The impacts of aging are so much more than skin-deep. With time, our bodies become more vulnerable to age-related diseases like heart disease, Alzheimer’s and cancer: leading causes of mortality that cause incalculable suffering and take an enormous toll on our families, our healthcare system, and our society. Reducing this suffering is the reason why longevity researchers do what they do – study the science of aging to uncover new therapies that can help people live longer lives in good health.

At the forefront of this research is the development of senotherapeutics, molecules capable of reducing cellular senescence, a central hallmark of aging. As we age, senescent cells begin to accumulate in our bodies. These dead, zombie-like cells have ceased to divide but remain metabolically active, releasing pro-inflammatory chemical signals called senescence-associated secretory phenotypes (SASP) that induce neighboring cells into senescence. Associated with both intrinsic and extrinsic aging, senescence has been linked to the development of a number of age-related diseases. ¹

By targeting senescent cells, senotherapeutics like our OS-01 peptide may have the potential to delay, prevent, or treat age-related diseases. As longevity research progresses, scientists have discovered that not all senotherapeutics work in the same way. In fact, there are two major types of senotherapeutics–senolytics and senomorphics. So what separates these two types of molecules and how they function? Let’s dive deeper into the fascinating world of senotherapeutics – and how our scientists evaluated OS-01 to discover its type.

While both senolytics and senomorphics reduce cellular senescence, they do so in different ways. Senolytics eliminate senescent cells, while senomorphics prevent them from spreading by inhibiting the release of SASP. ²  While the difference might seem nuanced, the two can actually have very different effects. By selectively killing senescent cells, senolytics reduce the overall cell count. Senomorphics, on the other hand, maintain the overall number of cells while reducing the number of senescent cells.

Both senolytics and senomorphics have potential benefits and drawbacks, and their effectiveness and safety depend on the specific drug, the disease being targeted, and the patient population.

Like targeted missiles, senolytics seek out and eliminate senescent cells. This means they may help delay or even reverse age-related conditions. Preclinical and early clinical trials have shown promising results on various age-related diseases including osteoarthritis, atherosclerosis, and lung fibrosis.

When it comes to downsides, senolytics may have the potential to miss their target and harm healthy cells, especially if they’re used for long periods or in combination with other drugs. Some evidence also shows that senolytics may not be effective against all types of senescent cells, which may limit the types of conditions that they can treat. Plus, because they simply kill senescent cells rather than treating the underlying causes of senescence, senolytics may not be a definitive cure for senescence-associated diseases. ³

Because they address the root causes of senescence by targeting multiple pathways, senomorphics may be slightly more versatile than senolytics–meaning they might be able to treat more conditions. Plus, because they don’t kill senescent cells, they come with less risk of inadvertently targeting healthy cells. They’re also considered easier to work with– because they do not need to penetrate cells, senomorphics may be easier to formulate into effective drugs or supplements that people can use.

While senomorphics have a lot of upsides, they also have more complex and less-defined mechanisms of action, which may make it difficult to predict both their effects and potential side effects. And, because they may not be as effective as senolytics in reducing the number of senescent cells, they may show less pronounced benefits. ³

When we discovered that our OS-01 peptide reduced cellular senescence in ex vivo human skin samples, it was important for us to understand exactly how it works. Is it killing senescent cells like a senolytic or suppressing the spread of senescence like a senomorphic?

To find out for sure, we analyzed key SASP markers, IL-6, CXCL1, and CXCL8, in in vitro skin cells and ex vivo human skin samples treated with OS-01. In in vitro skin cells, OS-01 significantly reduced IL-6 and CXCL1. In ex vivo human skin samples, it also reduced CXCL8 and showed a trend towards decreased IL6. This data shows that, because it reduces SASP markers, OS-01 should be considered a senomorphic. This means that OS-01 prevents pre-senescent cells from progressing into late senescence and accumulating within the skin ⁴ (Zonari, et al., 2023). 

This is likely how the OS-01 peptide achieves its visible age-reversal benefits. By preventing the accumulation of senescent cells, OS-01 can support collagen production markers, reduce melanin deposits which cause hyperpigmentation, and boost epidermal thickness*– helping your skin not only look younger, but also behave like younger skin.

*Shown in ex vivo human skin samples

The development of senotherapeutics is still in its nascent stages. While scientists have identified a number of molecules capable of reducing senescence, more research is needed to understand exactly which diseases these molecules are capable of addressing. New breakthroughs are being made every day – keep an eye out for senolytics and senomorphics in the news as longevity researchers uncover more about their therapeutic potential.

• Senotherapeutics are molecules like the OS-01 peptide that are capable of reducing cellular senescence, a central hallmark of aging.
• There are two major types of senotherapeutics: senolytics, which kill senescent cells and senomorphics, which contain the spread of senescent cells by blocking factors that would otherwise induce neighboring cells into senescence
• Both senomorphics and senolytics have potential benefits and drawbacks when compared to one another.
• Because it has been shown to reduce SASP markers rather than killing senescent cells, the OS-01 peptide can be considered a senomorphic.
• This is how OS-01 achieves its primary benefits, including its ability to reduce skin’s biological age (Zonari, et al., 2023).

References:

1. https://www.frontiersin.org/articles/10.3389/
2. https://febs.onlinelibrary.wiley.com/
3. https://www.thelancet.com/journals/lanhl
4. https://www.nature.com/articles/s41514-023-00109-1