Physical, mental, and cognitive resources are essential for healthy aging. Aging impacts on the structural integrity of various brain regions, including the hippocampus. Even though recent rodent studies hint towards a critical role of the hypothalamus, there is limited evidence on functional consequences of age-related changes of this region in humans. Given its central role in metabolic regulation and affective processing and its connections to the hippocampus, it is plausible that hypothalamic integrity and connectivity are associated with functional age-related decline. We used data of n = 369 participants (18–88 years) from the Cambridge Centre for Ageing and Neuroscience repository to determine functional impacts of potential changes in hypothalamic microstructure across the lifespan. First, we identified age-related changes in microstructure as a function of physical, mental, and cognitive health and compared those findings to changes in hippocampal microstructure. Second, we investigated the relationship of hypothalamic microstructure and resting-state functional connectivity and related those changes to age as well as physical health. Our results showed that hypothalamic microstructure is not affected by depressive symptoms (mental health), cognitive performance (cognitive health), and comparatively stable across the lifespan, but affected by body mass (physical health). Furthermore, body mass changes connectivity to limbic regions including the hippocampus, amygdala, and nucleus accumbens, suggesting functional alterations in the metabolic and reward systems. Our results demonstrate that hypothalamic structure and function are affected by body mass, focused on neural density and dispersion, but not inflammation. Still, observed effect sizes were small, encouraging detailed investigations of individual hypothalamic subunits.

身体、心理和认知资源对于健康老龄化至关重要。衰老会影响包括海马体在内的各个大脑区域的结构完整性。尽管最近的啮齿动物研究暗示了下丘脑的关键作用，但关于人类该区域与年龄相关的变化的功能后果的证据有限。鉴于其在代谢调节和情感处理中的核心作用及其与海马体的联系，下丘脑的完整性和连通性可能与年龄相关的功能衰退有关。我们使用了n的数据 = 369 名来自剑桥老龄化和神经科学中心的参与者（18-88 岁），以确定下丘脑微结构在整个生命周期中潜在变化的功能影响。首先，我们将与年龄相关的微观结构变化确定为身体、心理和认知健康的函数，并将这些发现与海马微观结构的变化进行比较。其次，我们研究了下丘脑微观结构与静息状态功能连接的关系，并将这些变化与年龄和身体健康相关联。我们的研究结果表明，下丘脑微观结构不受抑郁症状（心理健康）、认知表现（认知健康）的影响，并且在整个生命周期中相对稳定，但受体重（身体健康）影响。此外，体重改变了与边缘区域（包括海马体、杏仁核和伏隔核）的连接性，表明代谢和奖励系统的功能发生了变化。我们的研究结果表明，下丘脑结构和功能受体重影响，主要集中在神经密度和分散度上，而不是炎症。尽管如此，观察到的效应量仍然很小，鼓励对单个下丘脑亚基进行详细研究。