Del Re Francesco Maria, Russ David W, Dimova Kalina P, Scordilis Stylianos P
Department of Biological Sciences, Smith College, Northampton, Massachusetts, United States of America.
School of Physical Therapy and Rehabilitation Sciences, University of South Florida, Morsani College of Medicine, Tampa, Florida, United States of America.
PLoS One. 2025 May 27;20(5):e0323602. doi: 10.1371/journal.pone.0323602. eCollection 2025.
Aging is a pan-organ process with an intricate and multimodal nature. Deciphering the aging phenomenon is complex, yet recent attention is analyzing the potential benefits of non-invasive life adjustments to achieve healthy aging. Omega-3 polyunsaturated fatty acids (FA) have emerged as promising nutraceuticals for a plethora of different medical conditions. In the current study we conducted an in-depth, bottom-up, global, shotgun proteomic study (LC-MS/MS) investigating both the effects of aging on skeletal muscle and the potential alterations due to ω-3 FA. Sprague Dawley rats were fed different diets and divided into four groups (n = 5 per group): adult controls (7-8 months, ADCTL); aged controls (22 months, AGCTL); and adult (ADω3) and aged (AGω3) rats fed an ω-3 supplemented diet. Among the identified 30,000 soleus proteins, our proteomic analysis identified 149 proteins differentially expressed in aging; 207 proteins with aging, but fed ω-3 FA; and 105 and 26 proteins, respectively, when aged and adult rats were fed ω-3 FA. Aging alone (ADCTL/AGCTL) affects many processes: carbohydrate and lipid metabolisms, proteostasis, mRNA processing and sarcomeric proteins. With FA supplementation and aging (ADω3/AGω3) similar processes were affected, but increased chromatin-related protein abundances (methylation or histone deacetylation) were observed in AGω3; while proteins involved in OXPHOS and mitochondrial homeostasis, including mTOR, were more represented in ADω3 rats. Supplementation with FA had a greater effect in aged rats (AGCTL/AGω3) than in adult ones (ADCTL/ADω3). In the ADCTL/ADω3 comparison, modest changes were seen, whereas in the AGCTL/AGω3 comparisons DNA damage repair increased and protein synthesis and degradation were observed. Further, a potential link to enhancement of myogenesis is also evident. The data presented in this work suggest potential beneficial and protective effects of ω3 FA supplementation in the soleus muscle, as well as some potential molecular mechanisms of action.
衰老 是一个涉及多个器官的过程,具有复杂和多模式的性质。解读衰老现象很复杂,但最近人们关注的是分析非侵入性生活调整对实现健康衰老的潜在益处。ω-3多不饱和脂肪酸(FA)已成为对多种不同医疗状况有前景的营养保健品。在当前研究中,我们进行了一项深入的、自下而上的、全面的鸟枪法蛋白质组学研究(液相色谱-串联质谱法),调查衰老对骨骼肌的影响以及ω-3 FA引起的潜在变化。将斯普拉格-道利大鼠喂食不同饮食,并分为四组(每组n = 5):成年对照组(7 - 8个月,ADCTL);老年对照组(22个月,AGCTL);以及喂食ω-3补充饮食的成年(ADω3)和老年(AGω3)大鼠。在所鉴定的30,000种比目鱼肌蛋白质中,我们的蛋白质组学分析确定了149种在衰老中差异表达的蛋白质;207种在衰老且喂食ω-3 FA时差异表达的蛋白质;以及分别在老年和成年大鼠喂食ω-3 FA时差异表达的105种和26种蛋白质。仅衰老(ADCTL/AGCTL)就会影响许多过程:碳水化合物和脂质代谢、蛋白质稳态、mRNA加工和肌节蛋白。补充FA并伴随衰老(ADω3/AGω3)时,类似的过程会受到影响,但在AGω3中观察到与染色质相关的蛋白质丰度增加(甲基化或组蛋白去乙酰化);而参与氧化磷酸化和线粒体稳态的蛋白质,包括mTOR,在ADω3大鼠中更具代表性。补充FA对老年大鼠(AGCTL/AGω3)的影响比对成年大鼠(ADCTL/ADω3)更大。在ADCTL/ADω3比较中,观察到适度变化,而在AGCTL/AGω3比较中,DNA损伤修复增加,同时观察到蛋白质合成和降解。此外,与肌生成增强的潜在联系也很明显。这项工作中呈现的数据表明补充ω-3 FA在比目鱼肌中具有潜在的有益和保护作用,以及一些潜在的分子作用机制。