The document discusses various circulatory factors that influence brain aging, including harmful factors such as eotaxin and beta2-microglobulin, as well as rejuvenating factors like insulin-like growth factor and growth hormone releasing hormone. It references multiple studies highlighting these factors' roles in neurodegeneration and brain health. Overall, it emphasizes the complex interplay between these proteins and brain aging processes.

4. Circulatory Factors with effects on brain aging
Aging or deleterious factors
• Eotaxin/CCL11 (Villeda et al., Nature 2011)
• Beta2-microglobulin/b2M (Smith et al., Nat Medicine 2015)
Rejuvenating or beneficial factors
• Insulin-like growth factor/IGF1 (Trejo et al., JNS 2001)
• IGF2 (Stern et al. Psychoneuroimm. 2014)
• Growth hormone releasing hormone/GHRH (Baker et al., Arch
Neurol., 2012) *
• Gonadotropin releasing hormone/GnRH (Zhang, Nature 2013)
• Growth and differentiation factor 11/GDF11 (Wagers, Lee &
Rubin, Cell 2013, Science 2014)
• Colony stimulating factor 2/CSF2, Tissue inhibitor of
metalloproteinases 2/TIMP2 (Castellano, Nature 2017)
Proteins with indicated effects on healthy brain after
systemic administration in rodents or *humans

5. Aging, neurodegeneration and brain rejuvenation
Wyss-Coray, Nature 2016