On March 23rd, the Cell published a paper bearing the news that scientists seem to have found a new drug capable of halting the ageing process. How much truth lies behind this claim?
Throughout life, every cell of the human body will eventually become a victim of senility. Cells become damaged and fragile, promoting illness as they age. However, researchers have recently discovered a molecule capable of targeting and killing these senescent cells, through the disruption of their chemical balance – an exciting prospect for the field of gerontology.
The approach was not immediately successful. Dr Peter de Keizer – cell biologist at the Erasmus University Medical Centre in Rotterdam – admits: “I got very rebellious, people insisted I was crazy for trying – and for the first three tries, they were right!”. However, following the fourth attempt, researchers started to see light at the end of the tunnel.
They treated ‘old’ mice – some of which were genetically old, others old due to chemotherapy – with this so-called rejuvenation drug. The mice showed an increment in the interval they’d run in a wheel, as well as an improvement in liver function, leading to a more youthful and active appearance overall. However, results weren’t unanimous – characteristics which seem to improve in some mice, did not in others.
I got very rebellious, people insisted I was crazy for trying – and for the first three tries, they were right!
Researchers have previously tried to communicate with the senescent cells of genetically-modified mice. Through genetic modification of plaques within the arteries of the mice, researchers were able to make them live longer. Whilst such modifications cannot be executed in, or readapted for humans, scientists have discovered at least seven molecular complexes (senolytics) which may be capable of disrupting senescent cells.
Trials centred around this idea are currently in development, although the complexes do possess their own inherent weaknesses. Often the basis of drugs for cancer patients, the complexes can damage and destroy healthy cells, causing a number of unpleasant side effects.
Dr de Keizer and his colleagues examined how senescent cells interact with a defensive protein named p53, in hopes of using the protein to suppress senescence. Surprisingly, the scientists discovered that it is in fact a different protein that intervenes in the process, named FOXO4.
To counter these results, the Erasmus University Medical Centre team decided to modify a peptide capable of transporting a snippet of FOXO4. This peptide induced senescent cells to ‘commit suicide’ by preventing FOXO4 and p53 from working together. As such, it was able to stop healthy cells from being killed.
Furthermore, researchers inserted the molecule into mutant mice modified to age hastily (with approximately half the lifespan of a normal rodent). The peptide seemingly reversed the ageing process, significantly increasing their life expectancies. What’s more, the trial was performed a second time using ‘normal’, elderly mice, and the results obtained were similarly promising.
James Kirkland, specialist in diabetes at the Mayo Clinic in Rochester, asserts that “the paper adds a potentially new way to target senescent cells”. Nevertheless, he also sceptically adds that peptides such as de Keizer’s have their own limitations, and that we should not get our hopes up prematurely. For example, administration of the drug is limited by it’s inability to pass through the digestive system unscathed, meaning that methods such as inoculation or inhalation must be used instead.
…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…
Such limitations explain why the researchers are still hesitant regarding the use of this proposed drug. Their ultimate aim, of course, is to be able to safely test the compound on human subjects; however, Dr de Keizer has said that he is not completely comfortable with starting the treatment on elderly subjects just yet. First, he wants to deduce whether the complex can destroy cancer cells – such as those within brain tumour glioblastomas – as they exhibit a number of similarities with senescent cells. If the results obtained are satisfactory, and only then, Dr de Keizer and his colleagues will begin planning a clinical trial that investigates both ageing, and age-related diseases.
Francis Rodier, molecular biologist at the University of Montreal – an impartial third party – states: “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”.
Of course, the use of this peptide requires cautious consideration in terms of safety and viability, and we must be under no illusion that commercial availability is still far within the future. However, the question remains – might this be the future fountain of youth?