The ability to reverse fibrosis would turn back some fraction of the progression of age-related failure in heart, kidney, lungs, and other organs. Fibrosis is a form of scarring in tissue that forms in place of functional structures, and appears to caused by a chronic inflammation state of the immune system, as well as by the growing number of senescent cells found in older tissues. Normal regeneration and tissue maintenance is a complicated, coordinated process involving stem cells, transient senescent cells, immune cells, somatic cells in the vicinity, and a whole lot of signaling back and forth. So it is perhaps understandable that lingering senescent cells, altered signaling, and a dysfunctional immune system could cause it to run awry.
Removal of senescent cells reverses fibrosis to some degree in studies where it has been attempted. Senescent cells cause chronic inflammation through the mix of signals they generate, known to include the inflammatory cytokine interleukin 6 (IL-6), among many others. IL-6 and interleukin 11 (IL-11) are known to share many commonalities. The latter is not among the interleukins so far found to be secreted by senescent cells, however. So given this, and that senescent cells are now so strongly tied by evidence to fibrosis, it is somewhat interesting see compelling evidence for IL-11 to be a driver of fibrosis. It suggests that it is simplistic to blame direct signaling from senescent cells for all inflammatory issues: a great deal of secondary signaling and activity is no doubt taking place as well, not to mention other possible independent causes of inflammation in aging.
Researchers have discovered that a critical protein, known as interleukin 11 (IL11) is responsible for fibrosis and causes organ damage. While it is surprising that the importance of IL11 has been overlooked and misunderstood for so long, it has now been very clearly demonstrated by this work. A protein known as transforming growth factor beta 12 (TGFB1) has long been known as the major cause of fibrosis and scarring of body organs, but treatments based on switching off the protein have severe side effects. The scientists discovered that IL11, is even more important than TGFB1 for fibrosis and that IL11 is a much better drug target than TGFB1.
Fibrosis is the formation of excessive connective tissue, causing scarring and failure of bodily organs and the skin. It is a very common cause of cardiovascular and renal disease, where excessive connective tissue destroys the structure and function of the organ with scar tissue. Fibrosis of the heart and kidney eventually leads to heart and kidney failure, thus this breakthrough discovery - that inhibiting IL11 can prevent heart and kidney fibrosis - has the potential to transform the treatment of millions of people around the world.
"The team is at the stage of developing first-in-class therapies to inhibit IL11 and this offers hope to patients with heart and kidney disease. This therapeutic target for fibrotic diseases of the heart, kidney and other organs may be exactly what we need to fill the unmet pressing clinical gap for preventing fibrosis in patients. We are proud to announce that the suite of intellectual property arising from this research has been licensed to a newly launched Singapore-funded biotechnology start-up Enleofen Bio."