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Longevity Briefs: Is Targeting ‘Zombie Cells’ The Way Forward For Treating Ageing?

Posted on 8 February 2023

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Senescent cells are cells that have stopped dividing and functioning properly. In early life, senescence is a boon – it helps to prevent cancer by limiting the number of times a cell can divide. In later life, however, senescent cells become a major problem. They accumulate faster than the immune system can remove them, and contribute to most diseases of ageing through the release of inflammatory molecules. One promising approach to treating ageing is to use drugs that target senescent cells, either by destroying them, suppressing their activity, or turning them back into normal cells. Such drugs already exist and have been used in humans to treat other diseases.

What did the researchers do: In this article, researchers review what we currently know about the importance of senescence in ageing, and the current state of the human evidence for senescence-targeting drugs.

Senescent cells accumulate with age (left). Senescent cells release a harmful cocktail of molecules known as the SASP (senescence associated secretory phenotype). These cells contribute to reduced organ function and eventually to age-related disease. Senotherapies could remove or restore these cells to normal, thus alleviating or preventing age-related disease.
Targeting senescent cells for a healthier longevity: the roadmap for an era of global aging 

Key takeaway(s) from this research: Senescence is a hallmark of ageing – a common feature of most organisms that age. While it may not be a primary cause of ageing (senescence is ultimately a consequence of other age-related damage), it does contribute to many other hallmarks and fulfils all the criteria for a promising target. Accelerated senescence in animals correlates with accelerated ageing and, more importantly, suppressing senescence delays age-related disease and increases lifespan.

So far, clinical trials in humans have mainly looked at two types of drug: senolytics, which destroy senescent cells, and senomorphics, which make senescent cells behave more like normal cells without killing them. So far, these clinical trials have been pretty promising. The current star of senescence-targeting drugs is the combination of leukaemia drug Dasatinib and plant antioxidant Quercetin. This treatment, known as D+Q, has successfully reduced senescent cell loads and inflammation in diabetic kidney disease and pulmonary fibrosis. More recently, D+Q reduced inflammation, restored blood flow and preserved synapses in the brains of Alzheimer’s patients. There are many other drugs undergoing trials, a list of which can be found in the study.

Despite these victories, these are still early days for senolytics. Animal studies suggest that these drugs can be very effective in preventing or delaying age-related diseases and frailty. Unfortunately, it’s much harder to get approval for a human trial of a preventative treatment than for a curative one, especially if you’re trying to prevent ageing, which is not universally recognised as a disease.

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    Targeting senescent cells for a healthier longevity: the roadmap for an era of global aging:

    Title image by National Cancer Institute, Unsplash

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