Teams of North American collaborators from both industrial research centers (Biotime Inc, Mandala Biosciences LLC and Sierra Sciences LLC) and academic institutes (Ontario Cancer Institute, Burnham Institute for Medical Research and The Scripps Research Institute) have demonstrated successful reversal of the developmental aging of normal human cells. Their findings appear as an ahead-of-print research article entitled 'Spontaneous Reversal of Developmental Aging in Normal Human Cells Following Transcriptional Reprogramming' published Regenerative Medicine.
Human embryonic stem (hES) cells have considerable potential as sources of new therapies for a host of intractable human conditions in which cells and tissues become dysfunctional and need to be replaced. Induced pluripotent stem (iPS) cells are similar to hES cells and derived through reprogramming of somatic cells with various combinations of genes. iPS cell technology has excited the scientific community because it has been demonstrated to be a method of transforming adult human cells back to a state distinctly similar to embryonic stem cells (reversing the process of development) without the use of human embryos. Recent reports have suggested that iPS cells, though very similar to embryonic stem cells in many respects, may not have the normal replicative potential of embryonic stem cells (that is, the iPS cells may be prematurely old), a problem some regard as the Achilles heel of iPS cell technology. However, a new study has recently shed new light on the recent controversy over the aged status of iPS cells.
The telomere hypothesis of cellular aging offers the tantalizing possibility to reset the clock of cellular aging for therapeutic effect. The authors measured the reprogramming of telomere restriction fragment length (TRF) of aged differentiated cells and compared it to that of the hES cell line from which they were originally derived. Using precise genetic modifications of a hES-derived mortal cell strain, the team generated six iPS cell lines, and these were surveyed for telomere length, telomerase activity, and telomere-related gene expression. In addition, they measured the same parameters in widely used hES and iPS cell lines and compared the results to those obtained in the six new isogenic iPS cell lines. Cultures of five out of six lines generally showed telomere shortening to lengths similar to that observed in widely distributed iPS lines. However, one line with relatively high levels of telomerase activity progressively increased TRF length over 60 days of serial culture back to that of the parental hES cell line.
Effectively, reversal of differentiation and cellular aging in this cell population means that aged differentiated cells could become young stem cells capable of regeneration. The authors conclude that, although prematurely aged (shortened) telomeres appear to be a common feature of iPS cells created by current pluripotency protocols, the spontaneous appearance of lines that express sufficient telomerase activity to extend telomere length may allow the reversal of developmental aging in human cells for use in regenerative medicine.
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Man has searched for immortality for a long time, though neither the ancient Pharaohs in what is now Egypt nor Ponce De Leon in what is now Florida nor medieval alchemists found it. Vaziri and colleagues may finally be on the trail of what might be seen as the first real step in prolonging life, at least in the test tube. The possibilities are intriguing but much more work needs to be done. To date, what we have learned about telomerase-length control, combined with starvation diets in rodents, the promise of a laundry-list of antioxidants from green tea, grapes, coffee berry, and just about every tannin-containing plant is intriguing but the science is still lacking. This study, a possible path to a reproducible assay, may make assessment of some anti-aging claims more scientific to the benefit of all.
Anti-aging—does it make old young? Can it make chronic (in our arena “poor healing”) acute? While I doubt I will be discussing this with you 100 years from now, I do see tremendous potential if we can develop this observation into a tool for clinical use. I enthusiastically await the following studies.— Daniel Siegel, MD