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Saul Villeda, PhD

Title(s)Assistant Professor, Anatomy
SchoolSchool of Medicine
Address513 Parnassus Ave, MSB
San Francisco CA 94117
Phone415-502-1929
ORCID ORCID Icon0000-0002-2726-9582 Additional info
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    Collapse Biography 
    Collapse Education and Training
    Stanford UniversityPh.D.2011Neuroscience
    University of California, Los AngelesB.S.2004Physiological Science
    Collapse Awards and Honors
    2019Endowed Chair in Biomedical Sciences
    2018W.M. Keck Foundation Medical Research Award (Co-PI)
    2015Glenn Award for Research on the Biological Mechanisms of Aging
    2012NIH Director's Early Independence Award (DP5)

    Collapse Overview 
    Collapse Overview
    My lab has previously shown that systemic manipulations such as heterochronic parabiosis (in which the circulatory system of an old and young animal are connected), administration of young blood plasma, or administration of exercise-induced blood factors can partially reverse age-related loss of plasticity in the aged brain. As a consequence, we can now consider reactivating latent plasticity dormant in the aged brain as a means to rejuvenate regenerative, synaptic and cognitive functions late in life. Interestingly, work from my lab has revealed bi-directionality in the influence of the systemic environment indicating pro-youthful factors in young blood or following exercise elicit rejuvenation while pro-aging factors in old blood drive pre-mature aging. Our work has further indicated that mitigating the effect of pro-aging factors in old blood may also provide an effective approach to rejuvenate aging phenotypes. The goal of my research program is to elucidate cellular and molecular mechanisms that can be targeted to halt the aging process or promote rejuvenation in the old brain, as a means to counteract dementia-related neurodegenerative disease in the elderly, providing a unique therapeutic approach.

    Collapse Research 
    Collapse Research Activities and Funding
    Role of exercise-induced blood factors in rejuvenating the aged brain
    NIH/NIA R01AG067740May 1, 2020 - Mar 31, 2025
    Role: Principal Investigator
    Role of O-GlcNAcylation in Regulating Neurodegeneration in Aging and Alzheimer?s Disease
    NIH/NIA RF1AG062357Sep 30, 2018 - Jun 30, 2023
    Role: Principal Investigator
    Investigating the pro-aging role of B2M and MHC molecules on regenerative and cognitive function in the brain
    NIH/NIA R01AG055797Mar 1, 2017 - Feb 28, 2022
    Role: Principal Investigator
    Mechanisms of brain rejuvenation
    NIH/NIA R01AG053382Aug 15, 2016 - Apr 30, 2021
    Role: Principal Investigator
    Regulation of Neurogenesis and Cognition by Systemic Age-Related Immune Factors
    NIH DP5OD012178Sep 15, 2012 - Aug 31, 2017
    Role: Principal Investigator
    Regulation of Neural Stem Cells by Changes in the Aging Systemic Environment
    NIH/NIA F31AG034045Mar 13, 2009 - Sep 12, 2011
    Role: Principal Investigator

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    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help. to make corrections and additions.
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    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Dampening the Power of the Brain-When Aging Meets Cognition. J Gerontol A Biol Sci Med Sci. 2020 Sep 16; 75(9):1607-1608. Shea JM, Villeda SA. PMID: 32936914.
      View in: PubMed   Mentions:    Fields:    
    2. Age-related loss of neural stem cell O-GlcNAc promotes a glial fate switch through STAT3 activation. Proc Natl Acad Sci U S A. 2020 Aug 26. White CW, Fan X, Maynard JC, Wheatley EG, Bieri G, Couthouis J, Burlingame AL, Villeda SA. PMID: 32848054.
      View in: PubMed   Mentions:    Fields:    
    3. Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain. Science. 2020 07 10; 369(6500):167-173. Horowitz AM, Fan X, Bieri G, Smith LK, Sanchez-Diaz CI, Schroer AB, Gontier G, Casaletto KB, Kramer JH, Williams KE, Villeda SA. PMID: 32646997.
      View in: PubMed   Mentions: 3     Fields:    Translation:AnimalsCells
    4. Eosinophils regulate adipose tissue inflammation and sustain physical and immunological fitness in old age. Nat Metab. 2020 Aug; 2(8):688-702. Brigger D, Riether C, van Brummelen R, Mosher KI, Shiu A, Ding Z, Zbären N, Gasser P, Guntern P, Yousef H, Castellano JM, Storni F, Graff-Radford N, Britschgi M, Grandgirard D, Hinterbrandner M, Siegrist M, Moullan N, Hofstetter W, Leib SL, Villiger PM, Auwerx J, Villeda SA, Wyss-Coray T, Noti M, Eggel A. PMID: 32694825.
      View in: PubMed   Mentions:
    5. Tolerance induction and microglial engraftment after fetal therapy without conditioning in mice with Mucopolysaccharidosis type VII. Sci Transl Med. 2020 02 26; 12(532). Nguyen QH, Witt RG, Wang B, Eikani C, Shea J, Smith LK, Boyle G, Cadaoas J, Sper R, MacKenzie JD, Villeda S, MacKenzie TC. PMID: 32102934.
      View in: PubMed   Mentions: 1     Fields:    
    6. OPCs on a Diet: A Youthful Serving of Remyelination. Cell Metab. 2019 12 03; 30(6):1004-1006. White CW, Pratt K, Villeda SA. PMID: 31801054.
      View in: PubMed   Mentions:    Fields:    Translation:Cells
    7. MECHANISMS OF BRAIN REJUVENATION. Innovation in Aging. 2019 Nov 8; 3(Supplement_1):s587-s587. Saul Villeda. .
      View in: Publisher Site   Mentions:
    8. Neuronal O-GlcNAcylation Improves Cognitive Function in the Aged Mouse Brain. Curr Biol. 2019 10 21; 29(20):3359-3369.e4. Wheatley EG, Albarran E, White CW, Bieri G, Sanchez-Diaz C, Pratt K, Snethlage CE, Ding JB, Villeda SA. PMID: 31588002.
      View in: PubMed   Mentions: 2     Fields:    Translation:AnimalsCells
    9. Tissue-Resident Group 2 Innate Lymphoid Cells Differentiate by Layered Ontogeny and In Situ Perinatal Priming. Immunity. 2019 06 18; 50(6):1425-1438.e5. Schneider C, Lee J, Koga S, Ricardo-Gonzalez RR, Nussbaum JC, Smith LK, Villeda SA, Liang HE, Locksley RM. PMID: 31128962.
      View in: PubMed   Mentions: 18     Fields:    Translation:AnimalsCells
    10. Innovative approaches in cognitive aging. Neurobiol Aging. 2019 11; 83:150-154. Austad SN, Wood MA, Villeda SA, Voss JL, Sahay A, Albert M. PMID: 31277894.
      View in: PubMed   Mentions:    Fields:    Translation:HumansAnimals
    11. Platelets Give a Running Start to Adult Hippocampal Neurogenesis. Stem Cell Reports. 2019 04 09; 12(4):643-646. Schroer AB, Horowitz AM, Villeda SA. PMID: 30951653.
      View in: PubMed   Mentions:    Fields:    Translation:HumansAnimalsCells
    12. Fetal enzyme replacement and stem cell transplantation in murine Sly syndrome targeting microglia. Molecular Genetics and Metabolism. 2019 Feb 1; 126(2):s107. Quoc-Hung Nguyen, Russell Witt, Lucas Smith, Jeremy Shea, Bowen Wang, Carlo Eikani, Saul Villeda, Tippi MacKenzie. .
      View in: Publisher Site   Mentions:
    13. MANF regulates metabolic and immune homeostasis in ageing and protects against liver damage. Nat Metab. 2019 Feb; 1(2):276-290. Sousa-Victor P, Neves J, Cedron-Craft W, Ventura PB, Liao CY, Riley RR, Soifer I, van Bruggen N, Kolumam GA, Villeda SA, Lamba DA, Jasper H. PMID: 31489403.
      View in: PubMed   Mentions:
    14. Proteolytic cleavage of Beclin 1 exacerbates neurodegeneration. Mol Neurodegener. 2018 12 29; 13(1):68. Bieri G, Lucin KM, O'Brien CE, Zhang H, Villeda SA, Wyss-Coray T. PMID: 30594228.
      View in: PubMed   Mentions: 1     Fields:    Translation:HumansAnimalsCells
    15. Hematopoietic Stem Cell Transplantation Using a Non-Toxic Regimen to Ablate the Fetal Bone Marrow Niche Enables Engraftment of Brain Microglial Cells. Journal of the American College of Surgeons. 2018 Oct 1; 227(4):s252-s253. Quoc-Hung L. Nguyen, Russell G. Witt, Bowen Wang, Jeremy Shea, Saul Villeda, Tippi C. Mackenzie. .
      View in: Publisher Site   Mentions:
    16. 1021 Origin of type 2 innate lymphoid cells in the skin. Journal of Investigative Dermatology. 2018 May 1; 138(5):s173. J. Lee, C. Schneider, H. Liang, R. Ricardo-Gonzalez, J. Nussbaum, L. Smith, S. Villeda, R. Locksley. .
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    17. Tet2 Rescues Age-Related Regenerative Decline and Enhances Cognitive Function in the Adult Mouse Brain. Cell Rep. 2018 02 20; 22(8):1974-1981. Gontier G, Iyer M, Shea JM, Bieri G, Wheatley EG, Ramalho-Santos M, Villeda SA. PMID: 29466726.
      View in: PubMed   Mentions: 19     Fields:    Translation:AnimalsCells
    18. The systemic environment: at the interface of aging and adult neurogenesis. Cell Tissue Res. 2018 01; 371(1):105-113. Smith LK, White CW, Villeda SA. PMID: 29124393.
      View in: PubMed   Mentions: 10     Fields:    Translation:HumansAnimalsCells
    19. Mef2C restrains microglial inflammatory response and is lost in brain ageing in an IFN-I-dependent manner. Nat Commun. 2017 09 28; 8(1):717. Deczkowska A, Matcovitch-Natan O, Tsitsou-Kampeli A, Ben-Hamo S, Dvir-Szternfeld R, Spinrad A, Singer O, David E, Winter DR, Smith LK, Kertser A, Baruch K, Rosenzweig N, Terem A, Prinz M, Villeda S, Citri A, Amit I, Schwartz M. PMID: 28959042.
      View in: PubMed   Mentions: 17     Fields:    Translation:HumansAnimalsCells
    20. Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease. F1000Res. 2017; 6:1291. Horowitz AM, Villeda SA. PMID: 28815019.
      View in: PubMed   Mentions: 3     Fields:    
    21. Mechanisms of Hippocampal Aging and the Potential for Rejuvenation. Annu Rev Neurosci. 2017 07 25; 40:251-272. Fan X, Wheatley EG, Villeda SA. PMID: 28441118.
      View in: PubMed   Mentions: 18     Fields:    Translation:HumansAnimals
    22. Preclinical Assessment of Young Blood Plasma for Alzheimer Disease. JAMA Neurol. 2016 Nov 01; 73(11):1325-1333. Middeldorp J, Lehallier B, Villeda SA, Miedema SS, Evans E, Czirr E, Zhang H, Luo J, Stan T, Mosher KI, Masliah E, Wyss-Coray T. PMID: 27598869.
      View in: PubMed   Mentions: 31     Fields:    Translation:Animals
    23. Migratory and adhesive cues controlling innate-like lymphocyte surveillance of the pathogen-exposed surface of the lymph node. Elife. 2016 08 03; 5. Zhang Y, Roth TL, Gray EE, Chen H, Rodda LB, Liang Y, Ventura P, Villeda S, Crocker PR, Cyster JG. PMID: 27487469.
      View in: PubMed   Mentions: 18     Fields:    Translation:AnimalsCells
    24. Microglia communication: Parallels between aging and Alzheimer's disease. Clin Exp Neuroimmunol. 2016 May; 7(2):114-125. Udeochu JC, Shea JM, Villeda SA. PMID: 27840659.
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    25. Translational strategies in aging and age-related disease. Nat Med. 2015 Dec; 21(12):1395-9. Armanios M, de Cabo R, Mannick J, Partridge L, van Deursen J, Villeda S. PMID: 26646495.
      View in: PubMed   Mentions: 4     Fields:    Translation:HumansAnimals
    26. Fat Chance for Neural Stem Cells in Alzheimer's Disease. Cell Stem Cell. 2015 Oct 01; 17(4):373-4. Gontier G, Lin K, Villeda SA. PMID: 26431177.
      View in: PubMed   Mentions: 1     Fields:    Translation:AnimalsCells
    27. ß2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis. Nat Med. 2015 Aug; 21(8):932-7. Smith LK, He Y, Park JS, Bieri G, Snethlage CE, Lin K, Gontier G, Wabl R, Plambeck KE, Udeochu J, Wheatley EG, Bouchard J, Eggel A, Narasimha R, Grant JL, Luo J, Wyss-Coray T, Villeda SA. PMID: 26147761.
      View in: PubMed   Mentions: 94     Fields:    Translation:HumansAnimals
    28. Aging and brain rejuvenation as systemic events. J Neurochem. 2015 Jan; 132(1):5-19. Bouchard J, Villeda SA. PMID: 25327899.
      View in: PubMed   Mentions: 15     Fields:    Translation:HumansAnimals
    29. ALK5-dependent TGF-ß signaling is a major determinant of late-stage adult neurogenesis. Nat Neurosci. 2014 Jul; 17(7):943-52. He Y, Zhang H, Yung A, Villeda SA, Jaeger PA, Olayiwola O, Fainberg N, Wyss-Coray T. PMID: 24859199.
      View in: PubMed   Mentions: 36     Fields:    Translation:AnimalsCells
    30. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat Med. 2014 Jun; 20(6):659-63. Villeda SA, Plambeck KE, Middeldorp J, Castellano JM, Mosher KI, Luo J, Smith LK, Bieri G, Lin K, Berdnik D, Wabl R, Udeochu J, Wheatley EG, Zou B, Simmons DA, Xie XS, Longo FM, Wyss-Coray T. PMID: 24793238.
      View in: PubMed   Mentions: 221     Fields:    Translation:AnimalsCells
    31. Long-term cognitive impairments and pathological alterations in a mouse model of repetitive mild traumatic brain injury. Front Neurol. 2014; 5:12. Luo J, Nguyen A, Villeda S, Zhang H, Ding Z, Lindsey D, Bieri G, Castellano JM, Beaupre GS, Wyss-Coray T. PMID: 24550885.
      View in: PubMed   Mentions:
    32. Focused Plasma Proteomics for the Study of Brain Aging and Neurodegeneration. The OMICs. 2013 Dec 1; 183-192. Philipp A. Jaeger, Saul A. Villeda, Daniela Berdnik, Markus Britschgi, Tony-Coray Wyss. .
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    33. Colony-stimulating factor 1 receptor (CSF1R) signaling in injured neurons facilitates protection and survival. J Exp Med. 2013 Jan 14; 210(1):157-72. Luo J, Elwood F, Britschgi M, Villeda S, Zhang H, Ding Z, Zhu L, Alabsi H, Getachew R, Narasimhan R, Wabl R, Fainberg N, James ML, Wong G, Relton J, Gambhir SS, Pollard JW, Wyss-Coray T. PMID: 23296467.
      View in: PubMed   Mentions: 62     Fields:    Translation:HumansAnimalsCells
    34. The circulatory systemic environment as a modulator of neurogenesis and brain aging. Autoimmun Rev. 2013 Apr; 12(6):674-7. Villeda SA, Wyss-Coray T. PMID: 23201925.
      View in: PubMed   Mentions: 23     Fields:    Translation:Animals
    35. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 2011 Aug 31; 477(7362):90-4. Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, Stan TM, Fainberg N, Ding Z, Eggel A, Lucin KM, Czirr E, Park JS, Couillard-Després S, Aigner L, Li G, Peskind ER, Kaye JA, Quinn JF, Galasko DR, Xie XS, Rando TA, Wyss-Coray T. PMID: 21886162.
      View in: PubMed   Mentions: 486     Fields:    Translation:Animals
    36. Complement receptor 2 is expressed in neural progenitor cells and regulates adult hippocampal neurogenesis. J Neurosci. 2011 Mar 16; 31(11):3981-9. Moriyama M, Fukuhara T, Britschgi M, He Y, Narasimhan R, Villeda S, Molina H, Huber BT, Holers M, Wyss-Coray T. PMID: 21411641.
      View in: PubMed   Mentions: 32     Fields:    Translation:AnimalsCells
    37. FoxO3 regulates neural stem cell homeostasis. Cell Stem Cell. 2009 Nov 06; 5(5):527-39. Renault VM, Rafalski VA, Morgan AA, Salih DA, Brett JO, Webb AE, Villeda SA, Thekkat PU, Guillerey C, Denko NC, Palmer TD, Butte AJ, Brunet A. PMID: 19896443.
      View in: PubMed   Mentions: 211     Fields:    Translation:AnimalsCells
    38. Microglia--a wrench in the running wheel? Neuron. 2008 Aug 28; 59(4):527-9. Villeda S, Wyss-Coray T. PMID: 18760689.
      View in: PubMed   Mentions: 5     Fields:    Translation:HumansAnimalsCells
    39. Absence of Reelin results in altered nociception and aberrant neuronal positioning in the dorsal spinal cord. Neuroscience. 2006; 139(4):1385-96. Villeda SA, Akopians AL, Babayan AH, Basbaum AI, Phelps PE. PMID: 16580148.
      View in: PubMed   Mentions: 15     Fields:    Translation:HumansAnimalsCells
    40. Developmental distribution of reelin-positive cells and their secreted product in the rodent spinal cord. J Comp Neurol. 2004 Jan 06; 468(2):165-78. Kubasak MD, Brooks R, Chen S, Villeda SA, Phelps PE. PMID: 14648677.
      View in: PubMed   Mentions: 6     Fields:    Translation:Animals
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