한빛사논문
- 조회292
Salman Sadullah Usmani 1,2, Hyun-Gug Jung 1,2, Qichao Zhang 1, Min Woo Kim 1, Yuna Choi 1, Ahmet Burak Caglayan 1 & Dongsheng Cai 1,*
1Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.
2These authors contributed equally: Salman Sadullah Usmani, Hyun-Gug Jung.
*Corresponding author: correspondence to Dongsheng Cai
Abstract
The hypothalamus plays an important role in aging, but it remains unclear regarding the underlying epigenetics and whether this hypothalamic basis can help address aging-related diseases. Here, by comparing mouse hypothalamus with two other limbic system components, we show that the hypothalamus is characterized by distinctively high-level DNA methylation during young age and by the distinct dynamics of DNA methylation and demethylation when approaching middle age. On the other hand, age-related DNA methylation in these limbic system components commonly and sensitively applies to genes in hypothalamic regulatory pathways, notably oxytocin (OXT) and gonadotropin-releasing hormone (GnRH) pathways. Middle age is associated with transcriptional declines of genes which encode OXT, GnRH and signaling components, which similarly occur in an Alzheimer’s disease (AD)-like model. Therapeutically, OXT-GnRH combination is substantially more effective than individual peptides in treating AD-like disorders in male 5×FAD model. In conclusion, the hypothalamus is important for modeling age-related DNA methylation and developing hypothalamic strategies to combat AD.
논문정보
- Research article
- 2024년 10월 (BRIC 등록일 2024-11-02)
- 국외 연구진
- 생명과학 > 신경생물학
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