July 31, 2017

expert reaction to study looking at ageing in cells from people with progeria

Researchers publishing in the Journal of the American College of Cardiology investigate ways to make aged cells younger.

Prof. Dorothy Bennett, recent Past President of the International Cell Senescence Association (ICSA), and Head of the Molecular Cell Sciences Research Centre, St George’s, University of London, said:

“The press release accurately reflects that this short paper shows that insertion of a synthetic RNA into cultured fibroblasts from one HGPS patient (patient with progeria, or Hutchinson–Gilford progeria syndrome) has enabled these cells to divide many more times than untreated cells.  This is called ‘extending cell lifespan’, a topic of much research and interest.

“Cell lifespan is the number of divisions that a cell population can go through before proliferation stops irreversibly, called cell senescence.  Cell lifespan in human cells is positively related to average length of the telomeres (protective ends of chromosomes), which shorten at each division in most normal cells.  The authors show here that telomeres in fibroblasts from progeria patients are often shorter than normal, and shorten with patient age relatively quickly.

“However the press release mentions rejuvenating “cells from children [plural] with progeria”.  Now the paper shows data for one patient, and refers to similar findings on fibroblasts from other patients, but these data are not shown.

“The press release also states that cell functions were also normalised.  While again the paper mentions “other evidence of cell rejuvenation”, namely that several molecular properties of senescent cells were reduced in level, the data are not included and it is said that details will be reported elsewhere.

“Something else not mentioned in the paper or the press release is that exactly the same protocol with the same chemically modified RNA has been used before (2015) to extend cell lifespan in culture, in normal human lung fibroblasts and muscle precursor cells.  They refer to the paper (ref. 5) for a technical point, but not for this prior finding.  JP Cooke was also an author on this previous paper.

“The finding is potentially interesting because other research suggests that premature ageing syndromes are often characterised by accelerated telomere shortening and reduced cell lifespans, and that many of the symptoms of the syndromes can be attributed to cell senescence.  Accordingly a therapy allowing transient telomere extension might well extend life for progeria patients, if the therapy could be applied throughout their bodies.

“Unfortunately there is not currently a safe and accepted way of delivering such an RNA therapy.  They refer to possible new developments, but any such developments have yet to be reported.”

Dr Bridget Bax, Reader in Rare Diseases, Molecular & Clinical Sciences Research Institute, St George’s, University of London, said:

“It is important to note that exposure to the RNA telomerase was only effective in cells from those patients with progeria who had abnormally shorter telomeres.  Cells with normal telomere lengths, representing 29% in this study, did not benefit from treatment with RNA telomerase.  This difference in telomere lengths indicates the involvement of other factors in this disease, so this potential therapy may not to be suitable for everyone with progeria.

“However, the findings are very exciting and have the potential to provide the basis of a diagnostic tool for progeria, and further downstream, may lead to the development of therapeutic approaches for progeria.”

* ‘Telomerase mRNA Reverses Senescence in Progeria Cells’ by Yanhui Li et al. published in the Journal of the American College of Cardiology on Monday 31 July 2017.

Declared interests

Prof. Dorothy Bennett: “No conflict of interest.”

Dr Bridget Bax: “I have no interests to declare.”