96 ANTI-AGEING Collectively known as the senescence-
associated secretory phenotype (SASP), these secretions can reinforce the arrest while also causing molecular damage, impairing skin tissue function, and contributing to skin ageing.13,14 Senolytics, compounds that selectively
eliminate senescent cells by reactivating suppressed apoptotic pathways, aim to reverse the effects of exposomal insults and restore a youthful appearance to the skin.15,17 DermalRx® Acetygen® - hereafter known as
the dual botanical extract - rich in myricetin and dihydromyricetin, delivers senolytic effects in skin cells. The dual extract of Agrimonia eupatoria and Ampelopsis grossedentata (plants belonging to the rose and grape families, respectively) increases apoptosis in senescent-prone cells, particularly in UV-damaged keratinocytes (Figure 3A). Notably, the apoptosis is specific to UV-
exposed cells and does not occur in cells that were not subjected to UV (Figure 3A). To specifically eliminate senescent cells, the dual botanical extract increases phosphorylation of the p53 protein at serine 46, a modification known to drive apoptosis of senescent cells (Figure 3B).
Epigenetics of skin ageing The exposome accelerates skin ageing by modifying the tissue’s epigenetics. Epigenetic modifications dynamically regulate patterns of gene expression. Epigenetic mechanisms can be thought of as an orchestra conductor that directs the way musicians play, where the DNA is the information-rich sheet music filled with musical notes, the individual genes. Like the conductor dictating how a song
is played, the epigenome controls gene expression (Figure 4B). While some notes might be played with varying volume or timing, genes in the skin can be highly expressed or turned off depending on the epigenetic modifications in that cell. Finely tuned gene expression is necessary to
keep skin looking healthy. Specific levels of gene products are required to maintain essential cellular and skin-specific processes, like barrier function, pigment production, and epidermal renewal. For example, epigenetic harmony is vital for skin elasticity. Studies have found that UV exposure alters the expression of versican, a component of
A
Induction of apoptosis in UVB-damaged keratinocytes with the dual botanical extract
25 20 15 10 5 0
** ns
Normal cells
UV-damaged cells
ns, not significant **p<0.01
100 75 50 25 0
Figure 3: The dual botanical extract mitigates exposome-induced senescence PERSONAL CARE March 2024
www.personalcaremagazine.com
Figure 2: Skin structure at the cellular level
elastic fibers, and this imbalance is associated with a loss of elasticity and increased wrinkle formation in photoaged skin.18 The epigenetic modifications orchestrating
gene expression include reversible alterations of DNA methylation and histone modifications along with non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs).19,20 The exposome affects the skin’s epigenetic
profile, with environmental and lifestyle factors shaping the epigenome over a lifetime. In particular, epigenetic dysregulation induced by the exposome plays a critical role in senescence initiation and maintenance.21 Senescent cells have been demonstrated
to have global changes in the epigenome, with DNA-SCARS (DNA segments with chromatin alterations reinforcing senescence) sustaining cellular arrest and inflammatory cytokine secretion.22 Decreased histone acetylation has been noted in senescent cells.23
the development of restorative epigenetic approaches for protective skincare.
MicroRNAs in the skin MiRNAs are small, non-coding RNAs that play crucial roles in regulating gene expression. For a gene to be expressed, a segment of the DNA sequence (the ‘gene’) is transcribed to a messenger RNA (mRNA) that exits the nucleus to be translated to a protein in the cell’s cytoplasm (Figure 4B). MiRNAs control gene expression through
selective mRNA degradation or sequestration. In each case, the miRNA binds to a target mRNA through sequence-specific interactions and dampens that gene’s expression (Figure 5A). Thus, increasing the amount of a miRNA reduces the expression of its target genes.26 Studies have found that the skin’s miRNA
Additionally, altered
miR-34 levels in the dermis are correlated with cellular senescence and other age-related decline in human dermal fibroblasts (HDFs).24 The interplay between the exposome
and epigenetic mechanisms significantly contributes to premature skin ageing.3,25 Scientific research investigating the complex exposome-epigenome interactions supports
B
Modulation of p53 activity for senolytic effects with the dual botanical extract
profile is altered by dangerous exposomal factors, such as UV radiation, airborne particulate matter, diesel fumes, and ozone.27-29 A study using human skin biopsies found that immediately following ozone and UV exposure, 559 and 532 miRNAs were dysregulated, respectively.28
miRNAs remained out of balance in each case. Researchers have identified many miRNAs
that play critical roles in skin homeostasis.30 MiRNAs are involved in nearly every skin process, including oxidative stress response,
Notably, after 24 hours, over 400
Concentration of the dual botanical extract (%) 0.50
0.125 0.25
Increase in apoptosis (relative to controls) (%)
Relative phosphorylation levels (%)
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