Haematopoietic ageing is marked by a loss of regenerative capacity and skewed differentiation from haematopoietic stem cells (HSCs), leading to impaired blood production. Signals from the bone marrow niche tailor blood production, but the contribution of the old niche to haematopoietic ageing remains unclear. Here we characterize the inflammatory milieu that drives both niche and haematopoietic remodelling. We find decreased numbers and functionality of osteoprogenitors at the endosteum and expansion of central marrow LepR⁺ mesenchymal stromal cells associated with deterioration of the sinusoidal vasculature. Together, they create a degraded and inflamed old bone marrow niche. Niche inflammation in turn drives the chronic activation of emergency myelopoiesis pathways in old HSCs and multipotent progenitors, which promotes myeloid differentiation and hinders haematopoietic regeneration. Moreover, we show how production of interleukin-1β (IL-1β) by the damaged endosteum acts in trans to drive the proinflammatory nature of the central marrow, with damaging consequences for the old blood system. Notably, niche deterioration, HSC dysfunction and defective regeneration can all be ameliorated by blocking IL-1 signalling. Our results demonstrate that targeting IL-1 as a key mediator of niche inflammation is a tractable strategy to improve blood production during ageing.

造血衰老的特点是再生能力丧失和造血干细胞 (HSC) 分化失常，导致血液生成受损。来自骨髓生态位的信号调节血液的产生，但旧生态位对造血衰老的贡献仍不清楚。在这里，我们描述了驱动生态位和造血重塑的炎症环境。我们发现骨内膜骨祖细胞的数量和功能减少以及中央骨髓 LepR ⁺间充质基质细胞的扩张与正弦脉管系统的恶化相关。它们共同创造了一个退化和发炎的旧骨髓生态位。生态位炎症反过来驱动老HSC和多能祖细胞中紧急骨髓生成途径的慢性激活，从而促进骨髓分化并阻碍造血再生。此外，我们还展示了受损的骨内膜产生的白细胞介素-1β (IL-1β) 如何反式作用，驱动中央骨髓的促炎性质，对旧血液系统造成破坏性后果。值得注意的是，生态位恶化、HSC 功能障碍和再生缺陷都可以通过阻断 IL-1 信号传导来改善。我们的结果表明，将 IL-1 作为微环境炎症的关键介质，是改善衰老过程中血液生成的一种易于处理的策略。