Nicotinamide adenine dinucleotide (NAD⁺) is indispensable for the regulation of biological metabolism. Previous studies have revealed its role in aging and degenerative diseases, while crucially showing that supplementation with NAD⁺ or its precursors could ameliorate or reverse the progression of aging. Despite extensive evidence for the role and action of NAD⁺ in aging, its pharmacological activity on the skin, or even its mechanism, has not been elucidated. In this study, we established a novel approach to effectively utilize NAD⁺ for skin anti-aging by enhancing the pharmacological efficacy of exogenous NAD⁺ using a phytochemical complex consisting of quercetin, and enoxolone through inhibition of CD38. Through the comprehensive in vitro experiments based on human fibroblasts, we observed that exogenous NAD⁺ could exert protective effects against both extrinsic aging induced by ultraviolet light exposure and intrinsic aging. Additionally, we found that its effects were significantly boosted by quercetin and enoxolone. In this in-depth study, we demonstrated that these beneficial effects are mediated by improved sirtuin activation, autophagy, and mitochondrial functionality. Our approach is expected to verify the applicability of the topical application of NAD⁺ and offer more effective solutions for the unmet needs of patients and consumers who demand more effective anti-aging effects.

Pain and itch are aversive sensations with distinct qualities, processed in overlapping pathways and brain regions, including the anterior cingulate cortex (ACC), which is critical for their affective dimensions. However, the cellular mechanisms underlying their processing in the ACC remain unclear. Here, we identify modality-specific neuronal populations in layer II/III of the ACC in mice involved in pain and itch processing. Using a synapse labeling tool, we show that pain- and itch-related neurons selectively receive synaptic inputs from mediodorsal thalamic neurons activated by pain and itch stimuli, respectively. Chemogenetic inhibition of these neurons reduced pruriception or nociception without affecting the opposite modality. Conversely, activation of these neurons did not enhance stimulus-specific responses but commonly increased freezing-like behavior. These findings reveal that the processing of itch and pain information in the ACC involves activity-dependent and modality-specific neuronal populations, and that pain and itch are processed by functionally distinct ACC neuronal subsets.

Background/Objectives: Enhancement of cellular NAD⁺ mediated by NMN has emerged as a pivotal strategy in modulating the aging process. This study aimed to systematically investigate the anti-aging effects of NMN on human skin fibroblasts, focusing on how the former contributes to the improvement of cellular health and function. This study elucidated the molecular and functional mechanisms by which NMN contributes to the attenuation of skin aging. Methods: We performed extensive in vitro and transcriptomic analyses. Human skin fibroblasts were treated with NMN, and the induced biological responses were observed under oxidative stress/photo-aging models. Results: Transcriptome analysis revealed distinct gene expression patterns for NAD⁺ and its precursors (NMN, NR, and NAM), showing significant differences between NMN and other precursors (NR and NMN). NMN seemed to be significantly involved in cytokine and chemokine activity. It significantly elevated cellular NAD⁺ levels, activated sirtuin and autophagy pathways, and enhanced mitochondrial function, collectively maintaining cellular homeostasis under stress. Furthermore, it suppressed cellular senescence, promoted cell proliferation, supported extracellular matrix integrity, and accelerated wound healing. Conclusions: The study provided essential mechanistic evidence supporting the anti-aging effects of NMN in skin cells and addressed the current lack of scientific validation of NMN-based topical applications. The findings established a solid academic background for future translational research and the development of NMN-based therapeutics and cosmeceuticals.

Skin aging is a multifaceted biological phenomenon influenced by a combination of intrinsic or extrinsic factors. There is an increasing interest in anti-aging materials including components that improve skin wrinkles. Despite the availability of several such wrinkle-improving materials, the demand for ingredients with outstanding efficacy is increasing. Therefore, this study aimed to explore the mechanisms of wrinkle-related genes reported in previous genome-wide association studies (GWASs), identify materials that regulate these genes, and develop an effective anti-wrinkle formula containing the active ingredients that regulate the expression of these genes. We selected two candidate genes, EDAR and BNC2, that are reportedly related to periorbital wrinkles. We investigated their functions in the skin through in vitro experiments using human skin cell lines (keratinocytes and fibroblasts). Moreover, we identified ingredients that regulate the expression of these two genes and confirmed their efficacy through in vitro experiments using the skin cell lines. Finally, we developed a formula containing these ingredients and confirmed that it enhanced dermal collagen in the 3D skin and improved fine wrinkles under the eyes more effectively than retinol in humans, when applied for 8 weeks. Our results are significant and relevant, as we have discovered a special formula for wrinkle improvement with reliable efficacy that surpasses the efficacy of retinol and does not cause side-effects such as skin irritation.

Skin aging is an unavoidable natural phenomenon caused by intrinsic and extrinsic factors. In modern society, the pursuit of a wrinkle-free and aesthetically appealing face has gained considerable prominence. Numerous studies have aimed at mitigating the appearance of facial wrinkles. Antiaging research focused on regulating the function of mitochondria, the main reactive oxygen species-generating organelles, has been extensively conducted. In this study, we investigated the correlation between facial wrinkles and the expression of PPARGC1B, considering the association of this gene with mitochondrial function, to identify its potential as a target for exploring antiaging cosmetic materials. We elucidated the role of PPARGC1B in the skin and identified five bioactive materials that modulated its expression. The effectiveness of these materials was verified through in vitro experiments on human dermal fibroblasts. We prepared cosmetic formulations incorporating the five materials and confirmed their ability to enhance dermal collagen in three-dimensional skin models and reduce facial wrinkles under the eyes and nasolabial fold areas in human subjects. The study findings have significant implications for developing novel antiaging cosmetic formulations by reinforcing mitochondrial functions.

Skin aging is a complex process with internal and external factors. Recent studies have suggested that enlargement and elongation of skin pores may be early signs of aging in addition to wrinkles and loss of elasticity. This study explores the potential of targeting the SGPP2 gene in keratinocytes to address these emerging concerns. Using siRNA knockdown, we demonstrated that SGPP2 modulates the production of inflammatory cytokines (interleukin (IL)-1β and IL-8). Furthermore, conditioned media experiments revealed that keratinocytes with high SGPP2 expression indirectly influence fibroblast extracellular matrix remodeling, potentially contributing to enlarged pores and wrinkle formation. Based on these findings, we explored a complex formulation containing four SGPP2-modulating compounds. In vitro and in vivo experiments demonstrated the efficacy of the formulation in mitigating fine wrinkles and pore enlargement. This study highlights the significant implications of developing a more effective antiaging cosmetic formulation by targeting underlying inflammatory processes that drive skin aging.