April 30, 2015

expert reaction to paper on mechanisms of ageing

A paper published in the journal Science has reported changes in the structure of heterochromatin, a tightly packed form of DNA, as a potential cause of human ageing. Building on previous research, the authors used a model of premature ageing and put forward a number of specific protein which may be responsible for the changes.

Dr Tamir Chandra, Research Associate in Epigenetics, Babraham Institute and Wellcome Trust Sanger Institute, said:

“Premature ageing is often attributed to more or less random damage to DNA and the genome. This new study reinforces that the organisation of chromatin (the packaging of DNA in the cell nucleus with proteins) can also lead to accelerated ageing of cells. Basically some of the tighter chromatin packaging (heterochromatin) is lost during ageing and in senescence. Re-establishing heterochromatin could be a tantalizing concept for rejuvenation or to slow the ageing process.

“Importantly, Zhang et al can mimic the cellular ageing phenotype by directly affecting a key enzyme in heterochromatin formation, without the induction of DNA damage. The authors therefore make an important contribution towards our understanding of Werner syndrome and highlight the importance of heterochromatin and the nuclear periphery in cellular ageing. However, it is also important to note that the study is limited to observations on a cellular level, which the authors themselves point out.”

Prof. Ilaria Bellantuono, Professor of Musculoskeletal Ageing, University of Sheffield, said:

“I think the study is well conducted and address an important question in the field of ageing. The study is about mechanisms related to an adult progeria syndrome and it is unclear at this stage what aspects of human physiological ageing this syndrome reproduces. Epigenetic mechanisms are thought to be an important driver of human physiological ageing and the authors includes preliminary data to show that some of the changes observed in the stem cells of Werner syndrome are also present in the stem cells of older people. However, as the authors says, more extensive studies are needed to understand the relevance of these finding to human ageing and to the potential to translate this into interventions to slow down the ageing process. While in future it may be possible to use the knowledge developed to devise new interventions to slow or reverse human ageing, this is far away in time. We need to remember that this study is conducted in a single cell type in vitro whereas ageing is a complex multifactorial process which affects several systems. Moreover, epigenetic changes associated with cellular ageing are likely to regulate other important cellular functions and intervening may interfere with those functions. ”

‘A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging’ by Zhang et al. published in Science on Thursday 30th April. 

Declared interests

Prof. Ilaria Bellantuono is a grant holder of the funding for the MRC/Arthritis Research-UK Centre for Integrated Research into Musculoskeletal Ageing (CIMA) and also receives funding from Horizon 2020 for the COST Action MouseAGE BM1402