BrainHealth - Decoding life course pathways of mental ageing

“我活得越久，生活就变得越美好。”--弗兰克·劳埃德·赖特在欧洲，65岁的人大约50%的余生都是残疾的。到目前为止，与衰老相关的研究几乎完全集中在衰老的赤字概念上，该概念寻求找到“治疗”而不是通往健康衰老的途径。我将用非传统的方法打破新的界限，即衰老始于出生，需要一种结合了对早期发展、成人精神病学和老年精神衰老的研究的生命过程方法。我的研究项目BrainHealth的愿景是通过在创新的伞形概念下研究精神衰老的生命过程模式，从根本上刻画、改善和区分整个生命周期中的精神衰老。我将扩展和合并来自五个欧洲大型纵向队列的独特数据，这些队列从出生到老年的总样本量超过78,000人，创建全球最全面的大脑健康数据集之一。BrainHealth将包括对大脑年龄、表观遗传年龄、认知功能和精神健康的多模式测量。在一种创新的方法中，我将开发一种新的组织特异性小鼠模型，它是对这些人类数据的补充，将有助于了解机制，加强因果推理，并解决组织特异性。三个工作包将被实施：1)通过建立儿童和青春期大脑健康的稳健预测因子来表征大脑健康；2)通过识别可修改的保护因素来改善大脑健康，以增强整个生命过程中的大脑健康；3)通过开发终身大脑健康的特定组织小鼠模型来区分身体和精神衰老。如果成功，该计划将允许及早识别和改变不健康的衰老轨迹--这是我们时代的一个关键社会挑战--从而彻底改变我们对健康老龄化的方法。

"The longer I live, the more beautiful life becomes." - Frank Lloyd WrightIn Europe, people aged 65 live approximately 50% of their remaining years with disability. Ageing-related research to date has focused almost exclusively on a deficit-concept of ageing, which seeks to find 'cures' instead of pathways towards healthy senescence. I will break new frontiers with the unconventional approach that ageing starts at birth and requires a life course approach that combines research into early development, adult psychiatry, and mental ageing in old age.The vision of my research program BrainHealth is to fundamentally characterise, improve, and differentiate mental ageing across the lifespan by studying the life course patterns of mental ageing under the innovative umbrella concept of 'brain health'. I will expand and combine unique data from five large European longitudinal cohorts with a total sample size of over 78,000 individuals from birth to old age, creating one of the most comprehensive datasets on brain health worldwide. BrainHealth will include multimodal measures of brain age, epigenetic age, cognitive function, and mental well-being. In an innovative approach, I will develop a novel tissue-specific mouse model that is complimentary to these human data and will help to understand mechanisms, strengthen causal inference and address tissue specificity.Three work packages will be implemented to:1) characterise brain health from birth to old age by establishing robust predictors of brain health in childhood and adolescence;2) improve brain health by identifying modifiable protective factors to enhance brain health across the life course;3) differentiate between physical and mental ageing by developing a tissue-specific mouse model of lifelong brain health.If successful, this program will revolutionise our approach to healthy ageing by permitting the early identification and alteration of unhealthy aging trajectories - a key societal challenge of our time.