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Rejuvenation of the aged brain immune cell landscape in mice through p16-positive senescent cell clearance
Xu Zhang 1 2, Vesselina M Pearsall 1, Chase M Carver 3, Elizabeth J Atkinson 4, Benjamin D S Clarkson 5 6, Ethan M Grund 7, Michelle Baez-Faria 3 6, Kevin D Pavelko 8, Jennifer M Kachergus 9, Thomas A White 1, Renee K Johnson 5, Courtney S Malo 8, Alan M Gonzalez-Suarez 3, Katayoun Ayasoufi 8, Kurt O Johnson 1, Zachariah P Tritz 8, Cori E Fain 8, Roman H Khadka 8, Mikolaj Ogrodnik 1 10, Diana Jurk 1 3 5, Yi Zhu 1 3, Tamara Tchkonia 1 3, Alexander Revzin 3, James L Kirkland 1 3 11, Aaron J Johnson 8, Charles L Howe 5 12 13, E Aubrey Thompson 9, Nathan K LeBrasseur 1 2 3, Marissa J Schafer 14 15 16
Abstract:
...We show that senescence and inflammatory expression profiles increase with age and are brain region- and sex-specific. p16-positive myeloid cells exhibiting senescent and disease-associated activation signatures, including upregulation of chemoattractant factors, accumulate in the aged mouse brain. Senescent brain myeloid cells promote peripheral immune cell chemotaxis in vitro. Activated resident and infiltrating immune cells increase in the aged brain and are partially restored to youthful levels through p16-positive senescent cell clearance in female p16-InkAttac mice, which is associated with preservation of cognitive function.
PMID: 36167854
Free Full-Text: https://www.nature.com/articles/s41467-022-33226-8
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