Rejuvenation of regeneration in the aging central nervous system.
Remyelination is a regenerative process in the central nervous system (CNS) that produces new myelin sheaths from adult stem cells. The decline in remyelination that occurs with advancing age poses a significant barrier to therapy in the CNS, particularly for long-term demyelinating diseases such as multiple sclerosis (MS). Here we show that remyelination of experimentally induced demyelination is enhanced in old mice exposed to a youthful systemic milieu through heterochronic parabiosis. Restored remyelination in old animals involves recruitment to the repairing lesions of blood-derived monocytes from the young parabiotic partner, and preventing this recruitment partially inhibits rejuvenation of remyelination. These data suggest that enhanced remyelinating activity requires both youthful monocytes and other factors, and that remyelination-enhancing therapies targeting endogenous cells can be effective throughout life.
MRC Centre for Stem Cell Biology and Regenerative Medicine & Cambridge Centre for Brain Repair & Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
Julia M
JM
Ruckh
Jing-Wei
JW
Zhao
Jennifer L
JL
Shadrach
Peter
P
van Wijngaarden
Tata Nageswara
TN
Rao
Amy J
AJ
Wagers
Robin J M
RJ
Franklin
D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009103:Multiple Sclerosis / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*