The skin is a natural barrier against the ultraviolet (UV) radiation of sunlight. The long-term and/or repetitive exposure to the sunlight and related UV radiation may change the skin structure, decreasing collagen production, promoting premature skin aging, which is termed “photoaging”. The signs of photoaging include wrinkle formation, mottled pigmentation, and/or cancerous changes. For many years, adipose-derived mesenchymal stem cells (AD-MSCs) and fat grafting (F-GRF) have been used to combat photoaging signs, wrinkles, loss of elasticity, and face soft tissue defects. Several studies have analyzed in vitro actions of AD-MSCs against photoaging’s effects, thanks to their migratory activity, paracrine actions, and related in vivo–ex vivo outcomes. In fact, AD-MSCs act against skin photoaging in vitro via activation of dermal fibroblast proliferation, antioxidant effect, and matrix metalloproteinases (MMPs) reduction. In vivo and ex vivo outcomes regard the local injection of AD-MSCs, F-GRF, and/or enriched-F-GRF with AD-MSCs directly in the wrinkles and the face’s soft tissue defects. This concise review summarizes the most recent in vitro, in vivo and ex vivo outcomes and developments on the effects of AD-MSCs and F-GRF against photoaging. The long-term and/or repetitive exposure to the sunlight and related UV radiation may change the skin structure, decreasing collagen production, promoting premature skin aging, which is termed “photoaging”. The signs of photoaging include wrinkle formation, mottled pigmentation, and/or cancerous changes. For many years, adipose-derived mesenchymal stem cells (AD-MSCs) and fat grafting (F-GRF) have been used to combat photoaging signs, wrinkles, loss of elasticity, and face soft tissue defects. Several studies have analyzed in vitro actions of AD-MSCs against photoaging’s effects, thanks to their migratory activity, paracrine actions, and related in vivo–ex vivo outcomes. In fact, AD-MSCs act against skin photoaging in vitro via activation of dermal fibroblast proliferation, antioxidant effect, and matrix metalloproteinases (MMPs) reduction. In vivo and ex vivo outcomes regard the local injection of AD-MSCs, F-GRF, and/or enriched-F-GRF with AD-MSCs directly in the wrinkles and the face’s soft tissue defects. This concise review summarizes the most recent in vitro, in vivo and ex vivo outcomes and developments on the effects of AD-MSCs and F-GRF against photoaging. The acute exposure to UV radiation leads to sunburn and local tissue damage, while long-term and/or repetitive exposure may change the skin structure, decreasing collagen production and promoting premature skin aging, which is termed “photoaging” [ 2 ]. Therefore, the UV exposure damages the skin’s stratum corneum, reduces its protective capacity, and leads to water loss. Large doses of UV radiation may enter deeply into the dermis, contributing to collagen degeneration as well as wrinkle formation [ 3 ]. Additionally, hereditary factors may facilitate the onset of photoaging’s signs, represented by wrinkle formation, major roughness, loss of elasticity, soft tissue defects with volume loss, and aging. UV is mainly composed of UV-A (wavelengths ranging from 320 to 420 nm) and UV-B (wavelengths ranging from 275 to 320 nm), altering specific parts of the skin tissue and leading to diverse consequences. In fact, UV-B radiation mainly affects the epidermis; when it is repetitive, it causes redness and a reduction of the skin’s elasticity, and it promotes wrinkle formation. UV-A radiation may penetrate deeply into the dermis and damage DNA, causing photoaging. The number of investigations evaluating the efficacy of autologous adipose-derived mesenchymal stem cells (AD-MSCs) contained in the stromal vascular fraction (SVF) of fat grafting (F-GRF) in the face’s soft-tissue defects and signs of aging has exponentially increased during the last twenty years (2000–2020). Autologous F-GRF is an interesting procedure in regenerative plastic surgery eagerly used in a growing number of indications, from skin rejuvenation and lipofilling to wound treatment [ 5 ]. Most of fat grafts’ regenerative capacity is attributed to AD-MSCs, suspended in a fatty tissue cellular matrix—SVF [ 6 ]. In in vitro models, the protective role of AD-MSCs via AD-MSCs-CM treatment in UVB-radiated human keratinocyte cells and HDFs has been investigated. The keratinocyte cells and dermal fibroblasts, which maintain the structural integrity of skin tissue, are considered In in vivo studies and related clinical trials, Luiz Charles-de-Sá et al. [ 30 ] have injected AD-MSCs expanded in vitro to the facial skin of patients after local operation. The analysis of elastic matrix components displayed a thorough regeneration of elastic oxytalan and elaunin fibers in the sub-epidermal region and the reconstruction of normal elastin fiber network in the dermis, indicating that AD-MSCs function as an appropriate access to structural restoration of photo-damaged skin [ 30 ]. At the same time, it has been possible to highlight that there is a lack of a standardized and widely shared protocol for the isolation methods/preparation method of AD-MSCs and SVF, as well as the lack of standardized evaluation procedures. 4. The Protective Role of AD-MSCs in Oxidative Stress: In Vitro and In Vivo Analysis In addition to the effects on ECM, UV also generates intracellular reactive oxygen species (ROS), a crucial factor leading to damage in photoaged skin tissue [ 31 ]. The Effect of Exosomes on Skin Photoaging The topical application of exosomes secreted by MSCs (MSC-Exos) on the skin is a very new and interesting topic in the medical field. Zhang et al. [ 38 ] investigated whether marine sponge Haliclona sp. spicules (SHSs) could effectively enhance the skin delivery of human umbilical cord-derived MSC-Exos (hucMSC-Exos), and further evaluated the topical application of hucMSC-Exos combined with SHSs in rejuvenating photoaged mouse skin.

Background Skin aging is the primary external manifestation of human aging, and long-term exposure to ultraviolet radiation is the leading cause of photoaging, which can lead to actinic keratosis and skin cancer in severe cases. Traditional treatments may pose safety risks and cause side effects. As an emerging research direction, plant-derived exosome-like nanoparticles (PDNPs) show promise in combating aging. Aloe vera, known for its natural active ingredients that benefit the skin, aloe-derived exosome-like nanoparticles (ADNPs) have not yet been studied for their potential in delaying skin aging. Methods In this study, nanoparticles were isolated from two different sites, aloe vera gel and aloe vera rind (gADNPs and rADNPs), and characterized by TEM, SEM, AFM, NTA and BCA. The effects were evaluated by constructing in vitro and in vivo models and using RT-qPCR, immunofluorescence, and histopathological analysis. Results The results first revealed the exceptional anti-aging effects of ADNPs. We found that ADNPs promoted the nuclear translocation of Nrf2, alleviated oxidative stress and DNA damage induced by UV exposure, and inhibited the elevation of β-gal and SASP. In vivo, ADNPs reduced MDA and SOD levels in mouse skin tissue and delayed skin photoaging. Moreover, safety assessments confirmed the excellent biocompatibility of ADNPs. Conclusion ADNPs delay skin photoaging through the Nrf2/ARE pathway, holding potential clinical application value, and may provide new therapeutic strategies for future medical cosmetology and skin disease prevention.

