RNA splicing is the step in gene expression at which pieces of a gene are assembled into the final messenger RNA that encodes the resulting protein. A gene consists of intron sequences (omitted) and exon sequences (included). In some cases different combinations are produced normally and result in different proteins arising from the one gene. In other cases, such different combinations are entirely abnormal and should not occur in a healthy cell. With aging, breakages in the splicing process can result in the appearance of these broken proteins, or in changes in the normal balance of several different proteins produced from the same gene.
You might recall that SENISCA was founded to develop therapies based on reducing the age-related dysregulation of splicing that occurs in tissues throughout the body. The principals of that company argue for splicing dysregulation to be included among the hallmarks of aging, with the idea that it can produce much the same sort of disarray in gene expression as results from epigenetic dysregulation. One of the more interesting aspects of this work on correction of splicing is that it can reverse cellular senescence, in vitro. Accumulation of senescent cells is an important aspect of degenerative aging, and there appears to be a fairly deep connection between certain forms of splicing dysregulation and the onset and maintenance of cellular senescence.
Is it a good idea to restore senescent cells, however? Lorna Harris of SENISCA presented on her work at the recent Longevity Leaders World Congress conference, and the first audience question was exactly that. Yes, you can reverse senescence, but senescent cells are senescent for a reason, so is this restoration wise? Isn't it better to take the senolytic approach and destroy all of these errant cells? In answer, Harris explained her position as being that (a) the SENISCA therapeutics are only restoring cell cycle activity in cases of paracrine senescence, cells that are senescent because nearby senescent cells are encouraging them to adopt that state, and (b) the SENISCA therapeutics will not reverse senescence in profoundly damaged cells.
More data is needed to concretely back up that assertion, but it doesn't seem unreasonable. Not all senescent cells are identical in their regulation of the senescent state, and their state depends on cell type and mode of induction of senescence. That is not very controversial, but equally not very well mapped either. Setting aside the sketchy state of knowledge regarding variations between types of senescent cell, one possible reason to avoid reversal of paracrine senescence is the evidence to suggest that the process of becoming senescent produces significant nuclear DNA damage. Thus even undamaged cells may gain potentially problematic mutations when coerced into senescence by the signaling of other senescent cells.
At the end of the day, prospective risks involving cell damage and the prospect of cancer will have to be quantified with at least lengthy animal studies. That will no doubt happen here in the fullness of time, just as it will for many other approaches to treat age-related diseases by targeting hallmarks of aging.