A cure for ageing sounds like something right out of a wild science-fiction film like The Substance.
But scientists could now be close to making this a reality.
Researchers from Osaka University, Japan claim to have found a cellular ‘master switch’ which can reverse the process of ageing.
This protein, called AP2A1, could be the key to future treatments that will turn back the body’s biological clock and undo the damage caused by old age.
As our bodies get older, we build up a growing number of old or ‘senescent’ cells which stop dividing and functioning as they should.
These ‘zombie cells’ don’t die but rather continue to grow and pump out inflammatory chemicals which contribute to age-related diseases.
However, the researchers found that they could turn senescent cells back into young, healthy cells simply by reducing the amount of the protein AP2A1.
In theory, that means scientists could remove the cause of age-related diseases like Alzheimer’s or arthritis by reversing the process of senescence at the cellular level.
Scientists say they have discovered a cellular ‘master switch’ which can reverse the body’s natural ageing process (stock image)
The body’s ageing process is incredibly complex and there is no single factor responsible for why we get old.
However, cell senescence is one process which appears to play a significant role in bringing on the negative consequences of getting older.
Professor Richard Faragher, an expert on cell ageing from the University of Brighton who was not involved in the study, says: ‘Normal cells monitor the number of times they have been called on to divide as a cancer prevention mechanism.
‘So, after a variable number of divisions, these cells become senescent which means they activate pathways to ensure they will not divide again.’
Senescent cells also ‘radically change the way in which they behave’ and start to produce inflammatory molecules and enzymes which degrade the surrounding tissue.
‘They essentially become poisonous to the body,’ says Professor Faragher.
This process causes many changes in the cell but one of the most obvious is that the cells grow until they become up to six times the size of a young cell.
As they grow, senescent cells build up thick, scaffold-like ‘stress fibres’ which stretch across the cell and give it additional support.
Although it might sound like something from the science-fiction film The Substance (pictured), researchers say this master switch could be used to make treatments that ‘cure’ ageing by bringing cells back to a youthful state
Lead author Dr Pirawan Chantachotikul at the University of Osaka says: ‘We still don’t understand how these senescent cells can maintain their huge size.
‘One intriguing clue is that stress fibres are much thicker in senescent cells than in young cells, suggesting that proteins within these fibres help support their size.’
Since AP2A1 is involved in the processes which maintain stress fibres, Dr Chantachotikul and her colleagues decided to investigate whether it also had a connection to cell ageing.
Using a process called RNA interference, the researchers created specially engineered pieces of genetic material to inhibit parts of the DNA in human skin cells called fibroblasts.
Essentially, this process turned down the systems which would naturally produce AP2A1 – leading to lower levels building up in the cell.
When the amount of AP2A1 was reduced, the cells returned to their normal size, started to divide again, and showed signs of youthfulness.
On the other hand, when the researchers increased the amount of AP2A1 the cells started to become bigger and grew thicker stress fibres.
Senior study author Dr Shinji Deguchi at the University of Osaka described the results as ‘very intriguing’.
The researchers examined cells from human skin called fibroblasts (illustrated). When the levels of the protein AP2A1 were reduced, the cells left their old or ‘senescent’ state and began to divide again
The researchers found that senescent cells had larger stress fibres (shown in green) which helped them grow to abnormal sizes. Since AP2A1 helps these stress fibres to grow, it also plays a key role in cell senescence
‘Suppressing AP2A1 in older cells reversed senescence and promoted cellular rejuvenation, while AP2A1 overexpression in young cells advanced senescence,’ he said.
Likewise, in cells that had been artificially aged using UV light or drug treatments, the researchers found higher levels of AP2A1 than they would expect for cells of that age.
Those results were also replicated in epithelial cells which line the surface or organs in various parts of the body.
This suggests that AP2A1 might be a universal part of the ageing process, no matter how ageing occurs or where in the body it happens.
These findings raise the fascinating possibility of using treatments which control AP2A1 as a ‘cure’ for ageing.
Although senescent cells are not the sole cause of age-related illness, they play a significant role in causing some of the worst effects of old age.
Professor Faragher explains: ‘The senescent cells are behaving badly because they are signalling to the immune system to come and remove them, but your immune system is also made of cells and its ability to get rid of them declines over time.
‘The bad things these cells do then cause the problems which we perceive as ageing including everything from wrinkles to vascular calcification’ – a buildup of calcium in blood vessel walls that can lead to heart disease and other conditions.
The Office for National Statistics predicts the life expectancy of men born in 2070 in the UK will reach the age of 85 on average, while women will be nearly 88 when they die. However, researchers hope that this could be extended further with a series of new anti-ageing drugs
Professor Faragher says that learning how to remove senescent cells from our bodies could ‘transform health in later life’ by removing the cause of many age-related conditions.
In their paper, published in the journal Cellular Signalling, the researchers write: ‘Given its significant role in modulating senescence progression and rejuvenation, our findings suggest that AP2A1 may serve as a novel senescence marker and a potential therapeutic target for age-related diseases.’
However, scientists caution that a ‘cure’ for ageing is still likely to be a long way off.
‘Reversing senescence is not without risks because many cells become senescent to avoid turning into cancer cells,’ says Professor Faragher.
Likewise, Dr Lazaros Foukas, a scientist researching ageing at University College London who was not involved in the study, told MailOnline: ‘There are no sufficient data to supporting a potential therapeutic effect of interventions targeting AP2A1.
‘This is an ex vivo [outside a living creature] study and there is no animal model data to support a beneficial effect of targeting AP2A1 on organismal ageing.’
Additionally, Dr Foukas points out that this study only looks at how cell senescence affects the structure, or ‘morphology’, of cells.
He maintains that the more important factor for ageing is a process called senescence-associated secretory phenotype (SASP), which this study doesn’t examine.
‘SASP is the key feature linking cell senescence with ageing pathologies and it refers to the secretion of a large set of proinflammatory factors secreted by senescent cells and causing chronic inflammation which is associated with the diseases of ageing,’ says Dr Foukas.
