restriction and ageing research

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My first post to this blog will begin with a thought provoking paper on how the olfactory system fits in to the longevity promoting effects of calorie restriction.

Calorie restriction is the most studied and reliable way to extend secondary and maximal lifespan, tested in many species since the 1930’s up to recently in rhesus monkeys and preliminary human data.

Why the mechanisms of calorie restriction have been so well conserved throughout species is still an enigma; species in natural settings do not tend to die of old age, they do well beforehand.  Reproductive purposes is a popular theory, and evidence supports calorie restriction as an adaptation during periods of nutritional deprivation to extend the reproductive period.  This I will review in more detail in future posts.  With unifying mechanisms still largely elusive, most theories have explored the impact of the energy content itself on physiological changes to a species.

Environmental cues are becoming increasing appreciated for controlling behavior in many fields; it is no surprise that many external factors influence food consumption.  Building evidence explored in this paper suggests that not only the actual consumption, but simply the perception may in fact have physiological consequences on healthspan for the better or worse.

The longevity mediated effect of calorie restriction, concluded by Dr. Pletcher, seems to be partially from a reduced perception of food availability, and partially from the restriction of nutrients themselves.  Other research suggests other factors such as methionine or glycotoxins in a diet may be largely responsible for the effect of calorie restriction on lifespan, which will be reviewed in other posts.  This research complicates the matter further, adding odor as a variable.

Pletcher describes experiments by his lab in Drosophilia showing a fast modulation of lifespan when nutritional environments are changed, suggesting that sensory perception may be an ignored factor.  They studied olfaction because of gene expression data showing odor sensing related genes were altered by both age and nutrient availability.

They then tested if odorants or the lack of from live yeast affected the lifespan of Drosophilia, by allowing one group to see and smell the yeast but not consume it, and another was denied seeing or smelling yeast.  Indeed, the group exposed to the yeast suffered a reduced lifespan, but only when subjected to calorie restriction.  Compared to controls who consumed the yeast, however, they still lived longer.  This seems to suggest that olfaction is partly involved in the longevity promotion of calorie restriction, with another part coming from biological mechanisms, with possible overlap between the two.

Next they knocked out a gene known to be required for normal functioning of the majority of Drosophilia olfactory receptors , Or83b.  Female mutants experienced about a 50% increase in median lifespan in both low and high nutrient conditions, while the males also lived longer but with a lesser increase than the females.  They also noted that the mutants had a normal size and metabolic rate but are resistant to starvation and hyperoxia, and the females increased triglyceride storage, suggesting alterations of other physiological mechanisms by a reduced sensory perception.

Pletcher describes research by Alcedo and Kenyon in C. elegans, selectively targeting specific sensory neurons with laser ablation, showing roles of gustatory and olfactory neurons on lifespan; with some increasing and some decreasing it.  Pletcher and his group are currently testing if specific gene knockouts or overexpressions and claim to have identified certain neuron populations that influence longevity and the pathways in which they affect target tissues.   Their long term goal:

“…to elucidate the network that couples sensory perception to longevity-from signaling inputs and their associated neurocircuits that detect and decode sensory information; to endocrine cells, hormone identity, and transport that relay that information to target tissues; to transcriptional complexes and gene targets; to transcriptional complexes and gene targets that ensure cell, tissue, and organism survival.”

Cool, this will be fun to watch unfold!

This begs the question if calorie restriction in its fullest in humans in a Westernized culture is even possible anymore, with food abundance and sensory overload difficult to avoid.  It also raises interesting possibilities of mechanisms of longevity regulation that may be lost with such a variety of food choices and combinations in a modern world.


Pletcher, S. (2009). The Modulation of Lifespan by Perceptual Systems Annals of the New York Academy of Sciences, 1170 (1), 693-697 DOI: 10.1111/j.1749-6632.2009.04926.x