Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines.
Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines.
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DOI：
10.3389/fimmu.2018.00586
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发表时间：
2018
影响因子：
7.3
通讯作者：
Ross OA
中科院分区：
文献类型：
--
作者：
Rea IM;Gibson DS;McGilligan V;McNerlan SE;Alexander HD;Ross OA
细胞因子失调被认为在老年免疫系统的重塑中起着关键作用，有证据表明无法精细控制全身炎症，这似乎是不成功衰老的标志。这种细胞因子表达模式的重塑，具有向促炎表型的渐进趋势，被称为“炎性老化”。尽管有研究，但对大多数与年龄有关的主要疾病（包括动脉粥样硬化、糖尿病、阿尔茨海默病、类风湿性关节炎、癌症和衰老本身）的基础“炎症-衰老”的原因还没有明确的了解。虽然炎症是愈合的正常修复反应的一部分，并且对于保护我们免受细菌和病毒感染以及有害环境因子的影响至关重要，但并非所有炎症都是好的。当炎症变得长期和持续，它可以成为破坏性和破坏性。已经确定了几种与衰老和低度炎症相关的常见分子途径。氧化还原平衡的年龄相关变化，年龄相关衰老细胞的增加，衰老相关分泌表型（SASP）和可触发炎性小体的有效自噬的下降，表明有可能通过抑制促炎分子机制或改善炎症的及时解决来延缓年龄相关疾病和衰老本身。相反，可能会从长寿人群的分子或遗传途径中学习，他们拥有良好的老化质量。在这里，我们将讨论一些目前的想法，并强调分子途径，似乎有助于免疫失衡和细胞因子失调，这是与“炎症”或parainflammation。这些发现的证据将从心血管疾病、癌症、神经炎症和类风湿性关节炎的研究中得出。
Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called “inflamm-aging.” Despite research there is no clear understanding about the causes of “inflamm-aging” that underpin most major age-related diseases, including atherosclerosis, diabetes, Alzheimer’s disease, rheumatoid arthritis, cancer, and aging itself. While inflammation is part of the normal repair response for healing, and essential in keeping us safe from bacterial and viral infections and noxious environmental agents, not all inflammation is good. When inflammation becomes prolonged and persists, it can become damaging and destructive. Several common molecular pathways have been identified that are associated with both aging and low-grade inflammation. The age-related change in redox balance, the increase in age-related senescent cells, the senescence-associated secretory phenotype (SASP) and the decline in effective autophagy that can trigger the inflammasome, suggest that it may be possible to delay age-related diseases and aging itself by suppressing pro-inflammatory molecular mechanisms or improving the timely resolution of inflammation. Conversely there may be learning from molecular or genetic pathways from long-lived cohorts who exemplify good quality aging. Here, we will discuss some of the current ideas and highlight molecular pathways that appear to contribute to the immune imbalance and the cytokine dysregulation, which is associated with “inflammageing” or parainflammation. Evidence of these findings will be drawn from research in cardiovascular disease, cancer, neurological inflammation and rheumatoid arthritis.