The Fight Against Zombie Cells: Why We Made The Senolytic Series

Want to know the origin of the expression 'happy as a clam'? Part of the answer may be that "animals like the ocean quahog clam exhibit a rare phenomenon known as negligible senescence. This means they don’t seem to show any signs of ageing as they get older, maintaining bodily and reproductive fitness (1).”

Senolytics are the next best thing to achieving negligible senescence in human skin, with a side effect of inducing a state of happiness.

Cellular senescence is one of the primary hallmarks of skin aging. As we age, we accumulate more senescent cells: cells that have stopped dividing but refuse to die. Instead, they collectivize into a band and go marauding. In skincare terms, that band is the secretome, a collection of signaling factors called the senescence-associated secretory phenotype, or SASP. And what a band it is: pro-inflammatory cytokines, chemokines, matrix metalloproteinases, and exosomes, all playing over each other and contributing to epidermal thinning, wrinkles, sagging, hyperpigmentation, and compromised barrier function. Worse, their off-key signaling can lure healthy neighboring cells into becoming zombies, amplifying inflammation into chronic inflammation, aka inflammaging. We call it skinflammaging.

Is there a way to drive these unwanted invaders away from regions where they inflict damage?

The simple answer is yes, but behind the simple yes lies a complex picture involving years of research and lab work. At Marie Veronique, we looked at three things:

1. The specific senescent cell types responsible for skin aging.
2. The skin regions most affected, i.e., the stratum corneum, the epidermis, and the fibroblast/dermal area.
3. And finally, ingredients and delivery systems most likely to succeed in mitigating the zombie effect.
   

Senescent Cell Types

Firstly, not all senescent cells are alike. Some types of senescent cells support repair, while others are associated with specific symptoms of aging.

In skin, p16- and p21-marked senescent cells increase with age, contributing to impaired skin function in different ways and across different regions.

P21

Influences visible signs of aging like wrinkles and sagging. The SASP of p21 dermal fibroblasts is abundant in enzymes called MMPs (matrix metalloproteinases), which signal fibroblasts in the dermis to break down collagen. At the same time, p21 fibroblasts are undergoing a sharp decline in their capacity to synthesize new collagen and elastin fibers. The upshot is a dysergistic effect whose visible results are sagging, deep wrinkling, and loss of elasticity.

And if that wasn’t enough, the SASP of p21-high cells is abundant in proinflammatory cytokines (think IL-6 and IL-8) which seep into adjacent, healthy cells to exert their zombie powers. There goes the neighborhood.

P16

Both age and sun damage cause p16-high cells, particularly the specialized pigment cells called melanocytes, to build up in the epidermis.

P16 is the long-term marker of deep, irreversible cell-cycle arrest. Besides the usual damage, its SASP acts in the skin to stop basal keratinocytes from dividing normally. This vile activity is responsible for the shrinking epidermal layer and resultant thin, crepey skin characteristic of old age.

Let’s also look at p16s and p21s together-

They both accumulate in the epidermis, and recent studies show p21-senescent melanocytes triggering elevated and erratic synthesis of melanin (2). Together, the pro-inflammatory factors in their respective SASPs communicate confusing signals to adjacent cells, and all this chaos shows up eventually as keratoses or age spots, as well as uneven skin tone.

Taken altogether, what we get from p16 and p21 senescent cells are wrinkles, sagging, loss of elasticity, age spots, hyperpigmentation, and thin, crepey skin. Fortunately, we have developed tools.

Senolytics

Senolytics are a special category of senotherapeutics. They target and selectively eliminate senescent cells, while leaving the healthy cells alone. Fisetin, a plant-derived bioflavonoid, is especially powerful when it comes to selectively clearing p21 senescent cells by means of targeting p53/21 and BCL-2 survival pathways.

Very simply, it forces zombie cells to undergo cell death or apoptosis.

Our Senolytic Serum contains encapsulated fisetin, which can penetrate to the fibroblasts where p21 senescent cells are doing their worst damage. The fisetin arrives, delivers the message, and the zombie cells die.

The Senolytic Balm contains fisetin in a matrix of barrier-enhancing ingredients like resveratrol, CoQ10, and Vitamin C ester. This fisetin remains on the skin’s surface to clear p16-high senescent cells that create the paper-thin, fragile skin. In addition, it clears p21s, which also increase at the epidermal level as we age. This aids in mitigating the appearance of age spots and hyperpigmentation caused by p21 senescent melanocytes.

Marie Veronique uses two different versions of fisetin to resolve related skin aging issues.

1. If your concerns are hyperpigmentation, dry, thinning skin, and barrier dysfunction, the balm is a great option.
2. If you are concerned about the more profound effects of aging that come from loss of structural support, deep wrinkles, and sagging, then Senolytic Serum will be a good choice.
   

Balm → epidermal thinning + barrier support

Serum → extracellular matrix (ECM) repair + firming support

When to Use Senolytics

Our Senolytic Series complements existing Marie Veronique active products. By optimizing the cellular environment and reducing inflammatory burden, the formulas enhance skin responsiveness, helping you maximize the efficacy of retinoids and antioxidants in your regimen.

The formulas can be used alongside all Marie Veronique products, with no contraindications. They can be used with retinol or, depending on your preference and regimen, on alternating nights. The Senolytic Series is additive rather than a substitute or alternative to other actives. Like all of our formulas, these products are tools that can be used daily or incorporated throughout the week according to what works best for your skin and routine.

It is, of course, possible to use both. (As we get older, we tend to need more of everything. C’est la vie.)

Here’s a sample nighttime regimen for anyone curious about adding a senolytic to their routine, designed to support the skin’s natural nighttime repair processes and help you wake up with your most plump, glowy skin yet.

1. Pure + E.O. Free Oil Cleanser

2. Balancing HypoTonic

3. Senolytic Serum

4. Multi-Retinol Night Emulsion

5. Senolytic Balm

It’s important to note that our senolytic products are designed for the ongoing maintenance of aging skin, rather than for use during active wound healing. If you're undergoing an invasive procedure, such as microneedling or laser treatments, we recommend setting senolytics aside and focusing on barrier-supportive products to help support the skin's recovery. Once your skin has fully healed, you can return to your senolytic routine.

And while starting early may seem appealing, there's no need to rush into age-related interventions. If you're under 35, prioritize the fundamentals: antioxidants, sun protection, and a healthy skin barrier. Save more targeted longevity actives for when they're appropriate for your skin's needs.

Shop the Senolytic Series at the link below.

Any topic discussed in this article is not intended as medical advice. If you have a medical concern, please check with your doctor.

*We always advise checking with your physician when choosing products for the duration of pregnancy and breastfeeding.

References

1. Ocean quahog ^

2. Biomedicines 2022, 10(12), 3111; https://doi.org/10.3390/biomedicines10123111 . This article belongs to the Special Issue 10th Anniversary of Biomedicines—Aging Changes in Cells, Tissues and Organs. https://www.mdpi.com/2227-9059/10/12/3111 ^