Researchers have found that antibiotic minocycline can increase the lifespan of aged roundworms by preventing the build-up of proteins, revealing a protective mechanism that could be used to help prevent age-related neurodegenerative diseases in humans.
Protein aggregation has been known to cause several progressive age-related brain diseases, including amyotrophic lateral sclerosis, Alzheimer's, Parkinson's and prion disease.
The study, led by a team from the Scripps Research in the US, showed 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.
We have identified minocycline as a drug that can extend lifespan and improve protein balance in already-ageing worms. Our study reveals how minocycline prevents protein aggregation and lays the foundation for drug-development efforts aimed at optimising this already-approved drug for a range of neurodegenerative diseases.Michael Petrascheck, Associate Professor at the Scripps Research
For the study, reported in the journal eLife, 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 older worms was minocycline.
To find out why, they treated young and old worms with either water or minocycline and then measured two proteins called a-synuclein and amyloid-ß -- known to build up in Parkinson's and Alzheimer's diseases, respectively.
Regardless of the worms’ age, those treated with minocycline had reduced aggregation of both proteins as they grew older without even the activation of stress responses.
It is because minocycline directly affects the protein-manufacturing machinery of the cell, known as the ribosome. This was true in worms as well as in mouse and human cells, the researchers said.
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