Photoaging is mainly induced by continuous exposure to sun light, causing multiple unwanted skin characters and accelerating skin aging. Adipose-derived stem cells(ADSCs) are promising in supporting skin repair because of their significant antioxidant capacity and strong proliferation, differentiation, and migration ability, as well as their enriched secretome containing various growth factors and cytokines. The identification of the mechanisms by which ADSCs perform these functions for photoaging has great potential to explore therapeutic applications and combat skin aging. We also review the basic mechanisms of UV-induced skin aging and recent improvement in pre-clinical applications of ADSCs associated with photoaging. Results showed that ADSCs are potential to address photoaging problem and might treat skin cancer. Compared with ADSCs alone, the secretome-based approaches and different preconditionings of ADSCs are more promising to overcome the current limitations and enhance the anti-photoaging capacity. Compared with ADSCs alone, the secretome-based approaches and different preconditionings of ADSCs are more promising to overcome the current limitations and enhance the anti-photoaging capacity. Keywords: Adipose-derived stem cell, Photoaging, Exosome, Conditioned medium, Reactive oxygen species, Aging, Secretome, Skin aging status released display-pdf yes is-olf no is-manuscript no is-preprint no is-journal-matter no is-scanned no is-retracted no Received 2020 Aug 9; Accepted 2020 Oct 23; Collection date 2020. Introduction The skin is our largest organ by weight and extent. It not only protects us from environment factors, but also synthesizes, processes, and metabolizes structural biomolecules such as lipid, protein, and glycan [ 1 ]. As a multifaceted organ, the skin also has sensory function and exerts pivotal role in esthetic appearance. Skin aging is a culmination of intrinsic and extrinsic elements, which result in decreased structural integrity and disruption of normal physiological function. Extrinsic factors such as solar radiation, cigarette [ 2 ], or other pollution factors could induce skin aging. Among them, exposure to UV (long wavelength ultraviolet radiations (UVA) and medium wavelength ultraviolet radiations (UVB) exposure) radiation (UVR) is the major source of extrinsic skin aging, which is also known as photoaging. Photoaging accounts for nearly 80% of facial aging [ 3 ]. It is characterized by fine wrinkles, dryness, laxity, rough texture, decreased elasticity, impaired wound healing, and benign and malignant growths [ 4 In daily life, the condition of the skin is an important element used to estimate people’s age and health [ 8 ]. With the development of modern society and increasing life expectancy, maintaining a youthful and vigorous appearance is highly desired, which has facilitated the dramatic growth of the cosmeceutical industry. Plant extracts [ 9 ], antioxidants [ 10 ], growth factors and cytokines [ 11 ], and stem cells [ 12 ] can be used to treat photoaging. Recently, stem cell therapy has attracted great attention because it can improve the regeneration ability of various tissues [ 12 – 14 ]. It is reported that stem cells and their derivatives are able to ameliorate skin conditions to some extent [ 15 ]. People are quite interested in the application of adipose-derived stem cells (ADSCs) in fields of dermatological and esthetic medicine, because they can be isolated and expanded easily and have clear multi-lineage differentiation [ 16 – 18 ]. Furthermore, it is reported that ADSCs can synthesize and secrete a lot of biologically active substances, mainly including antioxidants and cytokines that can be extracted and stored safely for a long time [ 19 ]. UVR accelerates skin aging by causing direct and indirect damage to multiple skin structures. The simplified diagram of the general model of UV-induced skin aging is shown in Fig. 1 . Fig. 1 UV-induced skin aging model Direct damage induced by UVB Direct damage is mainly caused by UVB. A considerate part of UVB is absorbed in the stratum corneum, and the rest part of UVB is absorbed in epidermal cells [ 27 ], inducing biological alternation in DNA, RNA, protein. DNA alternation is the most crucial one because accumulations of DNA damage can cause cell senescence and apoptosis. What is more, DNA alternation can damage the apoptotic capacity of skin cells and increase the possibility of malignancies [ 28 ]. Reactive oxygen species (ROS)-related indirect damage UVR can also cause physiological damage and accelerate skin aging indirectly via endogenous or exogenous photosensitizers that absorb solar radiations. The progress generates free radicals and ROS that induce skin inflammation. The inflammation progress can produce ROS by phagocytic cells and polynuclear lymphocytes [ 29 ]. The efficacy of ADSCs under multiple skin aging conditions have been presented and confirmed and are significant in potential therapeutic applications development, such as anti-wrinkling, dermal thickness improvement, skin whitening, UV-induced skin injury regulation, and tumor applications. A randomized controlled trial study showed that protein extracts of ADSC-CM via microneedles presented a critical improvement for melanin levels, brightness, skin gloss, roughness, elasticity, and wrinkles without the unfavorable side of the skin. Dermal fibroblasts play an important role in the fibroblast-keratinocyte-endothelium complex by providing these factors and promoting interactions between cells, which promotes wound repair as well as keeps the dermal integrity and skin youth. Normal applications dealing with dermal aging like laser and topical regimens usually promote the synthesis of ECM through activation of fibroblast. It was reported that ADSCs activated HDF through the generation of various growth factors which promote the proliferation and relocation of HDF and regulate the secretion of collagen in HDF [ 86 ].

