Think about a cell in your body which will not die but will not divide. It persistently releases a noxious combination of inflammatory substances. This is a senescent cell. The hunt was easy, find and kill these biological zombies over the years. But what would happen in case the actual finding is not on killing them? But what shall we do in case we can agree to a ceasefire?
We can discuss this drastic change.
The Old War on Zombies
The discovery that there is an accumulation of these cells with age was the first significant finding. They damage tissues. In 2011, scientists at Mayo clinic conducted a breakthrough discovery. By clearing them out of mice, this increased their healthy lifespan significantly. The competition on senolytics started. Such drugs as the combination of dasatinib and quercetin were snipers. Their mission? Eliminate.
But a problem emerged. It is impossible to carpet-bomb your biology. The aging cell is not necessarily the villain, as it is observed by Dr. Birgit Schilling of the Buck Institute. She demonstrates through research that everything depends on context. In other cases, the cells are useful in the healing of wounds. The crude method of elimination demonstrated its limitation during the initial experiments on human beings to treat arthritis.
We needed a smarter strategy.
Listening to the Static
It is listening that brought the real breakthrough. It dawned on scientists that it is the SASP that is the real threat, the Senescence-Associated Secretory Phenotype. Imagine that it is an evil broadcast signal. This inflammatory scream kills its neighbors. It transforms the issue locally to a system crisis of chronic inflammaging.
This was a discovery that revolutionized the game.
The new goal? Don’t kill the broadcaster. Jam its signal. Schilling says that we are learning the particular language of this decay. Her group applies the highly developed proteomics to decipher the specific chemical vocabulary of the SASP. Every disease could possess its dialect. This nuance is everything.
The New Medicine: Signal Jammers
Enter “senomorphics.” These aren’t hitmen. They’re diplomats. They do not kill the senescence cell. Rather they drown its poisonous talk. This power is exhibited by existing drugs. As an example, the SASP seems to be dimmed by metformin, which is a common medication used to treat diabetes. It is currently being tested in the massive TAME test on aging itself.
Take the example of the discovery of a peptide known as FOXO4-DRI.
FOXO4-DRI triggers cell death. It doesn’t confuse the zombie. It doesn’t inhibit a certain internal dialogue retaining the cell in its inflammatory form. The result? The cell enters into a silent and normal lifecycle or apoptosis without a destructive burst of signals. It’s a targeted mute button. This is a more exquisite finding in the discipline.
A Real-World Test: The Lungs
Let’s make this concrete. Examine Idiopathic Pulmonary Fibrosis (IPF). It is a ruthless, deadly bronchiolar scarring illness. The lungs of IPF patients are discovered to be filled with senescence cells. Their unremitting SASP is the burning of gasoline on the fibrosis fire.
Clinical preclinical activity is in progress.
The Mayo Clinic conducted a pilot study of the senolytic combo (D+Q) on IPF patients. The preliminary results were positive, and they indicated viability and signs of better physical performance. It’s a direct test. Will it be possible to alter the trajectory of a fatal age-associated condition by the means of modulating these cells? This practical case is the demonstration-of-concept the field is in dire need of.
Outside the Hype: A Personal Opinion
This is what I think following an interview with six biogerontologists. The supplement-business has already jumped in. You will find senolytic activator blended online. Because the process of clinical discovery is systematic, this is untimely and hazardous. This is not a so-called anti-aging pill that you can purchase next to the vitamins.
We are referring to the future prescription medicine.
It will depend on certain diseases such as osteoarthritis, Alzheimer, or the rigidity of the blood vessels. The vaccination will be occasional- say a couple of times a year- to rid the body of old zombies without disrupting it long term. The identification of accurate biomarkers will inform the physicians whose treatment to start when.
The Ethical Horizon
It is a science that puts difficult questions. Who then will have them first in case we come up with these therapies? Will they increase health inequalities? According to one of the ethicists at a recent longevity conference, there is a quote that says, we are great at inventing technologies that society is not prepared to have. It is a good idea to extend healthspan. But it is not a simple one.
This we should maneuver ourselves through.
It is not only a biochemical discovery. It’s societal. It will be necessary to mould out equal access when the science is still immature. This discussion is critical as the lab work.
Conclusion: Coexistence and not Conquest
So, where does this leave us? It was exciting that we made the first discovery that these cells could be cleared. However, the more important, more revealing finding is that senescence is life, which we need to control, not only to destroy.
My strong conclusion?
Longevity medicine is not a war of the future. It is an advanced communication with our biologicalness. The goal is balance. To permit the healthy functions of senescence and to hush its horrifying shrieks. The following decade will not be the decade of the magic bullet. It will concern learning to tune the signal. That is the final, and the greatest, discovery of man.