One of the potential side effects of there now being a very sizable amount of funding devoted to realizing therapies based on in vivo partial reprogramming of cells is an increase in the quality of popular press articles about the treatment of aging as a medical condition. We can hope that journalists become a touch more careful and considered when it comes to a field in which billions in funding are now flowing towards research and development. The bar is of course quite low in the matter of journalism and the science of aging, but improvement is always welcome.
The latest exploration into longevity research is 'controlled reprogramming', specifically of our epigenome. The term 'epigenome' is derived from 'epi', the Greek for 'above', and describes chemical changes to our DNA and DNA-associated proteins. These changes are responsible for altering gene expression patterns, but do not affect the underlying DNA sequence. This explains why cells in our body can have distinct properties and functions, despite containing identical genes. Epigenetic changes can also explain ageing (or so it is hoped), hence reversing epigenetic changes may be the key to reversing ageing altogether.
The basis of controlled reprogramming relies on Yamanaka factors - four transcription factors that can be used to remodel the epigenome of a differentiated cell, such as a skin cell, and return it to an undifferentiated state. Ten years after Shinya Yamanaka received the Nobel prize for his discovery of these eponymous factors, a Silicon Valley startup, Altos Labs, has placed a three billion-dollar bet on the ability of three of these factors to reverse ageing.
Will their bet pay off? Author and scientist Andrew Steele remain unconvinced. Whilst Steele does not doubt that we will see anti-ageing treatments in the near future, he is hesitant to name Altos Labs as their source. He described the ten hallmarks of the ageing process, of which epigenetic changes are only one. Other hallmarks include the accumulation of senescent cells and the shortening of telomeres, caps on the end of our chromosomes that are degraded each time a cell divides. The net result of all these hallmarks, including epigenetic modifications, is the manifestation of ageing in the form of cancer, heart disease, wrinkles, memory loss, diabetes, and general decline. The premise that three simple transcription factors, the Yamanaka factors, could prevent all this suffering might just be too good to be true.
There are examples of age-related changes that can't necessarily be reversed by controlled reprogramming. One example is collagen, an extremely long-lived protein that is replaced very slowly, if at all. Collagen and similar proteins form an extracellular matrix that is vital for maintaining the integrity of nearby cells. Rejuvenating these cells without repairing the extracellular matrix would leave cells unsupported, proving a futile effort. "If reprogramming works, it might be that other treatments are needed in combination with it to realise its true potential, and it would be a great shame if we've failed to develop them in the meantime."