Can Senolytic Therapy Slow Age-Related Spinal Disc Degeneration? Mouse Study | Aging

Aging #Published a new #Research Paper on July 13, 2026, in Volume 18, titled “Slowing intervertebral disc aging in mice through long-term systemic treatment with the senolytic BCL-2/BCL-xL proteolysis targeting chimera (PROTAC) 753b,” by #Researchers from the Ferguson Laboratory for Spine Research, Department of Orthopaedic Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA; The Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL; The Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX; Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL; Masonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN; The Department of Physical Medicine and Rehabilitation, School of Medicine, University of Pittsburgh, Pittsburgh, PA. @pittofficial #Aging #Senolytics #CellularSenescence #SpineHealth #OpenAccess #PeerReviewed #Publishing #MedEd DOI - https://doi.org/10.18632/aging.206394 Corresponding author - Nam Viet Vo - nvv1@pitt.edu Abstract The senolytic PROTAC (753b) eliminates senescent cells (SnCs) by targeting ubiquitin-mediated destruction of the anti-apoptotic BCL-2/BCL-xL proteins. Here, systemic treatment with 753b was tested for reduction of age-related intervertebral disc degeneration (IDD) in mice. Five aging male and female mice were intraperitoneally injected with 753b or vehicle between 16 and 22 months of age. Among vehicle controls, intervertebral disc (IVD) histology using Safranin-O/Fast Green staining of paraffin embedded transverse sections revealed significantly greater IDD in 22m old males than age-matched females. In 22-month-old males, 753b treatment significantly reduced matrix metalloproteinase (MMP)-mediated aggrecan proteolysis as shown by Western blots, loss of disc matrix aggrecan by immunohistochemistry, age-related histomorphologic features of IDD, and serum protein levels of IL-6 and TNFα protein in treated male mice. While expression of IVD cellular senescence markers IL-6, IL-8, TNFα and p16INK4a assessed by RT-PCR of IVD tissue increased with age in both 22m old female and male mice, expression of these markers was not reduced by 753b treatment. These results demonstrate that 753b treatment of aging mice reduced IDD in males but not females, which suggests sex-based differences in the role of senescence in IDD and may have an impact on the potential for females to benefit from anti-senescent therapies for IDD. The observed therapeutic effects of 753b on IVDs of the male mice suggest a global reduction of cellular senescence burden through systemic, non-cell autonomous processes. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206394 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, intervertebral disc aging, cellular senescence, senolytic, anti-apoptosis, PROTAC-753b To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM