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Neuroscience Graduate Program at UCSF

Faculty - Saul Villeda, Ph.D.

Mechanisms of Brain Aging and Rejuvenation

Research Description

Aging alters both the regenerative capacity and functional integrity of the adult brain, and as a result steadily drives cognitive impairments and susceptibility to neurodegenerative disorders in healthy individuals. When considering the rate at which the human population is aging, it becomes imperative to identify means by which to maintain cognitive integrity by protecting against, or even counteracting, the effects of aging. Indeed, the ability to reverse aging in the brain could enable us to sidestep the effects of aging that promote vulnerability to neurodegenerative diseases altogether, providing a unique and unexplored therapeutic approach. Excitingly, we have recently shown that systemic manipulations such as heterochronic parabiosis (in which the circulatory system of an old and young animal are connected) or young plasma administration 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, heterochronic parabiosis studies have revealed an age-dependent bi-directionality in the influence of the systemic environment indicating pro-youthful factors in young blood elicit rejuvenation while pro-aging factors in old blood drive pre-mature aging. Correspondingly, it has been proposed that mitigating the effect of pro-aging factors in old blood may also provide an effective approach to rejuvenate aging phenotypes. These findings promote strategies altering both systemic pro-youthful or pro-aging factors as exciting new approaches for brain rejuvenation. Our lab is interested in understanding what drives regenerative and cognitive impairments in the aging brain, and how the effects of aging can be reversed in the old brain. Ultimately, our goal is to elucidate cellular and molecular mechanisms that promote brain rejuvenation as a means by which to combat age-related neurodegeneration and cognitive dysfunction.

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Current Projects

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Lab Members

Shell Fan, Postdoctoral Fellow
Hank Garcia, Postdoctoral Fellow
Geraldine Gontier, Postdoctoral Fellow
Karin Lin, Graduate Student (NS)
Jeremy Shea, Postdoctoral Fellow
Lucas Smith, Graduate Student (BMS)
Joe Udeochu, Graduate Student (BMS)
Patrick Venture, Lab Manager
Elizabeth Wheatley, Graduate Student (DSCB)
Charles White, Graduate Student (DSCB)

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Selected Publications

S.A. Villeda,  J. Luo, K.I. Mosher, B. Zou, M. Britschgi, G. Bieri, T.M. Stan, N. Fainberg, Z. Ding, A. Eggel, K.M. Lucin, E. Czirr, J-S. Park, S. Doupres-Couillard, L. Aigner, G. Li, E.R. Peskind, J.A. Kaye, J.F. Quinn, D.R. Galasko, X.S. Xie, T.A.Rando, and T. Wyss-Coray. 2011. The aging systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 477(7362):90-4. PMID: 21886162.

S.A. Villeda*, K.E. Plambeck, J. Middeldorp, J.M. Castellano, K.I. Mosher, J. Luo, L.K. Smith, G. Bieri, K. Lin, D. Berdnik, R. Wabl, J. Udeochu, E.G. Wheatley, B. Zou, D. Simmons, X.S. Xie, F. Longo, T. Wyss-Coray*. 2014. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nature Medicine.20(6):659-63. PMID: 24793238. *Co-Corresponding Author

L.K. Smith, Y.B. He, J.S. Park G. Bieri, C. Snethlage, K.L. Lin, G. Gontier, R. Wabl, K. Plambeck, J. Udeochu, A. Eggel, R. Narashima, J. Bouchard, J.L. Grant, J. Lou, T. Wyss-Coray and S.A. Villeda*. 2015. β2-Microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis. Nature Medicine 21(8):932-37. PMID: 26147761 *Corresponding Author.

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Saul Villeda, Ph.D.


Phone 415-502-1929

Office Address

513 Parnassus Avenue
Room 1325, Box 0452
San Francisco, CA 94143

Other Websites

Lab Website

BMS Graduate Program

DSCB Graduate Program