34 ANTI-AGEING
targeting of the gene pathways for important extracellular matrix (ECM) fibre proteins like type I collagen and elastin.5
miR-132 gained
attention because of its dual capacity to diminish inflammation and enhance keratinocyte proliferation, which are key to efficient wound healing.6 Notably, miR-146a-5p has received
considerable attention from its ability to inhibit the expression of multiple inflammatory gene products, thus becoming an attractive target for addressing multiple skin conditions rooted in acute and chronic inflammation.7
This particular
miRNA certainly represents a valuable target as the industry addresses the 12 ‘Hallmarks of Ageing’ that includes low level, chronic inflammation known as ‘inflamm-ageing’. More recently, miR-205 was implicated in
the process of hair regeneration, making it a new research focus for countering hair loss.8
recent health concerns of sexual, reproductive, endocrine, carcinogenic, and neurological detriments associated 5-alpha reductase inhibitors used to restore hair growth, having a naturally occurring alternative becomes very attractive. Finally, for skin brightening applications,
miR-330-5p appears to be a critical factor as it has been demonstrated to down-modulate the expression of tyrosinase, the key enzyme in melanogenesis.9
Given the With a paucity of approved
materials that are capable of addressing hyperpigmentation, this miRNA potentially looks to be an attractive solution. Much of the research into applying RNAi
involves the topical delivery of miRNA ‘mimics’ and ‘antagomiRs’. The former employs precise replicas of naturally occurring miRNAs so that their relative abundance in the cell is increased thereby promoting the down-regulation of their targeted gene product.10 In contrast, the latter is an RNA construct that anneals in a sequence-specific manner to a natural miRNA, which prevents it from intercepting the mRNA, thus allowing for augmented protein synthesis of the miRNA target.11
Herein, we provide
scientific evidence of the successful use of an antagomiR to reverse the signs of ageing.
Target: miR-29a-3p The 29th miRNA identified in the human genome is designated miR-29a-3p. As mentioned above, lengthy characterization demonstrated that its primary gene targets correspond to key factors in the ECM of the skin, including type I collagen fibres and elastin.5 Therefore, elevated expression of miR-29a-
3p would diminish the levels of these important factors in skin strength and resiliency. It is also known that as we age, the relative abundance of miR-29a-3p increases, playing an epigenetic role in biological ageing. Cumulatively, these findings properly earned
this non-coding RNA the moniker of the ‘wrinkle microRN’. As such, any intervention that could lower the cellular concentration of miR-29a-3p could potentially have highly beneficial impacts on skin health.
PERSONAL CARE MAGAZINE January 2026
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Figure 1: Proof-of-concept experiment utilizing an antagomiR to miR-29a-3p to improve the expression of fibrillin in normal human dermal fibroblasts (NHDF). Mimics and antagomiRs of miR- 29a-3p were transfected into monolayers of NHDF cells and allowed to incubate for three days. Subsequently, the cells were harvested, lysed, and analyzed by Western blot probing with antibodies specific to fibrillin. The resulting bands were quantified by densitometry scanning, normalized to a loading control, and plotted on the graphs shown
To that end, an antagomiR complementary
to miR-29a-3p was constructed, intended to diminish its endogenous levels and presumably augment the abundance of its downstream targets. One of the first proof-of-concept experiments to determine if an anti-miR-29a-3p antagomiR could positively impact the expression levels of the ECM protein fibrillin is shown in Figure 1. In that experiment, the antagomiR to miR-
29a-3p dose-dependently increased fibrillin levels while mimics of miR-29a-3p decreased the fibrillin concentration in a dose-dependent manner. The in vitro testing was continued further showing that the cellular production of type I collagen and elastin could also be stimulated (data not shown). These investigations were corroborated
using a three-dimensional reconstructed human epidermis model system and ex vivo with human skin explants. The ex vivo studies confirmed that a topically applied formulation containing the miR-
29a-3p antagomiR diminished the abundance of the miRNA and improved the expression of multiple beneficial gene products including collagen, elastin, and fibrillin. In Table 2, alterations in gene expression in
response to the antagomiR-containing treatments are shown.
The positive findings from the in vitro and
ex vivo studies merited the commissioning of a clinical investigation. A 12-week, double blind, placebo-controlled study was conducted to evaluate the efficacy of miR-29a-3p antagomiR in formulation. The product was applied twice daily to assess
its ability to improve key parameters of skin health in female subject aged 40 to 67 who presented with visible lines and wrinkles. The subjects represented a broad demographic with Fitzpatrick skin types I-V. Efficacy assessments were conducted at baseline, four, eight and 12 weeks using a
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