Combining growth factors, stem cells, and gene therapy for the aging brain.

Stem cells have been suggested as a possible "fountain of youth" for replacing tissues lost during aging. In the brain, replacing lost neurons is a challenge, as they have to then be reconnected with their appropriate targets. Perhaps a more realistic and practical strategy for affecting the aging process would be to prevent the loss of neurons from occurring, thus retaining intact circuitry. Glial cell line-derived neurotrophic factor (GDNF) can reverse some aspects of aging in the monkey. Additionally, we have recently shown that GDNF directly infused into the human brain has significant effects on the symptoms of Parkinson disease. Human neural stem cells can be cultured, genetically modified, and transplanted. As such, these cells are ideal for ex vivo gene therapy, and may be used in the future as "minipumps" to release GDNF in vivo to protect aging neurons. Using such an approach could delay the effects of aging in the brain, giving a better quality of life. Stem cells might not be the fountain of youth, but provide a fountain of youth through the release of growth factors such as GDNF.