Metabolic dysfunction in human skin: Restoration of mitochondrial integrity and metabolic output by nicotinamide (niacinamide) in primary dermal fibroblasts from older aged donors,Aging Cell

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Metabolic dysfunction in human skin: Restoration of mitochondrial integrity and metabolic output by nicotinamide (niacinamide) in primary dermal fibroblasts from older aged donors
Aging Cell ( IF 8.0 ) Pub Date : 2020-09-29 , DOI: 10.1111/acel.13248
John E Oblong ₁ , Amy Bowman ₂ , Holly A Rovito ₁ , Bradley B Jarrold ₁ , Joseph D Sherrill ₁ , Markaisa R Black ₁ , Glyn Nelson ₃ , Alexa B Kimball ₄ , Mark A Birch-Machin ₂

Affiliation

Alterations in metabolism in skin are accelerated by environmental stressors such as solar radiation, leading to premature aging. The impact of aging on mitochondria is of interest given their critical role for metabolic output and the finding that environmental stressors cause lowered energy output, particularly in fibroblasts where damage accumulates. To better understand these metabolic changes with aging, we performed an in‐depth profiling of the expression patterns of dermal genes in face, forearm, and buttock biopsies from females of 20–70 years of age that encode for all subunits comprising complexes I‐V of the mitochondrial electron transport chain. This complements previous preliminary analyses of these changes. “Oxidative phosphorylation” was the top canonical pathway associated with aging in the face, and genes encoding for numerous subunits had decreased expression patterns with age. Investigations on fibroblasts from older aged donors also showed decreased gene expression of numerous subunits from complexes I‐V, oxidative phosphorylation rates, spare respiratory capacity, and mitochondrial number and membrane potential compared to younger cells. Treatment of older fibroblasts with nicotinamide (Nam) restored these measures to younger cell levels. Nam increased complexes I, IV, and V activity and gene expression of representative subunits. Elevated mt‐Keima staining suggests a possible mechanism of action for these restorative effects via mitophagy. Nam also improved mitochondrial number and membrane potential in younger fibroblasts. These findings show there are significant changes in mitochondrial functionality with aging and that Nam treatment can restore bioenergetic efficiency and capacity in older fibroblasts with an amplifying effect in younger cells.

中文翻译：

人体皮肤代谢功能障碍：烟酰胺（烟酰胺）恢复老年供体原代真皮成纤维细胞中的线粒体完整性和代谢输出

太阳辐射等环境压力会加速皮肤新陈代谢的变化，导致过早衰老。衰老对线粒体的影响引起人们的兴趣，因为线粒体对代谢输出至关重要，并且发现环境压力因素会导致能量输出降低，特别是在损伤累积的成纤维细胞中。为了更好地了解这些随年龄增长的代谢变化，我们对 20-70 岁女性面部、前臂和臀部活检中真皮基因的表达模式进行了深入分析，这些基因编码包含复合物 I-V 的所有亚基线粒体电子传递链。这补充了之前对这些变化的初步分析。 “氧化磷酸化”是与面部衰老相关的最典型途径，编码众多亚基的基因的表达模式随着年龄的增长而降低。对老年供体成纤维细胞的研究还表明，与年轻细胞相比，复合物 I-V 的许多亚基的基因表达、氧化磷酸化率、备用呼吸能力、线粒体数量和膜电位均降低。用烟酰胺 (Nam) 治疗老年成纤维细胞可将这些指标恢复到年轻细胞水平。 Nam 增加了复合物 I、IV 和 V 的活性以及代表性亚基的基因表达。 mt-Keima 染色升高表明这些恢复作用可能通过线粒体自噬发挥作用。 Nam 还改善了年轻成纤维细胞的线粒体数量和膜电位。这些发现表明，随着衰老，线粒体功能发生显着变化，Nam 治疗可以恢复老年成纤维细胞的生物能效率和能力，并在年轻细胞中产生放大效应。

更新日期：2020-10-23

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