Senolytics to Stop Zombie Cells and the SASP Aging Cycle

Reducing senescent cells shows strong tissue rejuvenation potential, which is proposed here as an approach to anti-aging cosmetics and whole body health.
Reducing senescent cells shows strong tissue rejuvenation potential, which is proposed here as an approach to anti-aging cosmetics and whole body health.

Read the full version in the February edition of C&T Magazine

Beauty and appearance play crucial roles in social communication and interaction on both a biological and psychological level, forming our identity and affecting our confidence and happiness. It is therefore not surprising that the current anti-aging market has reached US $65 billion and is estimated to expand to $120 billion by 2030.1

Despite such large numbers, today’s anti-aging solutions do not appear to satisfy consumers, as the latest trend toward well-aging rather than anti-aging seems to demonstrate. Here, senolytic ingredients could provide answers. This article discusses the major why’s and how’s of senolytics and proposes their potential to revolutionize cosmetics and personal care.

The ‘Zombie Cell’ Story

To understand the potential of senolytics, one must first know the story of senescent cells. Often described as zombie cells in some nomenclature, these cells occur due to several inducers: time (e.g., telomeric shorting),2 UV damage (i.e., solar radiation),3 oxidative stress (e.g., mitochondrial deterioration),4 toxins (e.g., pollution/smoke5 and alcohol6) and other causes (e.g., expression of oncogenes7 and obesity8).

All inducers lead to some form of genomic damage in the cell with three general outcomes (from best to worst): 1) the cell goes into apoptosis (self-sacrifice) to avoid the spread of erroneous genomic information to daughter cells; 2) the cell becomes senescent and mitotically inactive to also avoid the spread of erroneous genomic information – e.g., aged human skin can have up to 60% senescent cells;9, 10 and 3) the cell continues to divide and eventually becomes malignant. While the senescence option prevents the worst outcome, it is more of a quick fix that will result in repercussions over time.

A major problem with senescent cells – besides their lack of contribution to “tissue society” – is that they are also harmful to surrounding healthy cells. This is because they release a plethora of harmful factors such as pro-inflammatory mediators, extracellular matrix-damaging molecules, oxidants and more, which are collectively known as the senescence-associated secretory phenotype (SASP).11 From a cosmetics perspective, the SASP turns happy, high-performing and healthy cells of the skin and hair into unhappy and low-performing ones, affecting, for example, collagen/hair pigment production and integrity due to high inflammatory and protease levels. Furthermore, continued exposure to SASP can turn normal cells into senescent ones;12-14 hence, the zombie analogy.

The SASP also influences stem cell pools by inhibiting their proliferative rate,15 which further adds to the detrimental vicious cycle of senescent cells. This generally means the more senescent cells there are in skin, the older the individual’s appearance becomes (e.g., showing wrinkles, sagging, greying and hair loss). As such, the accumulation of senescent cells is a fundamental cause for (skin) aging.

There are three main strategies to address senescent cells and they often are confused with one another, potentially resulting in improper consumer advertisement. The first strategy is the prevention of senescent cells, which includes following a healthy lifestyle that minimizes the inducers of senescence and the use of ingredients that promote cell integrity (e.g., antioxidants, and autophagy and DNA repair agents). The second strategy is the mitigation of harm from senescent cells; i.e., using ingredients that target the SASP factors and prevent their harmful impact. The third strategy is to remove the senescent cells.

From these strategies, the third is the most powerful and, for many, the most relevant. This is because once there are enough senescent cells to notice their effects, the damage has already been done, so prevention is not an option. Mitigation of senescent cells is also not optimal as there are potentially more than 100 SASP factors and these would continually require regulation. This approach carries an additional risk since long-term exposure of SASP is known to promote carcinogenesis,16 so failure to fully inhibit all relevant factors would eventually be catastrophic.

Read the full version in the February edition of C&T Magazine


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