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Removing Senescent Cells in the Brain Reduces Tau Aggregation


Today, we wanted to draw your attention to a recent study showing an association between the accumulation of Tau proteins, which are misfolded proteins that typically indicate Alzheimer’s disease, and senescent cells. The researchers also showed that Tau pathology was improved by the use of drugs that remove non-dividing senescent cells.

Removing senescent cells reduces neurodegeneration

These researchers demonstrate that DNA damage, NF-kB activation, and the SASP, which is a collection of inflammatory signals secreted by senescent cells, are all associated with the presence of Tau‐containing neurofibrillary tangles.

Perhaps the most interesting thing about this paper is that the researchers tested the senolytic drugs dasatinib and quercetin and reported a reduction in Tau‐containing neurofibrillary tangles and neurodegeneration; this was also accompanied by an increase of cerebral blood flow. Dasatinib is an approved cancer drug and Quercetin is a commonly available supplement one can buy over the counter in most countries and is present in many vegetables. It has long been suggested that removing these problem senescent cells could help reduce the age-related decline of tissue regeneration and this is yet another demonstration of this.

Tau protein accumulation is the most common pathology among degenerative brain diseases, including Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), traumatic brain injury (TBI) and over twenty others. Tau‐containing neurofibrillary tangle (NFT) accumulation is the closest correlate with cognitive decline and cell loss (Arriagada et al., 1992), yet mechanisms mediating tau toxicity are poorly understood. NFT formation does not induce apoptosis (de Calignon et al., 2009), which suggests secondary mechanisms are driving toxicity. Transcriptomic analyses of NFT‐containing neurons microdissected from postmortem AD brain revealed an expression profile consistent with cellular senescence. This complex stress response induces aberrant cell cycle activity, adaptations to maintain survival, cellular remodeling, and metabolic dysfunction. Using four AD transgenic mouse models, we found that NFTs, but not Aβ plaques, display a senescence‐like phenotype. Cdkn2a transcript level, a hallmark measure of senescence, directly correlated with brain atrophy and NFT burden in mice. This relationship extended to postmortem brain tissue from humans with PSP to indicate a phenomenon common to tau toxicity. Tau transgenic mice with late stage pathology were treated with senolytics to remove senescent cells. Despite the advanced age and disease progression, MRI brain imaging and histopathological analyses indicated a reduction in total NFT density, neuron loss and ventricular enlargement. Collectively, these findings indicate a strong association between the presence of NFTs and cellular senescence in the brain, which contributes to neurodegeneration. Given the prevalence of tau protein deposition among neurodegenerative diseases, these findings have broad implications for understanding, and potentially treating, dozens of brain diseases.


This is yet more confirmation that the presence of senescent cells is harmful and that their removal appears to be beneficial to health. Senolytics are now in human trials, and the hope is the results in mice will translate to humans; given that senescent cells are a fundamental and common phenomenon in both species, there is every reason to be optimistic.

If you would like to learn more about the progress in senolytics and other therapies against the aging processes, check out the Rejuvenation Roadmap, which gives an overview of all the major aging research projects and their progress.

About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 600 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve is one of three recipients of the 2020 H+ Innovator Award and shares this honour with Mirko Ranieri – Google AR and Dinorah Delfin – Immortalists Magazine. The H+ Innovator Award looks into our community and acknowledges ideas and projects that encourage social change, achieve scientific accomplishments, technological advances, philosophical and intellectual visions, author unique narratives, build fascinating artistic ventures, and develop products that bridge gaps and help us to achieve transhumanist goals. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.
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