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A Pilot Study Evaluating Efficacy of a Topical Klotho Anti-Aging Serum to Treatable Visible Photoaging

September 2025 | Volume 24 | Issue 9 | 8797 | Copyright © September 2025


Published online August 18, 2025

doi:10.36849/JDD.8797R1

Gail Humble MDa, Shanaya Dias b, Sera Quintana a, Tatiana V. Tatarinova PhDc, Pearl Grimes MDb

aAesthetic Anti-Aging Institute, Mill Valley, California, CA
bVitiligo and Pigmentation Institute of Southern California, Los Angeles, California, CA
cDepartment of Biology, University of La Verne, La Verne, California, CA

Abstract
Background: Up to 90% of skin aging is caused by ultraviolet radiation, resulting in significant photodamage and clinical burden. Klotho Skin Serum, formulated with the Klotho protein for anti-aging, shows promise based on preclinical studies exploring its physiological functions and therapeutic applications.
Objective: To investigate the efficacy and safety of Klotho Skin Serum in improving visible signs of photoaging.
Methods: Female participants (N=16) aged 30 to 60 years with mild to moderate photodamage received Klotho Skin Serum twice daily for 12 weeks. The primary efficacy endpoint was the investigator evaluated global improvement in skin aging (fine lines and wrinkles) at Week 12.
Results: Global improvements in skin aging were reported with Klotho Skin Serum throughout the study. At Week 12, statistically significant improvements from baseline were observed with Klotho Skin Serum (p<0.001) with significant improvements also reported at all timepoints. The application of Klotho Skin Serum led to robust improvements in key secondary outcomes from baseline to Week 16, including notable reductions in photodamage, erythema, wrinkles, and dyschromia.
Conclusions: Klotho protein containing serum is an efficacious and safe treatment option to address photodamage and to improve the visible signs of photodamage and skin aging. Large-scale clinical studies are warranted to further evaluate its use in skin aging.

J Drugs Dermatol. 2025;24(9): doi:10.36849/JDD.8797R1

INTRODUCTION

Ultra-violet (UV) radiation is a key factor in skin aging, responsible for up to 90% of the process. Its effects are diverse, including loss of elasticity, fine lines, wrinkles, reduced epidermal and dermal components, increased epidermal permeability, and delayed wound healing.1 The health risks associated with excessive UV exposure are profound, with UV being the most important modifiable risk factor for skin cancer and many other environmentally influenced skin disorders.2

The clinical burden of photodamage and skin aging is significant and multifaceted, impacting an individual’s physical appearance, psychological well-being, and overall quality of life.3,4 Photodamage accelerates the natural aging process of the skin, leading to a variety of clinical manifestations, including fine lines, wrinkles, hyperpigmentation (freckles, age spots, and melasma), loss of elasticity and firmness, and texture irregularities.1,5-7 Beyond the physical manifestations, the burden of photodamage and skin aging extends to psychosocial impacts. Visible signs of aging, such as wrinkles and pigmentation irregularities, can negatively affect an individual’s self-esteem, impair quality of life, and may also lead to anxiety, depression, and avoidance of social situations.8-10

The Klotho gene, named after the Greek goddess who spun the thread of human life, encodes a transmembrane protein primarily expressed in the kidneys and, to a lesser extent, in other tissues, including the brain, parathyroid gland, and endothelial cells. Discovered by Kuro-o et al in 1997, the Klotho gene is of particular interest in the fields of gerontology and aging due to its association with aging and age-related diseases.11 Mutant mice lacking the Klotho gene exhibited premature aging phenotypes, including a shortened lifespan, osteoporosis, arteriosclerosis, and cognitive decline. Preclinical studies in animal models have provided evidence supporting the role of Klotho in skin health and aging; Klotho deficiency