Research Paper Volume 15, Issue 21 pp 11740—11763
1,5-anhydro-D-fructose induces anti-aging effects on aging-associated brain diseases by increasing 5’-adenosine monophosphate-activated protein kinase activity via the peroxisome proliferator-activated receptor-γ co-activator-1α/brain-derived neurotrophic factor pathway
- 1 Division of Brain Science, Department of Physiology, Kurume University School of Medicine, Fukuoka 830-0011, Japan
- 2 Department of Neurosurgery, Kurume University School of Medicine, Fukuoka 830-0011, Japan
- 3 Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan
- 4 Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima 890-8544, Japan
- 5 Division of Laboratory Animal Resources and Research, Center for Advanced Science Research and Promotion, Kagoshima University, Kagoshima 890-8520, Japan
Received: December 5, 2022 Accepted: October 11, 2023 Published: November 9, 2023
https://doi.org/10.18632/aging.205228How to Cite
Copyright: © 2023 Kikuchi et al.. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
5’-Adenosine monophosphate-activated protein kinase (AMPK) is a metabolic sensor that serves as a cellular housekeeper; it also controls energy homeostasis and stress resistance. Thus, correct regulation of this factor can enhance health and survival. AMPK signaling may have a critical role in aging-associated brain diseases. Some in vitro studies have shown that 1,5-anhydro-D-fructose (1,5-AF) induces AMPK activation. In the present study, we experimentally evaluated the effects of 1,5-AF on aging-associated brain diseases in vivo using an animal model of acute ischemic stroke (AIS), stroke-prone spontaneously hypertensive rats (SHRSPs), and the spontaneous senescence-accelerated mouse-prone 8 (SAMP8) model. In the AIS model, intraperitoneal injection of 1,5-AF reduced cerebral infarct volume, neurological deficits, and mortality. In SHRSPs, oral administration of 1,5-AF reduced blood pressure and prolonged survival. In the SAMP8 model, oral administration of 1,5-AF alleviated aging-related decline in motor cognitive function. Although aging reduced the expression levels of peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) and brain-derived neurotrophic factor (BDNF), we found that 1,5-AF activated AMPK, which led to upregulation of the PGC-1α/BDNF pathway. Our results suggest that 1,5-AF can induce endogenous neurovascular protection, potentially preventing aging-associated brain diseases. Clinical studies are needed to determine whether 1,5-AF can prevent aging-associated brain diseases.