Aging is a lifelong process of growing up and growing old. In humans, it represents many changes that accumulate over time including physiological, biological, physical, psychological and social changes. Meanwhile, drugs stack up, regular checkups fill the schedule. Maturing is unavoidable, however, imagine a scenario where it wasn't.

Ever since man stepped off the time-machine, he has been frantically searching for the ‘fountain of youth’, an exercise that continues, to date, to be the favorite pursuit of many.

Cellular senescence was described first by Hayflick and Moorhead back in 1961. Before that people thought that cells could divide indefinitely. For a long time, it was felt that aging processes were driven by things like the thymus or endocrine changes because it was felt that cells were immortal and did not undergo inherent changes with increasing age. Hayflick and Moorhead change that whole landscape dramatically with their 1961 paper showing that human cells have a limited replicative potential whereupon they start losing replication potential and then they eventually have no replicative potential and they either die or they go into a state of cellular senescence.

You and I are just collections of cells. Magnificent and really complicated collections that exist hopefully long enough to reproduce, and when it gets too tough for ourselves to keep these masses of cells together- we die. It happens to the best of us! And also, the worst of us, and also everybody in between. For humans, as we become older and cellular damage begins to accumulate, an increasing number of cells enter into a state known as Senescence. Once they enter this state, they stop doing a number of things that active, living cells do. Things like dividing and creating new cells, repairing and supporting the tissue that they are a part of. They become a detriment. Senescent cells provoke a variety of different types of damage. They produce an array of inflammatory cytokines and chemokines, immune modulators, growth factors and proteases. They can do a lot of damage, they can cause chronic inflammation, they can encourage nearby healthy cells to also become senescent. And in an effort to survive, senescent cells can even cannibalize surrounding cells to utilize their resources to stay, well, not exactly alive but certainly not dead. This is why they are also called "zombie cells".

Now, normally, senescent cells don't accumulate because they are scoured away by the immune system. But as we age, the immune system goes into decline, and more and more senescent cells escape this process and begin to accumulate. Human senescence manifests as a wide range of deteriorative changes. The “Geroscience Hypothesis” posits that common biological mechanisms of aging play important roles in the susceptibility of aged individuals to multiple diseases.

Now, imagine walking into your annual doctor's checkup and walking out feeling 10 years younger, this isn't figurative imagine literally walking out of the checkup as the same health as you were 10 years ago.

Ok, so, what is the secret?

And the answer is Senolytics it’s a drug that selectively kills senescent cells. And how they do that is pretty interesting.

In most cases, we can thank the lovely proteins BCL-W and BCL-XL. These proteins are like those annoying pop-up ads, they come out of nowhere and you just least sitting there, staring at the screen until that 30-second timer is over. These proteins act the same way, except there is no timer, they stay there forever.

BCL-W and BCL-XL act as anti-apoptotic proteins, so basically "anti-death" proteins. They do this by preventing the release of contents in the mitochondria like cytochrome C, which would have then led to caspase activation, which then triggers apoptosis in the cell. These two proteins basically take away that X button when you try clicking off an add.

So, an answer seems obvious, why don't we just inhibit these two proteins? Well, exactly that is what senolytic drug dose. They inhibit BCL-W and BCL-XL by using small interfering RNAs or siRNAs. In another instance, the small molecule ABT-737 is also used, and this molecule is specifically for inducing apoptosis and senescent cells. These senolytics give you that X button effectively killing off the "advertisement", essentially the overexpression of this particular protein family is a key indicator of a senescent cell, which this senolytic can then specifically pick out and eliminate.

Let's turn this discussion to an examination of some of the available senolytics.

The first of these is quercetin. Quercetin is a flavonoid, a natural plant pigment, with antioxidant, antiviral, antimicrobial, and anti-inflammatory properties. Its main sources are citrus fruits, apples, onions, parsley, sage, tea and red wine. But it has poor bioavailability and chemical instability, making it unreliable in senolytic therapy.

Next up, is Dasatinib. It is used in the treatment of chronic myeloid leukemia and acute lymphoblastic leukemia. It's quite toxic. However, it's been shown to be a fairly effective senolytic.

The next senolytic that we are going to talk about is fisetin. Is a flavonoid and is present in strawberries, apples, persimmons, grapes, onions, kiwi and cucumbers. Studies show that fisetin is a very powerful senolytic, especially compared to other flavonoids.

Another compound that has proved to have senolytic qualities is piperlongumine. Is a naturally small molecule derived from the fruits and roots of the long pepper plant. The pepper plant is found mostly in Southeast Asia and Southern India. Piperlongumine appears to be a promising senolytic because it is less toxic and its oral bioavailability is higher compared to other senolytics. But his mechanism of action is still not quietly understood.

The 21st century is certainly one of major change. The first few decades of this century will witness a fundamental change in the face of the population—literally. Nowadays, senolytics are used in the treatment of various conditions and diseases, such as pulmonary fibrosis, diabetes and cardiac dysfunction. Although, many puzzles remain.

As we age, we not only experience significant stressors such as the loss of a spouse and close friends, but the ability of the body to fight infections becomes slower and less effective. Senolytics may enhance healthspan and delay, prevent, or treat multiple chronic diseases, nevertheless, the road is still long, and more studies are needed to understand how they can help us to turn the clock back and make us look and feel 20 years younger.