Lifespan extension and increased resistance to environmental stressors by N-acetyl-L-cysteine in Caenorhabditis elegans.

OBJECTIVE: This study was performed to determine the effect of N-acetyl-L-cysteine, a modified sulfur-containing amino acid that acts as a strong cellular antioxidant, on the response to environmental stressors and on aging in C. elegans. METHOD: The survival of worms under oxidative stress conditions induced by paraquat was evaluated with and without in vivo N-acetyl-L-cysteine treatment. The effect of N-acetyl-L-cysteine on the response to other environmental stressors, including heat stress and ultraviolet irradiation (UV), was also monitored. To investigate the effect on aging, we examined changes in lifespan, fertility, and expression of age-related biomarkers in C. elegans after N-acetyl-L-cysteine treatment. RESULTS: Dietary N-acetyl-L-cysteine supplementation significantly increased resistance to oxidative stress, heat stress, and UV irradiation in C. elegans. In addition, N-acetyl-L-cysteine supplementation significantly extended both the mean and maximum lifespan of C. elegans. The mean lifespan was extended by up to 30.5% with 5 mM N-acetyl-L-cysteine treatment, and the maximum lifespan was increased by 8 days. N-acetyl-L-cysteine supplementation also increased the total number of progeny produced and extended the gravid period of C. elegans. The green fluorescent protein reporter assay revealed that expression of the stress-responsive genes, sod-3 and hsp-16.2, increased significantly following N-acetyl-L-cysteine treatment. CONCLUSION: N-acetyl-L-cysteine supplementation confers a longevity phenotype in C. elegans, possibly through increased resistance to environmental stressors.

Analysis of cerebral blood flow of subcortical vascular dementia with single photon emission computed tomography: adaptation of statistical parametric mapping.

BACKGROUND AND OBJECTIVES: Subcortical vascular dementia (VaD) is a relatively homogeneous subtype of VaD, but the mechanisms of cognitive dysfunction of subcortical VaD are not fully understood. This study investigates the changes of cerebral blood flow (CBF) in patients with subcortical VaD and the contribution of the white matter hyperintensity (WMHI) and clinical severity to CBF changes. METHODS: 99mTc-ethyl cysteinate dimer single photon emission computed tomography (SPECT) was performed to measure the regional CBF and statistical parametric mapping SPM99 software was applied to automated and objective analysis of the SPECT image data. Twenty-three patients (12 male, 11 female) with mild to moderate dementia who met both the criteria of the DSM-IV and probable and possible NINDS-AIREN for VaD and had subcortical white matter changes and lacunar infarctions in brain MRI were evaluated against 17 normal control subjects (7 male, 10 female). The severity of the WMHI was measured by the semi-quantitative scale method proposed by Mäntyla. The Clinical Dementia Rating scale measured the severity of dementia. RESULTS: SPM analysis of the SPECT image reveals significantly reduced regional CBF in the right thalamus, left caudate nucleus, cingulate, bilateral superior temporal, and left ventral subcallosal gyri in subcortical VaD patients compared to the normal controls (corrected P<0.001). Of four WMHIs, only the deep WMHI was associated with the small CBF reduction in the left superior temporal gyrus (uncorrected P<0.01). The reduction of the CBF according to the severity of dementia was noted in the anterior and posterior association areas (uncorrected P<0.01). CONCLUSIONS: Our study suggests that cognitive dysfunction of subcortical VaD may be related to the reduction of the CBF in the brain areas mentioned, which are probably not associated with the severity of periventricular WMHI and dementia.

Acanthopanax sessiliflorus stem confers increased resistance to environmental stresses and lifespan extension in Caenorhabditis elegans.

