Plant Small RNA-Rich Himalayan Anethum graveolens Extract Modulates Aging-Associated microRNA Signatures to Enhance Dermal Architecture Protein Synthesis in Human Skin

In December 2024, scientists Victor Ambros and Gary Ruvkun were awarded the Nobel Prize in Physiology or Medicine for their novel discovery of post-transcriptional gene regulation via microRNA (miRNA). This large class of non-coding RNAs defines a new layer of gene regulation activity that can control many biological processes in multicellular organisms. This experimental study explores how Himalayan Anethum graveolens extract (HAGE), rich in small RNAs, obtained by PSR technology™, can modulate human miRNAs and skin signaling pathways to improve dermal architecture and elastic fiber integrity for anti-aging benefits. Our epigenomic study analyzes skin biopsies from Chinese individuals according to different characteristics (chronological age, photoprotection…) and identifies distinct miRNA expression profiles associated with both endogenous and exogenous aging pathways using analytical and bioinformatics methodologies. Differential targeting of aging-related genes suggests that specific miRNAs may play a regulatory role in coordinating these two aging processes. Our in vitro experiments in normal human dermal fibroblasts indicate that 0.05% HAGE decreased the expression of miRNA signatures associated with intrinsic aging (miR-30c-2-3p and miR-125b-1-3p) and photoaging (miR-16-2-3p). Further in vitro and ex vivo assays, with the ex vivo findings to be regarded as preliminary, also showed increases in dermal matrix proteins such as collagen type I and III, elastin, fibrillin-1 and dermatopontin. We demonstrated that HAGE decreases key aging-associated miRNAs, including miR-30c-2-3p and miR-125b-1-3p (intrinsic aging) and miR-16-2-3p (photoaging). IGF1 and IGF1R are established miRNA targets, identified as skin endogenous aging target genes of miR-30c-2-3p and miR-125b-1-3p (invention patent ZL201810165800.7, IDP000089683) and are involved in cell growth and renewal, whereas CTGF (CCN2) is an experimentally supported target of miR-16-2-3p; however, the restoration of these target axes by HAGE was not directly measured. In ex vivo and in vitro models, HAGE increased collagen type I and III, elastin, fibrillin-1 and dermatopontin, supporting its potential regulatory impact on skin aging mechanisms. Our experiments are consistent with an epigenetic modulation model of aging prevention based on the modulation of miRNAs as aging gene-silencing agents by topical application of extracts rich in small RNAs such as HAGE. Whether plant small RNAs are taken up by and functional in human skin cells, and whether this modulation translates into clinical anti-aging benefits remains to be established.