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Male F344 rats were treated from 12 to 18\u2009months of age with D\u2009+\u2009Q, ABT\u2010263, or vehicle, and were compared to young (6\u00a0months). Both senolytic treatments rescued memory, preserved the blood\u2013brain barrier (BBB) integrity, and prevented the age\u2010related decline in hippocampal N\u2010methyl\u2010D\u2010aspartate receptor (NMDAR) function associated with impaired cognition. Senolytic treatments decreased senescence\u2010associated secretory phenotype (SASP) and inflammatory cytokines\/chemokines in the plasma (IL\u20101\u03b2, IP\u201010, and RANTES), with some markers more responsive to D\u2009+\u2009Q (TNF\u03b1) or ABT\u2010263 (IFN\u03b3, leptin, EGF). ABT\u2010263 was more effective in decreasing senescence genes in the spleen. Both senolytic treatments decreased the expression of immune response and oxidative stress genes and increased the expression of synaptic genes in the dentate gyrus (DG). However, D\u2009+\u2009Q influenced twice as many genes as ABT\u2010263. Relative to D\u2009+\u2009Q, the ABT\u2010263 group exhibited increased expression of DG genes linked to cell death and negative regulation of apoptosis and microglial cell activation. Furthermore, D\u2009+\u2009Q was more effective at decreasing morphological markers of microglial activation. The results indicate that preserved cognition was associated with the removal of peripheral senescent cells, decreasing systemic inflammation that normally drives neuroinflammation, BBB breakdown, and impaired synaptic function. Dissimilarities associated with brain transcription indicate divergence in central mechanisms, possibly due to differential access.<\/jats:p>","DOI":"10.1111\/acel.13817","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T00:34:25Z","timestamp":1679618065000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Effect of peripheral cellular senescence on brain aging and cognitive decline"],"prefix":"10.1111","volume":"22","author":[{"given":"Vivekananda","family":"Budamagunta","sequence":"first","affiliation":[{"name":"Department of Neuroscience, McKnight Brain Institute University of Florida  Gainesville Florida USA"},{"name":"Genetics and Genomics Graduate Program, Genetics Institute University of Florida  Gainesville Florida USA"},{"name":"Department of Pharmacodynamics, College of Pharmacy University of Florida  Gainesville Florida 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