Sunlight, despite its benefits, can pose a threat to the skin, which is a natural protective barrier. Phototoxicity caused by overexposure, especially to ultraviolet radiation (UVR), results in burns, accelerates photoaging, and causes skin cancer formation. Natural substances of plant origin, i.e., polyphenols, flavonoids, and photosynthetic pigments, can protect the skin against the effects of radiation, acting not only as photoprotectors like natural filters but as antioxidant and anti-inflammatory remedies, alleviating the effects of photodamage to the skin. Plant-based formulations are gaining popularity as an attractive alternative to synthetic filters. Over the past 20 years, a large number of studies have been published to assess the photoprotective effects of natural plant products, primarily through their antioxidant, antimutagenic, and anti-immunosuppressive activities. This review selects the most important data on skin photodamage and photoprotective efficacy of selected plant carotenoid representatives from in vivo studies on animal models and humans, as well as in vitro experiments performed on fibroblast and keratinocyte cell lines. Recent research on carotenoids associated with lipid nanoparticles, nanoemulsions, liposomes, and micelles is reviewed. The focus was on collecting those nanomaterials that serve to improve the bioavailability and stability of carotenoids as natural antioxidants with photoprotective activity.

Photoaging (PA) is considered a silent disease affecting millions of people globally and is defined as skin damage due to prolonged exposure to ultraviolet radiation (UVR) from the sun. Physiologically, the skin is in a state of renewal and synthesis of components of the extracellular matrix (ECM). However, exposure to UVR affects the production of the ECM, and the functioning and response of skin cells to UVR begins to change, thus expressing clinical and phenotypic characteristics of PA. The primary mechanisms involved in PA are direct damage to the DNA of skin cells, increases in oxidative stress, the activation of cell signaling pathways responsible for the loss of skin integrity, and cytotoxicity. The medical and scientific community has been researching new therapeutic tools that counteract PA, considering that the damage caused by UVR exceeds the antioxidant defense mechanisms of the skin. Thus, in recent years, certain nutraceuticals and phytochemicals have been found to exhibit potential antioxidant and photoprotective effects. Therefore, the main objective of this review is to elucidate the molecular bases of PA and the latest pharmaceutical industry findings on antioxidant treatment against the progression of PA.

Sunlight is a vital element in modulating the central circadian rhythm, such as the regulation of the host’s sleep–awake state. Sunlight is also considered to have a significant influence on the circadian rhythm of the skin. Over-exposure or prolonged exposure to sunlight can lead to skin photodamage, including hyperpigmentation, collagen degradation, fibrosis, and even skin cancer. Thus, this review will focus on the adverse effects of sunlight on the skin, not only in terms of photoaging but also its effect on the skin’s circadian rhythm. Mitochondrial melatonin, regarded as a beneficial anti-aging substance for the skin, follows a circadian rhythm and exhibits a powerful anti-oxidative capacity, which has been shown to be associated with skin function. Thus, the review will focus on the influence of sunlight on skin status, not only in terms of ultraviolet radiation (UVR)-induced oxidative stress but also its mediation of circadian rhythms regulating skin homeostasis. In addition, this article will address issues regarding how best to unleash the biological potential of melatonin. These findings about the circadian rhythms of the skin have broadened the horizon of a whole new dimension in our comprehension of the molecular mechanisms of the skin and are likely to help pharmaceutical companies to develop more effective products that not only inhibit photoaging but keep valid and relevant throughout the day in future.