New breakthrough in brain aging research! May be a new dawn for solving Alzheimer's and Parkinson's diseases

As we age, the functions of the human body gradually decline, and the brain is no exception. Recently, a study published in the journal Nature found that multiple cell types in the brains of aged mice underwent significant changes in gene expression, revealing the mystery of brain aging. This article will take you into this study and understand the story behind brain aging.

To gain deeper insights into the mechanisms of brain aging, the researchers performed single-cell transcriptome analysis of young and old mouse brains. Through large-scale, high-quality transcriptome data and detailed cell type annotations, the researchers pinpointed brain regions and cell types that are vulnerable to aging.

The study found that 2,449 genes in the brains of aged mice showed age-related differential expression in specific cell types. These gene expression changes led to the emergence of some transcriptionally unique cell clusters in the aged brain, including microglia, astrocytes, ependymal cells, oligodendrocytes, etc.

Research has found five major characteristics of brain aging:

1. Decreased number of stem cells: Stem cells are special cells that can differentiate into a variety of cell types and help repair and regenerate tissues. When the number of stem cells decreases, the brain's ability to regenerate and repair nerves decreases, which means that as we age, the brain's ability to recover after trauma will weaken.

2. Increased immune response and inflammation: In the aged brain, immune cells, especially microglia, are very likely to malfunction. The main function of these cells is to protect the brain from pathogens, but during the aging process, they become overactive, leading to increased inflammatory responses. Long-term and repeated inflammatory responses can damage brain tissue and affect its normal function.

3. Damage to the neural network structure: Myelin is a layer of material wrapped around the axons of nerve cells, which can increase the speed of nerve signal transmission. In the elderly brain, the formation of myelin is reduced, which reduces the speed of nerve signal transmission, leading to a decline in cognitive function.

4. Nutritional sensing and energy homeostasis disorders: The hypothalamus is a key area for regulating feeding behavior and energy metabolism. Studies have found that certain cell types in the hypothalamus of old mice have significant changes in gene expression compared to certain cell types in young mice. It is speculated that during the aging process, cells in this area begin to show functional abnormalities, leading to loss of appetite and energy metabolism disorders, which in turn affect overall health and brain function.

5. Epigenetic changes: Epigenetics refers to changes in gene expression that do not involve changes in the gene sequence itself, but rather regulate gene activity through other mechanisms. During the aging process, these regulatory mechanisms may become disrupted, leading to abnormal gene expression, which can affect the structure and function of the brain.

Brain aging is a complex biological process that not only directly affects neural function, but is also closely related to the occurrence and development of a variety of neurological diseases.

Alzheimer's disease and Parkinson's disease are two of the most common aging-related neurological diseases. Key changes in the aging brain, such as neuronal loss, synaptic dysfunction, neuroinflammation, and metabolic disorders, are important risk factors for the development of these diseases.

1. Alzheimer's disease: With age, abnormal deposition of amyloid and Tau proteins (microtubule-associated proteins, mainly expressed in neurons of the central nervous system) in the brain forms plaques and tangles, which are the main pathological features of Alzheimer's disease. These lesions disrupt communication between nerve cells, leading to a gradual decline in cognitive function.

2. Parkinson's disease: There are certain special cells in an area of ​​the brain called the substantia nigra that are responsible for producing a chemical called dopamine, which helps us control limb movement. When the number of these cells decreases, the human body may have movement problems such as hand tremors, slow movements, and body stiffness.

In short, the research results of single-cell transcriptome analysis provide new hope for the treatment of brain aging-related diseases, such as Alzheimer's disease, Parkinson's disease, etc. By gaining a deeper understanding of the cellular and molecular mechanisms of brain aging, we hope to develop more effective intervention measures in the future to improve the quality of life of the elderly and reduce the burden on their families and society.

References: Jin K, Yao Z, van Velthoven CTJ, et al.Brain-wide cell-type-specific transcriptomic signatures of healthy aging in mice.[J]. Nature (2025). https://www.nature.com/articles/s41586-024-08350-8