Abstract
Metformin is a widely used drug for type 2 diabetes that is considered to have potential anti-aging effects. However, the beneficial effects of metformin in middle-aged normoglycemic mice are less explored. Here, we report that metformin treated by tail vein injection improved cognitive function of aged mice better than oral administration, which seem to show a dose-dependent manner. Correspondingly, long-term oral administration of metformin was associated with significant disability rates. Further, metformin restored cerebral blood flow and brain vascular density and promoted neurogenic potential of the subependymal zone/subventricular zone both in vivo and in vitro. RNA-Seq and q-PCR results indicated that metformin could enhance relative mRNA glycolysis expression in blood and hippocampal tissue, respectively. Mechanistically, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a key enzyme in glycolysis pathway, may contribute to angiogenic and neurogenic potentials of NSCs. Interestingly, the relative GAPDH mRNA expression of peripheral blood mononuclear cell was gradually decreased with aging. Meanwhile its expression level positively correlated with cognitive levels. Our results indicated that metformin represents a candidate pharmacological approach for recruitment of NSCs in aged mouse brain by enhancing glycolysis and promoting neurovascular generation, a strategy that might be of therapeutic value for anti-aging in humans.
Highlights
E, gradually decreased with age, and positively correlated with cognitive levels
Metformin by tail vein injection improved cognitive levels of aged mice As aging is frequently accompanied by cognitive impairments, we examined the effect of metformin administration by tail vein injection on spatial learning and memory of aged mice
Our results show that metformin significantly increased disability rate (Figure 6A), including cancer, cataract, and dermatitis, which is similar to most studies conducted on diabetics showing that long-term treatment with metformin causes a risk of vitamin B-12 deficiency and other side effects in patients with type 2 diabetes [24]
Summary
E, gradually decreased with age, and positively correlated with cognitive levels. Metformin administration enhanced glycolysis through increased mRNA expression of GAPDH, which increased angiogenesis and neurogenic potential of NSCs. Our results indicate that metformin represents a candidate pharmacological approach for recruitment of NSCs in aged mouse brain. Metformin restores neurovascular integrity by enhancing glycolysis, a strategy that might be of therapeutic value for anti-aging in humans
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
