自然老化動物を用いた酸化ストレスの解析と抗老化研究

Abstract

Since Harman proposed the``free-radical theory of aging'', oxidative stress is postulated to be a major causal factor of senescence. Accumulation of oxidative stress-induced oxidatively modiˆed macromolecules including protein, DNA, and lipid, were found in tissues during the aging process. However, it is not necessarily clear which factor is more critical for an increase in endogenous reactive oxygen and/or decrease in antioxidative defense, to the age-related increase in oxidative damage. To clarify the production of reactive oxygen increasing with age, we examined reactive oxygen-dependent chemiluminescent (CL) signals in ex-vivo brain slices prepared from diŠerent aged animal brain during hypoxia-reoxygenation treatment using a novel photonic imaging method. CL signal was intensiˆed during reoxygenation. The signals in SAMP10 (short life strain) and SAMR1 (control) brain slices increased with aging. The slope of increase of CL intensity with age in P10 was steeper than those in R1. Age-dependent increase of CL intensity was also observed in C57BL/6 mouse, Wistar rat, and pigeon. However, SOD activity in brain was not changed with age. These results suggest that reactive oxygen production itself increase with aging. The rate of age-related increase of CL intensity was inversely related to the maximum life span of the animals. We speculate that reactive oxygen may be a kind of signal for aging and its levels in tissue may determine the aging process and life span. To decelerate the age-related increases of reactive oxygen production is expected as a potent strategy for anti-aging interventions.

Metal-Sulfate Induced Generation of ROS in Human Brain Cells: Detection Using an Isomeric Mixture of 5- and 6-Carboxy-2′,7′-Dichlorofluorescein Diacetate (Carboxy-DCFDA) as a Cell Permeant Tracer

“…Indeed, it is well documented that HNG cells in primary culture are exquisitely sensitive to externally applied stressors in the low nanomolar range, and that excessive ROS generation in brain cells and CNS tissues rapidly promotes cellular oxidative stress that progressively renders normally functioning DNA, lipids, proteins and RNA incapable of performing their homeostatic metabolic and cell-signaling functions. These ideas have been interpreted to support of the free-radical theory of aging [1,4,5,10,11,14–16,27–32]. Aging is the greatest known risk factor for the onset of neurodegenerative diseases such as sporadic Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and related, progressive, incurable neurological disorders including Parkinson’s disease (PD), prion disease and others [4–14,26].…”

Enhanced memory in Wistar rats by virgin coconut oil is associated with increased antioxidative, cholinergic activities and reduced oxidative stress

“…Oxidative stress is postulated to be a major causal factor of senescence. Accumulation of oxidative stress such as ROS in tissues during aging process modifies macromolecules including protein, DNA and lipid (Sasaki 2010 ). Antioxidants like SOD, CAT, GSH, GPx and GR are mutually supportive team of defence against oxidative assault by ROS and lipid peroxidation (Priya et al.…”

Protein and DNA Oxidation in Different Anatomic Regions of Rat Brain in a Mimetic Ageing Model

“…When the cellular redox balance shifts towards oxidants, it is called oxidative stress/damage [4]. Denham Harman’s theory suggests that free radicals may play a crucial role in the ageing process of cells [5,6]. Increased production of free radicals or insufficiency of antioxidant activity in defence leads to oxidative damage in cellular macromolecules [7].…”