Condensed Review of Cutaneous Formulations Addressing Gender Differences and Exposome Factors in the Asia Pacific

Demand for products that target visible signs of skin aging such as wrinkles, ptosis, vascular disorders, and uneven pigmentation has grown in parallel with increasing longevity and interest in youthful appearance. Skin is the first organ in direct contact with solar radiation and air pollution, so early manifestations of aging are often cutaneous. All exposures from conception to death, integrating internal biological factors and external environmental factors, are encompassed in the concept of the exposome, and these exposures influence the pathophysiology of skin aging, with oxidative processes playing a major role. Vitamin C and bioactive peptides have emerged as key antioxidant and anti-aging ingredients within this context, underscoring the importance of formulation for cutaneous performance [1].

Ambient air pollution is now recognized as a major global health risk, with particulate matter, volatile organic compounds, ozone, nitrogen dioxide, and sulfur dioxide varying by geography and level of industrialization. Outdoor pollution predominantly affects urban environments and forms complex mixtures including fine PM2.5 and coarse particles that can be coated with anthropogenic pollutants and microbial components. Secondary pollutants such as ozone and peroxyacetyl nitrates arise from photochemical reactions between primary pollutants, heat, and UV radiation and accumulate as smog in the troposphere. Despite extensive data on respiratory and cardiovascular effects, cutaneous consequences of pollution and their relevance for sensitive skin are only beginning to be systematically reviewed, motivating interest in cosmetic strategies that prevent or relieve pollution-induced damage. Sensitive skin, associated with barrier dysfunction, shows increasing prevalence in industrialized countries, including Asian skin types, indicating a specific need for tailored management in highly polluted urban areas [2].

Oxidative stress links lifestyle, environmental exposures, and cellular aging pathways. Reactive oxygen species generated by mitochondrial dysfunction can contribute to inflammatory signaling, cellular dysfunction, and apoptosis and, thereby, to disease development and aging. Poor diet, smoking, infection, and chronic inflammation act as upstream drivers of mitochondrial fragmentation, membrane permeabilization, and reduced respiratory capacity, with downstream increases in mitochondrial ROS and altered antioxidant enzyme activities. This framework has been used to describe how antioxidants such as astaxanthin may inhibit oxidative stress-induced mitochondrial dysfunction and thereby modulate disease and aging trajectories. Within dermatology, anti-aging skincare focuses strongly on UV protection, free radical scavenging, and cell-protecting agents, including both synthetic and natural compounds that enhance antioxidant enzyme levels and mitigate UV-mediated damage. Novel delivery systems and nanomaterials are increasingly deployed in cosmetic formulations to improve penetration, stability, and sensory attributes, and transdermal nanoformulations for hormonal therapy have been reported as safe and effective options for relieving menopausal symptoms and restoring serum hormone levels. These developments highlight that the choice of actives, verification of activity and stability in formulation, and ability to reach living skin layers where ROS are generated are critical determinants of clinical anti-aging efficacy [3].

Gender-specific physiology further modulates how exposomes impact skin and how formulations should be designed. Aging involves intrinsic chronological processes and extrinsic factors such as chronic sun exposure, leading to wrinkles, sagging, and drooping. Hormonal changes with age, including declines in estrogen, testosterone, DHEA, and DHEAS, alter sebum production, hydration, skin thickness, and antioxidant defenses. Estrogen functions as an innate antioxidant, regulating molecules like superoxide dismutase, whereas men exhibit higher susceptibility to free radical damage and steeper declines in aerobic capacity. Structural differences such as thinner epidermis and dermis, lower hair follicle density, reduced sebum and sweat production, and distinct hypodermal fat distribution contribute to divergent wrinkle patterns and atrophy in males and females. External factors including sunlight, lifestyle, and pollutants accelerate these intrinsic trajectories and influence predisposition to acne, actinic keratosis, eczema, psoriasis, and premature aging syndromes. These findings underscore the need for gender-specific cosmetic and therapeutic strategies that account for differential responses to extrinsic aging drivers [4].

Against this backdrop, formulation science must align antioxidant, peptide, retinoid, and hormonal technologies with regional pollution profiles, lifestyle patterns, and gender-specific biology to optimize cutaneous outcomes in diverse Asia Pacific populations.