By flushing out cells worn with age, researchers from the Mayo Clinic have extended the lifespans of mice by as much as 35 per cent. It’s an encouraging finding that could eventually lead to similar therapies in humans.
Ageing is a complex biological process with no single causal factor. One particularly critical contributor of ageing, however, is a process known as cellular senescence (senescence being a fancy word for ageing). After a while, our cells stop dividing properly, leading to a host of age-related problems, including frailty, inflammation, tissue and organ damage, and diseases like pulmonary fibrosis, atherosclerosis, and arthritis.
With this in mind, researchers at the Mayo Clinic found a way to destroy these worn-out cells in normal mice, extending their lifespan by as much as 25 to 35 per cent. Excitingly, this ageing process applies to humans as well, giving hope to potential life-extending therapies. The details of this work can now be found in the latest edition of Nature.
The problem with senescent cells is at least twofold. First, their inability to divide properly means they’re no longer contributing to the growth of healthy tissue. Second, these stressed-out cells pollute the body, damaging healthy cells nearby. The result is chronic inflammation, which is closely linked to frailty and other age-related diseases. Tellingly, the accumulation of abnormal amounts of senescent cells tends to happen where disease occurs, including in our lungs, joints and arteries.
Our immune system clears out senescent cells on a regular basis, but this process becomes less effective over time. What’s less known, however, is if these damaged cells are somehow beneficial to our health. Going into the study, the Mayo Clinic researchers asked themselves two important questions: are these senescent cells important drivers of disease, and if so, can their removal be used as a therapeutic mechanism to treat patients of age-related diseases?
To explore the role of senescent cells in ageing, a team led by Jan van Deursen, Chair of Biochemistry and Molecular Biology at Mayo Clinic, created a mouse model in which these cells could be flushed out. The researchers transplanted a foreign gene into otherwise normal mice, allowing them to remove the worn-out cells with a drug called AP20187. It worked quite well, clearing out about 60 to 70 per cent of senescent cells in middle-aged mice (which for mice is about 12 months). Treatments continued until the mice died of natural causes.
The effect was nothing short of extraordinary: The median lifespan of the treated mice were extended by 25 to 35 per cent. Importantly, the intervention didn’t just extend lifespan, it extended healthy lifespan — and without any observable side-effects. Observations of the treated mice revealed delays in tumour formation and preserved tissue and organ function, including reduced inflammation in fat, muscle and kidney tissue.
This research strongly suggests that the accumulation of senescent cells is largely a bad thing; not only do they shorten life, they shorten the healthy parts of our lives. The study also bolsters the theory that cellular senescence is a mechanism that contributes to cancer and the proliferation of tumours. As the research shows, treated mice displayed a decreased disposition towards cancer. The treated mice still developed tumours associated with ageing, but the rate of growth decreased, and they died of these tumours much later.
Looking ahead, the researchers are hoping to apply these findings to the development of life-extending therapies in humans. And they’re not kidding; van Deursen and study co-author Darren Baker have licensed patents to develop such drugs for a company that van Deursen co-founded.
Importantly, this study was done on mice, and humans are obviously not mice. It’s unlikely that a similar intervention in humans would extend our lives by a whopping 35 per cent (which would raise human life expectancy to around 115 to 120 years). But it could very possibly extend human lifespan a bit. And importantly, it would likely stave off age-related diseases and extend the healthy phase of our lives.
Top image: Jan van Deursen