ANTI-AGEING


A single ingredient for all types of skin ageing


Dr Sekyoo Jeong, Dr Keedon Park - Incospharm


In addition to the phenotypic skin-ageing classification of chronological (intrinsic) ageing and photo (extrinsic) ageing, several new terms describing multiple aspects of skin ageing have been introduced recently. These include inflamm- ageing (Figure 1), barri-ageing (Figure 2) and sensiti-ageing (Figure 3). While these terms do not completely explain


the complex mechanism of skin ageing, each tries to explain the major biological events associated with the ageing process and provides the mechanistic backgrounds for developing new anti- ageing cosmetic ingredients. As a result of these efforts, various kinds of bioactive ingredients have been introduced and efforts have been made to develop a single ingredient capable of addressing all these aspects of skin ageing at once. Autophagy, derived from Greek words meaning ‘self’ and ‘eating’, is a process which removes the unnecessary, worn-out micro- organelles or dysfunctional proteins through a lysosome-dependent regulated mechanism. Recently, studies have suggested an important role for autophagy in skin homeostasis and the potential use of autophagy-stimulating cosmetic ingredients has received a lot of attention.


Classical classification of skin ageing Among the various phenotypic changes associated with skin ageing, the most notable are the formation of wrinkles, abnormal pigmentation and the deterioration of physical properties, such as increased fragility and a loss of skin elasticity. However, changes in skin functions, such as increased skin dryness and the impairment of the skin barrier function are also representative symptoms of skin ageing. In intrinsic ageing, both the quantitative and the qualitative properties of dermal extracellular matrix of collagen and elastic fibres are impaired, due to the accelerated degradation (quantitative) and disorganisation (qualitative) of fibre and matrix proteins. This results in decreased skin elasticity and tensile strength. Reduced undulation of dermal-epidermal junction structure further results in higher fragility in aged skin. The formation of fine wrinkles and hypopigmentation by decreased number of melanocytes are other typical features of intrinsic ageing. While extrinsic ageing shares a lot of common


aspects with those of intrinsic ageing, several different points need to be addressed. First and most all, UV irradiation induces not only protein level damages but also genetic (DNA) damage, which


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Cellular damages


Autophagy activator


Inflamm-ageing


Pro-inflammatory cytokines


Cellular senescence


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Figure 1: Inflamm-ageing


may ultimately result in skin cancer. Phenotype changes include irregular pigmentation, coarse wrinkles and pre-malignant neoplasms, such as actinic keratosis. Most current cosmetic ‘anti-ageing’ ingredients


address one or more points of intervention: reducing the oxidative stress induced by UV irradiation; preventing the degradation or stimulating the synthesis of dermal extracellular matrix proteins; and interrupting intercellular signalling between neurons and muscle fibres. While new anti-ageing ingredients are continuously developed and introduced, however, few offer scientific background and solid data about their clinical efficacy.


Autophagy: Core machinery for skin homeostasis Autophagy is a catabolic process through which abnormal proteins, dysfunctional organelles and exogenous microorganisms are eliminated by lysosomal degradation machinery.1


Various


kinds of physiologic stimuli, including nutrient starvation and pharmacologic compounds, such as rapamycin, are reported to induce autophagy signalling. As an evolutionarily conserved, ubiquitous


catabolic process, the autophagic machinery mediates the majority of intracellular housekeeping tasks, as well as homeostatic responses, including immune responses, cellular proliferation and/or differentiation, and apoptosis. Since the discovery of ATG genes in yeast, understanding of the molecular mechanisms involved in autophagy has greatly advanced and pharmacologic applications of autophagy-modulating compounds for various diseases have been reported.


In skin, epidermal differentiation, like inflammation and immune functions, is known to be tightly regulated by autophagy activity. Mechanistic similarities between autophagy and terminal differentiation of epidermal keratinocytes, such as tightly regulated degradation of micro- organelles, further support the crucial roles of autophagy in epidermal differentiation. It has also been reported that autophagy signalling is involved in inflammatory responses in keratinocytes and activation of autophagy can induce anti-inflammatory effects partly through inflammasome-mediated signalling. In addition to epidermal differentiation, the potential involvement of autophagy in other homeostatic responses in skin has also been reported. Sebum formation in sebaceous gland cells2 melanogenesis3


and have recently been reported as


being regulated by autophagy signalling. Recently, we also reported that newly


synthesised pyrrolidone carboxylic acid (PCA)- mimetic peptide derivative (Aquatide™, hereafter referred to as the autophagy-activating peptide derivative) had an unexpected autophagy activating effects on epidermal keratinocytes and dermal fibroblasts.4


Through a series of studies,


we were able to identify the mode of action for autophagy activation and its potential benefits for skin health, including enhancing the cellular antioxidant system. Oxidative damages, induced by either


UV-irradiation or hydrogen peroxide, was significantly attenuated by the autophagy activator treatments and clinical anti-ageing activity, represented by increased skin elasticity, was also observed.5


However, stimulation of the cellular antioxidant system is not sufficient February 2022 PERSONAL CARE


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