BACKGROUND/OBJECTIVES: Acanthopanax sessiliflorus is a native Korean plant and used as traditional medicine or an ingredient in many Korean foods. The free radical theory of aging suggests that cellular oxidative stress caused by free radicals is the main cause of aging. Free radicals can be removed by cellular anti-oxidants. MATERIALS/METHODS: Here, we examined the anti-oxidant activity of Acanthopanax sessiliflorus extract both in vitro and in vivo. Survival of nematode C. elegans under stress conditions was also compared between control and Acanthopanax sessiliflorus extract-treated groups. Then, anti-aging effect of Acanthopanax sessiliflorus extract was monitored in C. elegans. RESULTS: Stem extract significantly reduced oxidative DNA damage in lymphocyte, which was not observed by leaves or root extract. Survival of C. elegans under oxidative-stress conditions was significantly enhanced by Acanthopanax sessiliflorus stem extract. In addition, Acanthopanax sessiliflorus stem increased resistance to other environmental stresses, including heat shock and ultraviolet irradiation. Treatment with Acanthopanax sessiliflorus stem extract significantly extended both mean and maximum lifespan in C. elegans. However, fertility was not affected by Acanthopanax sessiliflorus stem. CONCLUSION: Different parts of Acanthopanax sessiliflorus have different bioactivities and stem extract have strong anti-oxidant activity in both rat lymphocytes and C. elegans, and conferred a longevity phenotype without reduced reproduction in C. elegans, which provides conclusive evidence to support the free radical theory of aging.

Treadmill exercise ameliorates symptoms of methimazole-induced hypothyroidism through enhancing neurogenesis and suppressing apoptosis in the hippocampus of rat pups.

Thyroid hormones play a crucial role in new neuron production and maturation during brain development. Physical exercise is known to promote cell survival and functional recovery after brain injuries. In the present study, we investigated the effects of treadmill exercise on short-term memory, spatial learning ability, neurogenesis, and apoptosis in hypothyroidism rat pups. On the 14th perinatal day, the pregnant rats were divided into two groups: the maternal control group and the maternal methimazole (MMI)-treated group. For the induction of hypothyroidism in rat pups, MMI was added to the drinking water (0.02%, wt/vol), from the 14th prenatal day to the 49th postnatal day. After delivery, the male rat pups born from the maternal control group were assigned into the control group and the control and exercise group. The rat pups born from the maternal MMI-treated group were divided into the hypothyroidism-induction group and the hypothyroidism-induction and treadmill exercise group. The rat pups in the exercise groups were forced to run on a motorized treadmill for 30min once a day, starting on the 22nd postnatal day for 4 weeks. Induction of hypothyroidism during the fetal and early postnatal period showed suppression of neurogenesis and enhancement of apoptosis in the hippocampus. Short-term memory and spatial learning ability were deteriorated in the hypothyroidism rat pups. Treadmill exercise during the postnatal period increased neurogenesis and inhibited apoptosis, and resulted in the improvement of short-term memory and spatial learning ability in the hypothyroidism rat pups.

Lifespan extension and increased resistance to environmental stressors by N-Acetyl-L-Cysteine in Caenorhabditis elegans

OBJECTIVE: This study was performed to determine the effect of N-acetyl-L-cysteine, a modified sulfur-containing amino acid that acts as a strong cellular antioxidant, on the response to environmental stressors and on aging in C. elegans. METHOD: The survival of worms under oxidative stress conditions induced by paraquat was evaluated with and without in vivo N-acetyl-L-cysteine treatment. The effect of N-acetyl-L-cysteine on the response to other environmental stressors, including heat stress and ultraviolet irradiation (UV), was also monitored. To investigate the effect on aging, we examined changes in lifespan, fertility, and expression of age-related biomarkers in C. elegans after N-acetyl-L-cysteine treatment. RESULTS: Dietary N-acetyl-L-cysteine supplementation significantly increased resistance to oxidative stress, heat stress, and UV irradiation in C. elegans. In addition, N-acetyl-L-cysteine supplementation significantly extended both the mean and maximum lifespan of C. elegans. The mean lifespan was extended by up to 30.5% with 5 mM N-acetyl-L-cysteine treatment, and the maximum lifespan was increased by 8 days. N-acetyl-L-cysteine supplementation also increased the total number of progeny produced and extended the gravid period of C. elegans. The green fluorescent protein reporter assay revealed that expression of the stress-responsive genes, sod-3 and hsp-16.2, increased significantly following N-acetyl-L-cysteine treatment. CONCLUSION: N-acetyl-L-cysteine supplementation confers a longevity phenotype in C. elegans, possibly through increased resistance to environmental stressors. .