Saul presents the results of his work in joining the blood systems of young animals to young animals, in which the old animals become younger. These heterchronic parabiosis experiments raise new questions: is it something in young blood that helps the old animals? Or a dilution of the old animals' blood? Will this work in humans? Will it extend lifespan? Many more experiments to try!

1. Young Blood and Brain Aging
Saul Villeda, PhD
University of California San Francisco
Eli and Edythe Stem Cell Institute

2. Aging is a process affecting every individual

3. Aging is associated with a decline in
cognitive functions
Hedden and Gabriel Nat. Rev. Neurosci 2004

4. Aging is associated with a decline in
cognitive functions
Aging
Young Old

5. Question: Can the effects of aging on cognitive
function be reversed?
Aging
Young Old

9. Stem cells and tissue regeneration

10. Stem cells and tissue regeneration

11. Stem cells and tissue regeneration

12. Stem cells and tissue regeneration

13. Stem cells and tissue regeneration

14. Palmer et al. J Comp. Neurol. 2000
Mirzadeh et al. Cell Stem Cell 2008

15. Reviewed by Zhao et al. Cell 2008

16. Reviewed by Zhao et al. Cell 2008

17. Reviewed by Zhao et al. Cell 2008

18. Aging impairs neural stem cells and associated
cognitive function
Reviewed by Lazarov et al.
Trends Neurosci 2010

19. Aging impairs neural stem cells and associated
cognitive function
Reviewed by Lazarov et al.
Trends Neurosci 2010

20. Systemic perturbations in old animals enhances
neural stem cell and cognitive functions
Van Praag et al. J. Neurosci. 2005

21. Systemic perturbations in old animals enhances
neural stem cell and cognitive functions
Van Praag et al. J. Neurosci. 2005

22. Hypothesis
Changes naturally occuring in the aging
systemic milieu (blood) impair neural stem cell
and cognitive functions

23. Using parabiosis surgery to investigate changes in
the young and old brain
Old-Young
Pioneered by Rando Conboy et al. Nature 2005

24. Using parabiosis surgery to investigate changes in
the young and old brain
Young-Young Old-Young Old-Old
Pioneered by Rando Conboy et al. Nature 2005

25. Exposure to old blood impairs neural stem cell
function in young mice
Old Blood
Parabiosis
Villeda et al. Nature 2011

26. Villeda et al. Nature 2011

27. Old = Young
Villeda et al. Nature 2011

28. Exposure to old blood impairs cognitive
function in young mice
Old Blood
Cognitive
Impairments
Parabiosis
Villeda et al. Nature 2011

29. Exposure to young blood enhances neural stem
Stem cells and tissue regeneration
cell function in old animals
Villeda et al. Nature 2011

30. Systemic exposure to young blood enhances
neural stem cell function in old mice
Old = Young
Villeda et al. Nature 2011

31. Systemic exposure to young blood enhances
neural stem cell function in old mice
Old = Young
Villeda et al. Nature 2011

32. Exposure to young blood rejuvenates stem cell
Stem cells and tissue regeneration
function in old animals
Muscle Cells
Young Blood
Neurons
Tissue Specific
Stem Cells
Blood Cells
Conboy et al. Nature 2005, Brack et al. Science 2007, Villeda et al. Nature 2011, Ruckh et al. Cell Stem Cell 2012

33. Question: Can the beneficial effects of young
blood extend beyond stem cell function?
Rejuvenation
?

34. Exposure to young blood improves
communication between neurons in the old brain
Old-Old Old-Young
Rejuvenation

35. Exposure to young blood improves learning
and memory in old animals
Rejuvenation
Cognitive
Improvements

36. Testing hippocampal-dependent spatial
learning and memory
Radial Arm Water Maze DAY 1: Training Phase
DAY 1: Training Phase
Villeda et al. Nature 2011

37. Exposure to young blood improves learning
and memory in old animals

38. Direction of the Lab
Understanding how administration of young blood
late in life improves the old brain
Rejuvenation
Function Genes
Cognition Cells

39. Acknowledgements
Villeda Lab: Collaborators:
 Lucas Smith  Thomas Rando
 Kristopher Plambeck (Stanford/VA Palo Alto)
 Jill Bouchard  Xinmen Xie (AfaSci)
 Liz Wheatley  Bende Zou (AfaSci)
 Marion Buckwalter (Stanford)
Wyss-Coray Lab:  Theo Palmer (Stanford)
 Ge Li (VA Seattle)
 Tony Wyss-Coray  Elaine R. Peskind (VA Seattle)
 Jeong-Soo Park  Jeffrey A. Kaye
 Yingbo He (Oregon Health Sciences)
 Greg Bieri  Joseph F. Quinn
 Jian Luo (Oregon Health Sciences)
 Kira Irving  Douglas R. Galasko (UCSD)
 Rafael Wabhl
 Markus Britschgi
 Alex Eggel Funding:
 Ching Ding
 Trisha Stan  UCSF Fellows (Sandler
 Eva Czirr Foundation)
 Kurt Lucin  NIH Director’s
 Jinte Middledorp Independence Award
 Daniella Birdnik  CIRM Award
 Joseph Castellano  NIA

40. The Villeda Lab at UCSF
COGNITION
AGING
REJUVENATION