BrainHealth - Decoding life course pathways of mental ageing

“我活得越久，生活变得越美好。”-弗兰克·劳埃德·赖特在欧洲，65岁的人大约有50%的余生是残疾的。到目前为止，与衰老相关的研究几乎完全集中在衰老的缺陷概念上，它试图找到“治疗方法”，而不是通往健康衰老的途径。我将用一种非传统的方法来突破新领域，即衰老从出生开始，需要一种结合早期发展、成人精神病学和老年心理衰老研究的生命历程方法。我的研究项目“大脑健康”的愿景是在创新的“大脑健康”概念下，通过研究智力衰老的生命历程模式，从根本上描述、改善和区分整个生命周期的智力衰老。我将扩展并结合来自五个大型欧洲纵向队列的独特数据，总样本规模超过78,000人，从出生到老年，创建世界上最全面的大脑健康数据集之一。大脑健康将包括对大脑年龄、表观遗传年龄、认知功能和心理健康的多模式测量。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，与这些人类数据互补，并有助于理解机制，加强因果推理和解决组织特异性问题。将实施三个工作包，以：1)通过建立儿童和青少年大脑健康的可靠预测指标，确定从出生到老年的大脑健康特征；2)通过识别可改变的保护因素来改善大脑健康，从而在整个生命过程中增强大脑健康；3)通过建立一个组织特异性的终身大脑健康小鼠模型来区分身体和精神衰老。如果成功，这一项目将通过允许早期识别和改变不健康的老龄化轨迹（我们这个时代的一个关键社会挑战），彻底改变我们健康老龄化的方法。

"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.