The mechanisms, hallmarks, and therapies for brain aging and age-related dementia

Age-related cognitive decline and dementia are significant manifestations of brain aging. As the elderly population grows rapidly, the health and socio-economic impacts of cognitive dysfunction have become increasingly significant. Although clinical treatment of dementia has faced considerable challenges over the past few decades, with limited breakthroughs in slowing its progression, there has been substantial progress in understanding the molecular mechanisms and hallmarks of age-related dementia (ARD). This progress brings new hope for the intervention and treatment of this disease. In this review, we categorize the latest findings in ARD biomarkers into four stages based on disease progression: Healthy brain, pre-clinical, mild cognitive impairment, and dementia. We then systematically summarize the most promising therapeutic approaches to prevent or slow ARD at four levels: Genome and epigenome, organelle, cell, and organ and organism. We emphasize the importance of early prevention and detection, along with the implementation of combined treatments as multimodal intervention strategies, to address brain aging and ARD in the future.