Top-Performer: TGF-beta and Oxytocin Reversed to Reverse Aging

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September 21, 2021

Aging-US published this high-scoring research paper on August 15, 2019, entitled, “Rejuvenation of brain, liver and muscle by simultaneous pharmacological modulation of two signaling determinants, that change in opposite directions with age,” by researchers from the Department of Bioengineering and QB3 Institute, University of California, Berkeley, Berkeley, CA; Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA. Abstract: We hypothesize that altered intensities of a few morphogenic pathways account for most/all the phenotypes of aging. Investigating this has revealed a novel approach to rejuvenate multiple mammalian tissues by defined pharmacology. Specifically, we pursued the simultaneous youthful in vivo calibration of two determinants: TGF-beta which activates ALK5/pSmad 2,3 and goes up with age, and oxytocin (OT) which activates MAPK and diminishes with age. The dose of Alk5 inhibitor (Alk5i) was reduced by 10-fold and the duration of treatment was shortened (to minimize overt skewing of cell-signaling pathways), yet the positive outcomes were broadened, as compared with our previous studies. Alk5i plus OT quickly and robustly enhanced neurogenesis, reduced neuro-inflammation, improved cognitive performance, and rejuvenated livers and muscle in old mice. Interestingly, the combination also diminished the numbers of cells that express the CDK inhibitor and marker of senescence p16 in vivo. Summarily, simultaneously re-normalizing two pathways that change with age in opposite ways (up vs. down) synergistically reverses multiple symptoms of aging. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.102148 DOI - https://doi.org/10.18632/aging.102148 Full text - https://www.aging-us.com/article/102148/text Correspondence to: Irina M. Conboy email: iconboy@berkeley.edu Keywords: muscle repair, TGF-beta, oxytocin, neurogenesis, neuro-inflammation, cognition, liver health About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at http://www.Aging-US.com​​ or connect with us on: Twitter - https://twitter.com/AgingJrnl​ Facebook - https://www.facebook.com/AgingUS/​ SoundCloud - https://soundcloud.com/aging-us​ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging​ Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

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