Saul Villeda, PhD

Mechanisms of Brain Aging and Rejuvenation

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.

Current Projects

• Investigating the role of systemic blood factors in driving age-related impairments and promoting rejuvenation of adult neurogenesis, synaptic plasticity, and cognitive function.
• Elucidating molecular mechanisms underlying brain aging and rejuvenation at the transcriptional, epigenetic, and post-translation levels.
• Examining the contribution of the innate immune system (microglia) to age-related functional and cognitive impairments

Lab Members

Lab Website