Targeting skin ageing at the source: a novel cellular reprogramming approach using natural extract combinations

Skin aging is driven by cellular senescence, resulting in structural deterioration and aesthetic changes. This study investigated a new approach that combines natural small molecules to target RNA splicing regulation through upstream ERK/AKT signaling pathways. Both synthetic molecules and corresponding plant extracts were tested for their effects on senescent cells, proliferation, DNA damage, and SASP markers in aged human skin cells.

The researchers applied a simple, topical formulation to 3D human skin explants exposed to UVC irradiation. They found that a combination of extracts from H. lupulus and G. biloba had a dose-dependent senomorphic effect, reducing senescence by up to 45% in aged dermal fibroblasts and 10% in aged human primary keratinocytes (p values of 0.0001 or less). Notably, this combination did not promote cell proliferation.

Moreover, the formulation led to a 50% decrease in DNA damage load (p values of 0.0001 or less). Qualitatively, it also counteracted UV-induced epidermal hyperplasia, restored collagen fiber organization, and reduced markers of senescence and inflammation.

The study highlights the potential of targeting cellular senescence and splicing dysregulation using natural plant extracts as a novel way to reprogram senescent cells, ultimately repairing and protecting skin structure and function.