皮肤,作为身体抵御外部因素的主要防御,在保护身体免受感染和伤害方面起着至关重要的作用,以及保持整体稳态。皮肤老化,衰老过程的常见表现,涉及其正常结构和修复机制的逐渐恶化。解决皮肤老化问题越来越势在必行。多项证据表明,外源性核苷酸(NT)通过其抑制氧化应激和炎症的能力具有潜在的抗衰老作用。本研究旨在探讨外源性NTs是否可以减缓皮肤老化并阐明其潜在机制。为了实现这一目标,利用衰老加速小鼠俯卧8(SAMP8)小鼠,并随机分配到衰老,NTs-低,NTs-middle,和NT-高集团,而衰老加速小鼠抗性1(SAMR1)小鼠作为对照组。经过9个月的NT干预,收集背侧皮肤样本以分析病理并评估与衰老过程相关物质的存在和表达。结果表明,高剂量NT治疗导致上皮和真皮层的厚度显着增加,以及Hyp含量(p<0.05)。此外,观察到低剂量NT干预导致衰老改善,p16表达显著降低(p<0.05)。重要的是,高剂量NT的管理可以改善,在某些方面,线粒体功能,已知其减少氧化应激并显著促进ATP和NAD+的产生。这些观察到的效应可能与NT诱导的自噬有关,干预组中p62的表达降低和LC3BI/II的表达增加证明了这一点。此外,发现NTs上调pAMPK和PGC-1α的表达,同时抑制p38MAPK的磷酸化,JNK,和ERK,提示自噬可能通过AMPK和MAPK通路进行调控。因此,NTs对自噬的潜在诱导作用可能有助于通过激活AMPK途径和抑制MAPK途径解决皮肤老化问题.
The skin, serving as the body\'s primary defense against external elements, plays a crucial role in protecting the body from infections and injuries, as well as maintaining overall homeostasis. Skin aging, a common manifestation of the aging process, involves the gradual deterioration of its normal structure and repair mechanisms. Addressing the issue of skin aging is increasingly imperative. Multiple pieces of evidence indicate the potential anti-aging effects of exogenous
nucleotides (NTs) through their ability to inhibit oxidative stress and inflammation. This study aims to investigate whether exogenous NTs can slow down skin aging and elucidate the underlying mechanisms. To achieve this objective, senescence-accelerated mouse prone-8 (SAMP8) mice were utilized and randomly allocated into Aging, NTs-low, NTs-middle, and NTs-high groups, while senescence-accelerated mouse resistant 1 (SAMR1) mice were employed as the control group. After 9 months of NT intervention, dorsal skin samples were collected to analyze the pathology and assess the presence and expression of substances related to the aging process. The findings indicated that a high-dose NT treatment led to a significant increase in the thickness of the epithelium and dermal layers, as well as Hyp content (p < 0.05). Additionally, it was observed that low-dose NT intervention resulted in improved aging, as evidenced by a significant decrease in p16 expression (p < 0.05). Importantly, the administration of high doses of NTs could improve, in some ways, mitochondrial function, which is known to reduce oxidative stress and promote ATP and NAD+ production significantly. These observed effects may be linked to NT-induced autophagy, as evidenced by the decreased expression of p62 and increased expression of LC3BI/II in the intervention groups. Furthermore, NTs were found to upregulate pAMPK and PGC-1α expression while inhibiting the phosphorylation of p38MAPK, JNK, and ERK, suggesting that autophagy may be regulated through the AMPK and MAPK pathways. Therefore, the potential induction of autophagy by NTs may offer benefits in addressing skin aging through the activation of the AMPK pathway and the inhibition of the MAPK pathway.