BIOTECHNOLOGY
AGEING, DAY AND NIGHT
For years, scientific dogma has held that, with the passage of time, our stem cells lose ability to differentiate between day and night cycles. This loss of circadian rhythm, it was believed, promotes ageing. However, two new studies published in August 2017 in the journal Cell have now revealed that this is not the case (G. Solanaz et al, doi:
http://dx.doi. org/10.1016/j.cell.2017.07.035; and S. Sato et al, doi:
http://dx.doi. org/10.1016/j.cell.2017.07.042). Instead, the researchers at
IRB Barcelona and Pompeu Fabre University (PFU) in Spain, and at the University of California, Irvine, report that stem cells continue to show rhythmic activity during ageing, but reprogramme their circadian functions to better cope with stress. To carry out the study, the
researchers compared stem cells from young – three months old – mice with those of aged mice between 18 and 22 months old, in three kinds of tissue, namely skin, muscle and liver, every four hours over one day. ‘Although ageing always involves
circadian reprogramming, an interesting aspect of our results is that such reprogramming is specific and distinct for each type of tissue studied,’ said Pura Munoz-Canoves, ICREA researcher at PFU. ‘This observation implies that although the entire organism is ageing, each tissue goes through this process in a different way. So to address the slowing down of ageing, it will be necessary to study each tissue separately.’ The researchers observed that genetic reprogramming, likely
involving some type of epigenetic mechanism, occurred in response to a variety of stresses: accumulated DNA damage, inflamed tissues and an inefficient cell self-cleaning process (autophagy). These changes promote ‘greater
damage and greater ageing’ because they redirect the stem cells away from their earlier rhythmic functions necessary for tissue protection and maintenance/repair, explained lead researcher Salvador Aznar Benitah, of IRB Barcelona. In another set of experiments, the
researchers gave mice a low calorie diet for six months and compared them with mice on a normal diet. Mice on the low-cal diet conserved
most of the rhythmic functions ‘of their youth’, they reported. ‘Eating less appears to prevent
tissue ageing and therefore prevents stem cells from reprogramming their circadian activities,’ said Aznar Benitah. ‘The low calorie diet greatly contributes to preventing the effects of physiological ageing.’ Although well known to
delay the signs of ageing in mice and primates, the effects of low calorie diets have yet to be wholly replicated in humans. Nevertheless, the researchers suggest their studies could help explain why calorie restriction may slow ageing.
due to a loss of ‘homeostatic regulation of gene regulation’. In other words, the rate of age acceleration is faster or slower at different parts of our lives, and also affects different organs and tissues of the body differently. ‘If you look at a child’s epigenome
it’s beautiful in its organisation, but flash forward 80 years and it’s as chaotic as a messy child’s room. The implication is that, as we develop a
molecular understanding of how this genetic regulation is lost, remarkable things could happen.’ Re-tuning our epigenetic clock
could have dramatic consequences. Slowing down the rate of age acceleration could potentially be a way to combat any number of diseases of ageing all at the same time.
And because such drugs would be used by everyone: ‘We could slash
35%
Extra lifespan of mice whose so-called senescent or no longer dividing cells have been removed, compared with their genetically identical siblings
healthcare budgets and create some of the cheapest drugs in history,’ David enthused. That prospect, however – a bit
like David’s musical career - is still some way off in the future. Until then, the best course of action for a healthy old age appears to be a balanced diet, keeping active and the occasional glass of red wine. That, and steering well clear of any dangerous ex-lovers.
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