The paper delves into the complexities of aging in the brain, a process characterized by the progressive loss of cellular balance, leading to a decline in cognitive abilities and an increased risk of neurodegenerative diseases. As life expectancy rises, understanding the brain aging process becomes crucial for developing therapeutic interventions against age-related neurodegenerative diseases and for enhancing human lifespan and healthspan. The paper first introduces the molecular and cellular hallmarks associated with brain aging, such as genomic instability, loss of proteostasis, and cellular senescence, and their impact on different brain cell populations.

The paper then explores how systemic aging, or aging of the body as a whole, translates into brain aging. It discusses the role of metabolic dysregulation, mitochondrial dysfunction, and stem cell exhaustion in the aging brain. These factors contribute to cognitive decline and neurodegenerative diseases. The paper also highlights the role of cellular senescence, a state of permanent cell cycle arrest, in brain aging. Senescent cells contribute to chronic inflammation, leading to detrimental effects on nearby cells and tissue dysfunction.

Finally, the paper reviews the latest rejuvenating strategies and their impact on the brain. These strategies aim to delay brain aging and related diseases by targeting the molecular mechanisms behind brain aging. The paper concludes by emphasizing the importance of understanding the molecular mechanisms behind brain aging to support the development of strategies to delay aging and prevent or treat age-related neurodegenerative diseases.