The decline of proteostasis is a central hallmark of aging, the earliest manifestations of which have remained difficult to capture in human tissues with conventional model systems. The skin is a continuously renewing and environmentally exposed organ offering a uniquely accessible window into aging biology. Skin organoid technologies allow for long-term culturing of human epidermal and full-thickness skin-like tissues that accurately recapitulate important aspects of cellular heterogeneity, spatial organization, and stem cell dynamics. In this perspective, we discuss how skin organoids are beginning to reveal early proteostasis alterations-encompassing impaired protein folding, reduced proteasomal activity, and autophagy dysfunction-that precede overt structural and functional hallmarks of skin aging, with particular emphasis on underexplored regulators- sebaceous gland and sebocyte-specific proteostasis, autophagy, and inflammaging. We also highlight emerging insights, conceptual challenges, and experimental limitations, and outline future directions for integrating skin organoids with skin-on-a-chip, single-cell proteomics, and stress-reporting approaches to advance proteostasis-targeted interventions in skin aging.

Sleep deprivation or insomnia is one of the most common but neglected health conditions, with serious long-term consequences. In addition, insomnia is linked to poor work performance, impaired memory, and lack of concentration. Improving sleep quality is a crucial aspect of health care. Hypnotic agents, such as benzodiazepines, antidepressants, and antihistamines, are often used to enhance sleep quality; however, these medications often result in tolerance and dependence, resulting in withdrawal syndrome upon discontinuation. In recent years, studies have focused on natural and herbal therapies as alternative sleep aids to overcome the adverse effects of available sleep medications. Plant extracts contain phytochemicals that exert anxiolytic and sedative properties. This includes Passiflora incarnata (FSD-PI) and Lactuca sativa L. (FSD-LS) which can induce sleep. Herein, we assessed the effects of natural products, FSD-PI and FSD-LS, as well as their synergistic effects on pentobarbital sleep-induced ICR mice. We observed that natural extracts did not cause any behavioral changes capable of negative effects in mice. Furthermore, sleep duration was prolonged in pentobarbital-treated mice administered with FSD-LS (100 mg/kg). Our data suggest that FSD-LS may be a safe and effective sleep promoter.