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Reducing Levels of Protein Manufacture Slows Measures of Aging in Nematodes

Researchers here demonstrate that an antibiotic slows aging in nematode worms, providing evidence for it to work through a reduction in protein synthesis. Beyond a slowing of aging, one of the consequences of calorie restriction is exactly this lower level of protein synthesis, a feature that also appears in a number of other interventions shown to slow aging to some degree in short-lived species. Protein synthesis takes place in structures called ribosomes, and so one branch of the now quite diverse field of aging research that has grown from the investigation of calorie restriction is involved in attempting to understand how changes to ribosomal function can influence aging. The interesting part of the research noted here is thus more the ribosomes and less the antibiotic. Unfortunately, and as a general rule, attempts to replicate aspects of calorie restriction have a much smaller effect in humans than is the case in short-lived species. No significant form of rejuvenation should be expected to emerge from this sort of research.

Protein aggregation causes several progressive age-related brain diseases, including amyotrophic lateral sclerosis, Alzheimer's, Parkinson's, and prion disease. This study shows that minocycline prevents this build-up even in older animals with age-impaired stress-response pathways. The number of proteins in a cell is balanced by the rate of protein manufacture and disposal, called proteostasis. As we age, proteostasis becomes impaired. "It would be great if there were a way to enhance proteostasis and extend lifespan and health, by treating older people at the first sign of neurodegenerative symptoms or disease markers such as protein build-up. In this study, we investigated whether the antibiotic minocycline can reduce protein aggregation and extend lifespan in animals that already have impaired proteostasis."

The team first tested 21 different molecules known to extend lifespan in young and old Caenorhabditis elegans (C. elegans) worms. They found that all of these molecules prolonged the lives of young worms; however, the only drug that worked on the older worms was the minocycline. To find out why, the researchers treated young and old worms with either water or minocycline and then measured two proteins called α-synuclein and amyloid-β, which are known to build up in Parkinson's and Alzheimer's disease, respectively. Regardless of the worms' age, those treated with minocycline had reduced aggregation of both proteins as they grew older without even without the activation of stress responses.

The team next turned their attention to the mechanism behind this discovery. First, they looked at whether minocycline switches on stress-signalling proteins that are impaired in older worms, but they found the drug actually reduces their activity. Next, they studied whether it turns off the cell's protein-disposal processes, but this was not its mode of action either. When they used a chemical probe to see how minocycline affects the major protein-regulating molecules in the cell, it revealed that minocycline directly affects the protein-manufacturing machinery of the cell, known as the ribosome. This was true in worms, as well as mouse and human cells.

Finally, the team used worms with increased or decreased protein-manufacturing activity and studied how this altered the effect of minocycline on protein levels and lifespan. As predicted, in mutant worms where protein manufacturing was already decreased, they found that a lower dose of minocycline was needed to further reduce protein levels and extend lifespan. In worms where protein manufacturing was increased, the opposite was seen. This suggested that minocycline extends lifespan by controlling the rate of protein manufacturing at the ribosome.

Link: https://elifesciences.org/for-the-press/57d6122a/antibiotic-could-protect-against-neurodegenerative-diseases-during-aging

Comments

Humans, and probably all mammals, have specialized Fibroblast cells that make most proteins that nematodes do not have. So I am skeptical that this is relevant to humans.

Posted by: JohnD at December 3rd, 2018 11:32 AM

Well it is relevant in the sense that messing with the metabolism can reduce the level and damage accumulation or production.

And with lower rate of metabolical activity it is logical to have somewhat lower oxidative stress.

Of course, even slightly reducing the level of protein synthesis could lead to devastating diseases in humans, so this research gives almost no direct yield from rejuvenation POV

Posted by: Cuberat at December 3rd, 2018 12:17 PM

If I recall correctly, the Ukrainian gerontologist, Vladimir Frolkis, already reported similar results in one of his books published in the 1970s, which he attributed to reduced transcription.

Is it possible that low protein diets extend lifespans by the same mechanism?

Posted by: L Pagnucco at December 3rd, 2018 12:23 PM

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