Differences in the post-stroke innate immune response between young and old.
Differences in the post-stroke innate immune response between young and old.
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DOI：
10.1007/s00281-023-00990-8
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发表时间：
2023-05
影响因子：
9
通讯作者：
Planas, Anna M.
中科院分区：
文献类型：
--
作者：
Gallizioli, Mattia;Arbaizar-Rovirosa, Maria;Brea, David;Planas, Anna M.
衰老与损害基本细胞和组织功能的渐进性变化以及它们之间通过血管和免疫系统的关系有关。衰老因素是理解卒中病理生理学的关键，因为它们增加了卒中的风险并使其功能结局恶化。大多数目前公认的衰老特征也与脑卒中反应有关。值得注意的是，年龄相关的慢性低度炎症与I型干扰素诱导的先天免疫反应有关。干扰素程序在小胶质细胞中是突出的，其中它将细胞损伤、危险信号和吞噬作用与免疫代谢紊乱和炎症相互关联。小胶质细胞吞噬受损的髓鞘和细胞碎片可能压倒细胞清除废物的能力，诱导细胞内脂质积聚。急性炎症和干扰素刺激的基因表达也是急性中风的典型特征，其中小胶质细胞的危险信号识别触发由脂滴生物发生强调的免疫代谢改变。衰老降低了控制这些反应的能力，导致炎症增加和持续，代谢失调和细胞废物处理受损。反过来，衰老过程中的慢性外周炎症诱导免疫衰老，进一步恶化中风诱导的免疫抑制，从而增加中风后感染的风险。衰老还改变了肠道微生物群组成，诱导生态失调。这些变化被年龄相关疾病所增强，如动脉粥样硬化和II型糖尿病，进一步促进血管老化，易患中风，并加剧中风后的大脑炎症。目前衰老研究的进展表明，一些与年龄相关的改变可能会逆转。未来的工作将揭示这种不断发展的抗衰老研究是否可以设计策略来改善老年人的中风结局。
Aging is associated to progressive changes impairing fundamental cellular and tissue functions, and the relationships amongst them through the vascular and immune systems. Aging factors are key to understanding the pathophysiology of stroke since they increase its risk and worsen its functional outcome. Most currently recognised hallmarks of aging are also involved in the cerebral responses to stroke. Notably, age-associated chronic low-grade inflammation is related to innate immune responses highlighted by induction of type-I interferon. The interferon program is prominent in microglia where it interrelates cell damage, danger signals, and phagocytosis with immunometabolic disturbances and inflammation. Microglia engulfment of damaged myelin and cell debris may overwhelm the cellular capacity for waste removal inducing intracellular lipid accumulation. Acute inflammation and interferon-stimulated gene expression are also typical features of acute stroke, where danger signal recognition by microglia trigger immunometabolic alterations underscored by lipid droplet biogenesis. Aging reduces the capacity to control these responses causing increased and persistent inflammation, metabolic dysregulation, and impaired cellular waste disposal. In turn, chronic peripheral inflammation during aging induces immunosenescence further worsening stroke-induced immunodepression, thus increasing the risk of post-stroke infection. Aging also alters gut microbiota composition inducing dysbiosis. These changes are enhanced by age-related diseases, such as atherosclerosis and type-II diabetes, that further promote vascular aging, predispose to stroke, and exacerbate brain inflammation after stroke. Current advances in aging research suggest that some age-associated alterations may be reversed. Future work will unravel whether such evolving anti-aging research may enable designing strategies to improve stroke outcome in the elderly.
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影响因子：
4
作者：
Campisi, Judith
通讯作者：
Campisi, Judith
影响因子：
82.9
作者：
Benakis C;Brea D;Caballero S;Faraco G;Moore J;Murphy M;Sita G;Racchumi G;Ling L;Pamer EG;Iadecola C;Anrather J
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影响因子：
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作者：
Androvic, Peter;Kirdajova, Denisa;Valihrach, Lukas
通讯作者：
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DOI：
10.1038/s43587-021-00093-9
发表时间：
2021-08-01
期刊：
NATURE AGING
影响因子：
--
作者：
Boehme, Marcus;Guzzetta, Katherine E.;Cryan, John F.
通讯作者：
Cryan, John F.
影响因子：
64.8
作者：
Claesson, Marcus J.;Jeffery, Ian B.;O'Toole, Paul W.
通讯作者：
O'Toole, Paul W.