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27.01.2019

SLO1 inhibitors: life extension drugs that keep muscles strong when you age

It may be possible to create a drug that protects muscles against decay in the second half of life, while at the same time perhaps also prolonging life. This hope is aroused by an animal study that American and Chinese biologists have published in Science Advances. The researchers experimented with the 1 millimeter-sized nematode Caenorhabditis elegans.

Study
When nematodes enter their final phase of life, they gradually start to lose their muscles and move less. That has everything to do with the breakdown of their neuromuscular junctions: the points in the muscle tissues that make contact with the nerves. The molecule SLO1 inhibits neuromuscular junctions in nematodes, whether they are old or young. And so the researchers wondered whether they could slow down muscle loss due to aging - and maybe even aging itself - by blocking SLO1.

Results
In a first series of experiments the researchers engineered nematodes in which the gene for SLO1 did not work, and the animals had to do without SLOI. When the nematodes were only a few days old, they moved less. Without SLO1 they were apparently less healthy and vital than normal nematodes [WT]. But at a later age, the animals without the SLO1 gene moved more - and also lived longer.

Yeehaw.

In another st of experiments, the researchers gave ordinary nematodes paxillin, a toxic substance from the penicillin fungus that blocks SLO1.

If the nematodes were still young [1-3 days] when the administration started, the product reduced the physical activity of the animals, without making them live longer. But when the nematodes were already in middle age [5-7 days] when the administration started, the animals actually became more physically active and lived longer.

Conclusion
"It's not necessarily ideal to have a longer lifespan without improvements in health or strength", tells research leader Shawn Xu in a press release. [sciencedaily.com January 2, 2019] "But we found that the interventions improved both parameters - these worms are healthier and they live longer."

The next step is research with laboratory animals that are a bit closer to humans, says Xu. "Studying aging in organisms with longer lifespans is a major investment. But now we have identified a molecular target, a potential site and specific timing, which should facilitate further investigation."

Source:
Sci Adv. 2019 Jan 2;5(1):eaau5041.

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