A Little Friday Aging Science

Here are a couple of interesting items in aging science for this fine Friday. The first is something of a puzzle in terms of its significance:

The smell of food can affect the lifespan of flies and even partially reverse the life-prolonging effects of dietary restriction, scientists report this week in Science. These findings suggest the beneficial effects of caloric cutbacks on lifespan may not only depend on the decreased presence of food, but also on the decreased perception of it.

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To see if losing the sense of smell could increase lifespan, the researchers used Or83b knockout flies from the lab of Leslie Vosshall at Rockefeller University in New York. (Or83b, unlike the other 62 putative Drosophila odorant receptors, is broadly expressed throughout olfactory tissues.)

Relative to wild-type flies, fully-fed female Or83b-null fruit flies showed a 56 percent increase in median lifespan. In fully-fed males, the effect was smaller than in females, but males without Or83b showed an up to 42 percent increase in lifespan. Flies that were heterozygous for the mutation exhibited intermediate longevity, and expressing a Or83b transgene in mutant flies restored normal lifespan.

Lifespan further increased in Or83b-null flies after dietary restriction, suggesting that odors affect longevity largely, but not exclusively, through a pathway independent of diet.

It's hard to say where this will go; metabolism and its regulation is eternally more complex than anyone would like it to be, even in lower animals. The many years of work ahead to decipher the underlying mechanisms, working up to mice, primates and then people, in ever more costly and long-term studies remind us that it would be nice to be able to produce benefits in healthy life span without having to fully understand the way in which the entire convoluted system hangs together and reacts. In the meanwhile, the results above do not mean you should drop the practice of calorie restriction for your health and longevity just because you are constantly surrounded by the scent of junk food - some things are similar in flies and people, some are not.

In that vein, Chris Patil of Ouroboros points out research that demonstrates the raw power of modern biotechnology in terms of producing metabolic and biochemical data for interpretation:

Li et al. perform a comprehensive analysis of the colon epithelial proteome over the course of aging. The approach is intellectually straightforward with few surprises, but it’s technically sound, and I think it’s important for biogerontologists to appreciate how far proteomic technology has come - the approach used by these authors could be applied to any system of interest, comparing the old and young states and allowing us to learn about the mechanisms of age-related change in our favorite tissues

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In order to understand the peculiarities of aging cells’ behavior, we must learn not only about their gene expression and proteome but also the condition in which the macromolecules find themselves at any given point in time.

Cellular biochemistry and its changes across a lifetime are fantastically complex - but it is plausible that we can act to identify significant changes (those which cause the most age-related degeneration) and develop the technology to repair or mitigate the effects of those changes without a full understanding of the entire system. You can repair an engine without having to understand how to build each component part - and a setting up a repair shop requires a fraction of the cost of a manufacturing plant.

To look for viable shortcuts in the face of overwhelming complexity is the path of engineering: scientists seek to understand the entire system, while engineers make the best of each new piece of information. For example, the Strategies for Engineered Negligible Senescence (SENS) form a sober look at the state of knowledge today, concluding that we are far enough ahead in the game to strike out and produce viable rejuvenation biotechnologies within the next few decades. More knowledge of biochemistry and aging will make the task easier, and the final results better, but there is nothing (save a lack of funding and will) stopping the research and development community from working towards significant healthy life extension today.

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