Saul Villeda, PhD

Assistant Professor
Department of Anatomy
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research
+1 415 502-1929
Research Description: 

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.

Primary Thematic Area: 
Secondary Thematic Area: 
Developmental & Stem Cell Biology
Research Summary: 
Mechanisms of Brain Aging and Rejuvenation



Dampening the Power of the Brain-When Aging Meets Cognition.

The journals of gerontology. Series A, Biological sciences and medical sciences

Shea JM, Villeda SA

Age-related loss of neural stem cell O-GlcNAc promotes a glial fate switch through STAT3 activation.

Proceedings of the National Academy of Sciences of the United States of America

White CW, Fan X, Maynard JC, Wheatley EG, Bieri G, Couthouis J, Burlingame AL, Villeda SA

The aged hematopoietic system promotes hippocampal-dependent cognitive decline.

Aging cell

Smith LK, Verovskaya E, Bieri G, Horowitz AM, von Ungern-Sternberg SNI, Lin K, Seizer P, Passegué E, Villeda SA

Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain.

Science (New York, N.Y.)

Horowitz AM, Fan X, Bieri G, Smith LK, Sanchez-Diaz CI, Schroer AB, Gontier G, Casaletto KB, Kramer JH, Williams KE, Villeda SA

Eosinophils regulate adipose tissue inflammation and sustain physical and immunological fitness in old age.

Nature Metabolism

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