Does Brain Aging Reveal the Hidden Role of Astrocytes in Neurodegenerative Diseases?

With age, the brain undergoes profound transformations that affect memory, speed of thought, and the ability to learn. These changes are not only linked to the loss of neurons but also to the evolution of the cells that surround and support them, particularly astrocytes. Long considered mere supports for neurons, these cells actually play a central role in maintaining brain balance. They regulate energy supply, protect neuronal connections, and help eliminate waste. However, over time, their function deteriorates, directly influencing cognitive decline and vulnerability to diseases such as Alzheimer’s or Parkinson’s.

Astrocytes do not all age in the same way depending on the brain region. In certain areas, such as the hippocampus or the substantia nigra, they lose their ability to support neurons and adopt inflammatory behaviors. Their shape changes, their genetic activity is altered, and they produce substances that can harm neighboring cells. This phenomenon, called senescence, is characterized by the cessation of their ability to divide and the secretion of pro-inflammatory molecules. These senescent astrocytes accumulate with age and disrupt the brain environment, thereby promoting the onset of neurodegenerative disorders.

At the same time, astrocytes can also become reactive in response to injury or imbalances in the brain. This reactivity is not uniform: it varies depending on the type of stress, brain region, and even sex. Some reactive astrocytes release protective factors, while others, on the contrary, worsen damage by activating inflammatory reactions or disrupting communication between neurons. Recent studies show that these reactive and senescent states are not mutually exclusive but can coexist or succeed one another, further complicating the understanding of their impact on aging.

Mitochondria, the powerhouses of cells, play a key role in these transformations. With age, their function deteriorates in astrocytes, reducing their ability to protect neurons and maintain a healthy brain environment. Similarly, the accumulation of misfolded proteins, a hallmark of several neurodegenerative diseases, is worsened by the dysfunction of aging astrocytes.

These findings highlight the importance of better understanding the mechanisms governing astrocyte aging. Rather than seeking to globally block their activity, future therapies could specifically target the signaling pathways or altered functions of these cells. Such an approach would preserve their beneficial role while limiting their harmful effects, thus opening new perspectives in the fight against cognitive decline and age-related diseases.

Attributions and Sources

Origin of the Study

DOI: https://doi.org/10.1007/s11064-026-04709-7

Title: Astrocyte States in Brain Aging and Neurodegeneration: At the Crossroads of Senescence and Reactivity

Journal: Neurochemical Research

Publisher: Springer Science and Business Media LLC

Authors: João Bastos Lima Pacca-Corrêa; Beatriz Martins Fernandes; Michele Siqueira; Raffaela Schafbenker; Gabriela Joras Baumart; Isabella Vivarini Damico; Flávia Carvalho Alcantara Gomes; Isadora Matias