Live Fast, Die Later?

A study in roundworms has shown that speed of movement could be a useful predictor of longevity.

AsianScientist (Nov. 30, 2015) – Scientists at South Korea’s Institute for Basic Science have found that the speed at which roundworms move can predict their lifespan and be used to assess their health. The research, reported in Nature Communications, included the discovery of a regulatory mechanism that can extend a worms ‘healthspan,’ or the period in which an organism is at its optimal health.

In previous experiments using several types of mutated Caenorhabditis elegans roundworms (C. elegans), researchers were able to significantly extend the worm’s lifespan. The lengthened life that the worms experienced was not necessarily a good one, as many of the mutated varieties were less healthy than wild-type worms, especially during the segment of life that was extended beyond normal.

Focusing on ‘healthspan’ instead of longer life, the scientists, led by Coleen Murphy, a professor at Princeton University, created their own health assessment for C. elegans. The scientists recorded the maximum velocity (MV) of wild-type C. elegans worms during timed 30 second sessions for a life time.

In the experiment, the worms all showed a decrease in MV from day six and onwards, just as human movement ability declines in later life. Additionally, they found that at day nine (midlife), the median lifespan of worms in the high MV group (23 ± 3.2 days) was 35.3 percent longer than that of the worms in the low MV group (17 ± 3.6 days). The researchers concluded that MV of wild-type worms at day nine of adulthood is a reliable predictor of longevity.

Another factor they observed was the state of C. elegans mitochondria. Elderly humans have weaker muscles and less strength, resulting from mitochondrial defects which occur later in life. Similarly, C. elegans with lower MV exhibit defects by midlife but there are far fewer defects in worms with higher MV at the same age.

These observations indicate that MV correlates with mitochondrial health expression, suggesting that MV can be a reliable indicator of the actual physical state. The findings show that MV of C. elegans is a reliable indicator of age-related physical decline, accurately reports movement ability and if measured in mid-adulthood, is predictive of future longevity.

What sets this research apart from previous studies is that the scientists discovered a genetic regulator that can lengthen good quality life, daf-2. The daf-2 mutation affects the insulin/IGF-1 signaling (IIS) pathway, which in turn has a direct effect on longevity through its control of the metabolism of nutrients and enhances many physiological functions with age.

Tests with daf-2 mutants showed that they had a higher MV than wild-type worms with age, especially at day ten and after. Even after all the wild-type worms had died at day 26 of adulthood, the daf-2 mutants still maintained on average 36 percent of MV. The researchers showed that daf-2(e1370) mutation extends both lifespan and healthspan, without proportionally extending the unhealthy part of life.

However, the group’s findings contradict a previous study which concluded that daf-2(e1370) IIS mutants are less healthy than wild-type animals, disproportionately extending their ‘unhealthy’ lifetime.

As part of their efforts to explain the discrepancies with the previous research, the research groups recorded movement of daf-2 mutants across an unseeded surface, unlike the previous research that used the seeded plates full of food.

The scientists found that daf-2 mutants have an inherently higher preference for food than exploration, presumably because its high levels of the odr-10 odor receptor caused daf-2 mutants to prefer food over exploration, slowing its movement on bacteria.

“Because this type of movement is not limited by ability, but rather by preference, it may be difficult to draw conclusions regarding healthspan from on-food motility assays,” explains corresponding author and IBS director of the Center for Plant Aging Research Hong Gil Nam.

From these results the researchers concluded that the only way to accurately measure worm motility is to conduct the trials on a bacteria-free surface, so the worms didn’t get preoccupied by their ingrained food-seeking behavior.

“Our analysis takes into account the length of time an individual can expect to live, and how healthy that individual can expect to be with age,” says Hong.

The article can be found at: Hahm et al. (2015) C. Elegans Maximum Velocity Correlates with Healthspan and is Maintained in Worms with an Insulin Receptor Mutation.


Source: Institute for Basic Science.
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