Nmnat is a stress response protein which has been involved in a variety of biological processes. However, the effects of Nmnat on aging have not yet been investigated. The present study revealed the effects of Nmnat on aging of Drosophila and uncovered its underlying mechanism. Therefore, the overexpression of Nmnat was established by arm/Gal4 system in Drosophila with an aim to determine the functions of Nmnat during aging process. In this study, our results showed Nmnat was a positive factor on lifespan and movement capacity, which was consistent on d-galactose induced aging acceleration. Further investigation showed that oxidative stress biomarkers, longevity gene, mitochondria related genes and ATP levels were significantly improved in the Nmnat overexpression Drosophila, which suggested that the underlying mechanism of Nmnat on aging process and movement capacity was partly due to its anti-oxidative stress and mitochondrial-protection function. In addition, on HO challenge tests, Nmnat overexpression was sufficient to increase the survival time and movement capacity of Drosophila, which was probably due to its protection against oxidative stress. On rotenone induced mitochondrial dysfunction, Nmnat overexpression also showed better health span and movement capacity than the control group. Based on these data, Nmnat may be a new molecular target to improve health span by enhancing stress resistance and locomotor activity in aging process.
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http://dx.doi.org/10.1016/j.exger.2018.04.026 | DOI Listing |
Neurosci Res
December 2023
John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Robinson Way, CB2 0PY Cambridge, UK. Electronic address:
The past 20 years of research on axon degeneration has revealed fine details on how NAD biology controls axonal survival. Extensive data demonstrate that the NAD precursor NMN binds to and activates the pro-degenerative enzyme SARM1, so a failure to convert sufficient NMN into NAD leads to toxic NMN accumulation and axon degeneration. This involvement of NMN brings the axon degeneration field to an unexpected overlap with research into ageing and extending healthy lifespan.
View Article and Find Full Text PDFFront Aging Neurosci
March 2022
Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States.
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by irreversible cognitive decline with limited therapeutic approaches. We characterized a model of amyloid pathology that expresses human amyloid-beta precursor protein (APP) and β-site APP cleaving enzyme (BACE) in the nervous system. Our model recapitulates the age-dependent accumulation of BACE-derived C-terminal fragment (CTF) and amyloid plaques in the brain, one of the key pathological hallmarks of AD.
View Article and Find Full Text PDFJ Biol Chem
May 2022
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China. Electronic address:
Molecular chaperones safeguard cellular protein homeostasis and obviate proteotoxicity. In the process of aging, as chaperone networks decline, aberrant protein amyloid aggregation accumulates in a mechanism that underpins neurodegeneration, leading to pathologies such as Alzheimer's disease and Parkinson's disease. Thus, it is important to identify and characterize chaperones for preventing such protein aggregation.
View Article and Find Full Text PDFFront Physiol
September 2021
Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China.
Chronic kidney disease (CKD) is a global public health problem with high morbidity and mortality. Decreased nicotinamide adenine dinucleotide (NAD) levels were found to be associated with aging, cancer, and neurodegenerative and metabolic disorders. However, the alteration of renal NAD levels and biosynthesis pathways in CKD is less known.
View Article and Find Full Text PDFJ Exp Biol
September 2021
Ludong University, City Yantai 264025, Shandong Province, China.
Endurance exercise is an important way to resist and treat high-fat diet (HFD)-induced lipotoxic cardiomyopathy, but the underlying molecular mechanisms are poorly understood. Here, we used Drosophila to identify whether cardiac Nmnat/NAD+/SIR2 pathway activation mediates endurance exercise-induced resistance to lipotoxic cardiomyopathy. The results showed that endurance exercise activated the cardiac Nmnat/NAD+/SIR2/FOXO pathway and the Nmnat/NAD+/SIR2/PGC-1α pathway, including up-regulating cardiac Nmnat, SIR2, FOXO and PGC-1α expression, superoxide dismutase (SOD) activity and NAD+ levels, and it prevented HFD-induced or cardiac Nmnat knockdown-induced cardiac lipid accumulation, malondialdehyde (MDA) content and fibrillation increase, and fractional shortening decrease.
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