The hypothalamus is known to play an important role in aging, but whether peptides secreted by the hypothalamus might be useful against Alzheimer’s and other aging-related diseases hasn’t been clear. 

In a paper published online on October 31 in Nature Communications, Dongsheng Cai, M.D., Ph.D., and colleagues addressed this question by looking at methylation of DNA—an epigenetic event that  can regulate genes and is associated with aging. After comparing DNA methylation of the hypothalamus versus two other relevant brain regions in young mice, they found that methylation occurred at much higher levels in the hypothalamus. However, this “advantage” in DNA methylation in the hypothalamus was diminished or lost by the time mice reached middle age. Using the epigenetic information obtained from the young mice, the authors found that genes encoding the hypothalamic peptides oxytocin and gonadotropin-releasing hormone (GnRH) were highly affected by methylation—and that levels of both peptides decline not only with aging but also in an Alzheimer’s disease-like mouse model. They therefore conducted a therapeutic study in which they nasally administered oxytocin and GnRH peptides to Alzheimer’s disease-like model mice. The peptide combination effectively treated Alzheimer’s disease-related pathology and neurodegeneration in the animals, while the effects of individual peptides were only modest. The findings suggest that the hypothalamus is important for understanding the role that DNA methylation plays in aging, and they reveal a potential new strategy for treating Alzheimer’s disease. 

Dr. Cai is professor of molecular pharmacology, the Young Men's Division Chair in Physiology and director of the Institute for Neuroimmunology and Inflammation at Einstein. Dr. Cai is a member of Einstein’s Institute for Aging Research, the Einstein-Mount Sinai Diabetes Research Center, and the National Cancer Institute-designated Montefiore Einstein Comprehensive Cancer Center.

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