A specific cell-penetrating peptide (CPP) can effectively and selectively remove senescent cells - leading to a range of health benefits in mice
Senescent cells are one of the hottest targets in regenerative and longevity focused medicine right now, and many teams and companies around the world are now looking at various ways of removing these disruptive old cells. Senescent cell burden rises with age as more cells cease dividing or become damaged in some form, and research has shown that eliminating these cells can protect against conditions like atherosclerosis as well as increase both lifespan and healthspan.
Finding the best way to remove senescent cells
Previous work has revealed that a combination of the natural product Quercetin with the cancer drug Dasatnib is able to remove some senescent cells, but with poor specificity. Another class of drugs called Bcl inhibitors has proven able to target and destroy senescent cells - including the drug ABT-263. These have known side effects and drawbacks however, and researchers have been searching for better, more accurate ways of killing these cells without harming the rest of the body. While gene directed therapies such as liposomal delivery or RNA based therapeutics could conceivably be an effective therapeutic route, finding a more easily applied pharmacological approach may be more cost effective in the short term.
A new peptide
Researchers at the Erasmus University Medical Center in Rotterdam have discovered that a protein called FOXO4 is enriched in certain senescent cells, and is able to block an important protein called p53. p53 plays a central role in causing apoptosis (cell death). If it's blocked by FOXO4, cells are protected from the cell death signalling.
When the team designed a cell penetrating peptide to prevent this detrimental FOXO4-p53 binding, they found it was successfully able to prevent the interaction and facilitate targeted cell death in senescent cells, but not 'healthy' ones.
“It’s definitely a landmark advance in the field. This is the first time that somebody has shown that you can get rid of senescent cells without having any obvious side effects”
When the scientists injected mice with a model of senescence, they found that applying the peptide boosted fitness and stamina, fur density and reversed kidney damage. When they tested it on ordinary elderly mice they saw similar results, with an increased willingness to explore surroundings - a mark of youthful behaviour. The peptide appeared to be highly safe, with minimal side effects. It was also highly selective; eliminating the more problematic senescent cells that were spewing our inflammatory factors. This breakthrough is certainly promising news and may aid in the development of new peptides, it should be noted that peptide delivery would have to be carefully designed as they would not survive an oral delivery route through the stomach and gut.
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