红细胞中的抗衰老蛋白有助于防止认知衰退

Qiang等人进行的研究发现，红细胞中的一种蛋白质与年龄相关的认知能力下降之间存在联系。

该研究于 2021 年 6 月 17 日发表在开放获取期刊 PLOS Biology上，表明耗尽小鼠血液中的蛋白质 ADORA2B 会导致记忆力下降更快、听觉处理延迟以及大脑炎症加剧。

随着世界各地预期寿命的增加，出现与年龄相关的认知能力下降的人数也在增加。由于血液中的氧气量也会随着年龄的增长而下降，因此该团队假设，腺苷受体 A2B (ADORA2B) 可能会自然地阻止大脑中的衰老，ADORA2B 是红细胞膜上的一种蛋白质，已知有助于释放来自血细胞的氧气，所以它可以被身体使用。为了测试这个想法，他们创造了血液中缺乏 ADORA2B 的小鼠，并将行为和生理指标与对照小鼠进行了比较。

研究小组发现，随着小鼠年龄的增长，缺乏 ADORA2B 的小鼠认知能力下降的标志——记忆力差、听力缺陷和大脑炎症反应——都比对照小鼠更大。此外，在经历一段时间的缺氧后，对没有 ADORA2B 的幼鼠的行为和生理影响远大于对正常幼鼠的影响。

ADORA2B 可以自然地减少大脑衰老，这有助于在需要时为大脑提供氧气。

因此，ADORA2B 可以自然地减少大脑衰老，这有助于在需要时为大脑提供氧气。需要进一步的测试来确定 ADORA2B 水平是否会随着年龄的增长而自然下降，以及用激活 ADORA2B 的药物治疗是否可以减少正常小鼠的认知能力下降。

该研究的负责人夏博士评论说：“红细胞具有不可替代的功能，可以输送氧气以维持我们体内每个细胞的生物能量。然而，它们在与年龄相关的认知和听力功能中的功能在很大程度上仍然未知。我们的研究结果表明，红细胞 ADORA2B 信号级联通过促进小鼠的氧气输送来对抗与年龄相关的认知、记忆和听力衰退的早期发作，并立即突出多个新的恢复活力的目标。”

Original Research:
“Erythrocyte adenosine A2B receptor prevents cognitive and auditory dysfunction by promoting hypoxic and metabolic reprogramming” by Yang Xia et al. PLOS Biology

Abstract

Hypoxia drives aging and promotes age-related cognition and hearing functional decline. Despite the role of erythrocytes in oxygen (O2) transport, their role in the onset of aging and age-related cognitive decline and hearing loss (HL) remains undetermined. Recent studies revealed that signaling through the erythrocyte adenosine A2B receptor (ADORA2B) promotes O2 release to counteract hypoxia at high altitude. However, nothing is known about a role for erythrocyte ADORA2B in age-related functional decline.

Here, we report that loss of murine erythrocyte–specific ADORA2B (eAdora2b−/−) accelerates early onset of age-related impairments in spatial learning, memory, and hearing ability. eAdora2b-/- mice display the early aging-like cellular and molecular features including the proliferation and activation of microglia and macrophages, elevation of pro-inflammatory cytokines, and attenuation of hypoxia-induced glycolytic gene expression to counteract hypoxia in the hippocampus (HIP), cortex, or cochlea. Hypoxia sufficiently accelerates early onset of cognitive and cochlear functional decline and inflammatory response in eAdora2b−/− mice.

Mechanistically, erythrocyte ADORA2B-mediated activation of AMP-activated protein kinase (AMPK) and bisphosphoglycerate mutase (BPGM) promotes hypoxic and metabolic reprogramming to enhance production of 2,3-bisphosphoglycerate (2,3-BPG), an erythrocyte-specific metabolite triggering O2 delivery. Significantly, this finding led us to further discover that murine erythroblast ADORA2B and BPGM mRNA levels and erythrocyte BPGM activity are reduced during normal aging.

Overall, we determined that erythrocyte ADORA2B–BPGM axis is a key component for anti-aging and anti-age–related functional decline.