Neurodegeneration During Aging: The Role of Oxidative Stress Through Epigenetic Modifications

Srivas, Sweta; Baghel, Meghraj Singh; Singh, Padmanabh; Thakur, M. K.

doi:10.1007/978-981-13-3585-3_3

Cited by 4 publications

(3 citation statements)

References 74 publications

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“…A recent review concluded that epigenetic clocks provide a better indicator of biological aging than other markers, including proteomic predictors, transcriptomic predictors, telomere length, metabolomic predictors, and biomarkers [ 8 ]. Poor metabolic health, including oxidative stress [ 9 ] and chronic inflammation [ 10 ], is an important risk factor for epigenetic age acceleration [ 11 ]. Importantly, epigenetic aging is associated with future incidence of cardiovascular disease [ 12 ], cancer [ 13 ], diabetes [ 14 ], and all-cause mortality [ 15 ], independent of chronological aging.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Aging in Early Life: Role of Maternal and Early Childhood Nutrition

Koemel

Skilton

2022

Curr Nutr Rep

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Purpose of Review Early life presents a pivotal period during which nutritional exposures are more likely to cause epigenetic modifications, which may impact an individual’s health during adulthood. This article reviews the current evidence regarding maternal and early childhood nutritional exposures and their role in epigenetic aging. Recent Findings Maternal and early life consumption of diets higher in fiber, antioxidants, polyphenols, B vitamins, vitamin D, and ω-3 fatty acids is associated with slower epigenetic aging. Conversely, diets higher in glycemic load, fat, saturated fat, and ω-6 fatty acids demonstrate a positive association with epigenetic aging. Summary Maternal and early life nutrition directly and indirectly influences epigenetic aging via changes in one-carbon metabolism, cardiometabolic health, and the microbiome. Clinical trials are warranted to determine the specific foods, dietary patterns, and dietary supplements that will normalize or lower epigenetic aging across the life course.

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Section: Introductionmentioning

confidence: 99%

Epigenetic Aging in Early Life: Role of Maternal and Early Childhood Nutrition

Koemel

Skilton

2022

Curr Nutr Rep

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“…Previous studies have shown that oxidative stress regulates the epigenetic modifications [11,12]. Strivas et al demonstrated that oxidative stress-mediated epigenetic changes play a critical role in memory processes during aging in several neurological disorders and their recovery through antioxidant treatment [13]. Indeed, many studies have documented oxidative damage in both postmortem human ALS tissues and transgenic animal models [3,[14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Modulation of histone H3K4 dimethylation by spermidine ameliorates motor neuron survival and neuropathology in a mouse model of ALS

et al. 2022

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Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive paralysis due to motor neuron degeneration. It has been proposed that epigenetic modification and transcriptional dysregulation may contribute to motor neuron death. In this study, we investigate the basis for therapeutic approaches to target lysine-specific histone demethylase 1 (LSD1) and elucidate the mechanistic role of LSD1-histone H3K4 signaling pathway in ALS pathogenesis. Methods In order to examine the role of spermidine (SD), we administered SD to an animal model of ALS (G93A) and performed neuropathological analysis, body weight, and survival evaluation. Results Herein, we found that LSD1 activity is increased while levels of H3K4me2, a substrate of LSD1, is decreased in cellular and animal models of ALS. SD administration modulated the LSD1 activity and restored H3K4me2 levels in ChAT-positive motor neurons in the lumbar spinal cord of ALS mice. SD prevented cellular damage by improving the number and size of motor neurons in ALS mice. SD administration also reduced GFAP-positive astrogliogenesis in the white and gray matter of the lumbar spinal cord, improving the neuropathology of ALS mice. Moreover, SD administration improved the rotarod performance and gait analysis of ALS mice. Finally, SD administration delayed disease onset and prolonged the lifespan of ALS (G93A) transgenic mice. Conclusion Together, modulating epigenetic targets such as LSD1 by small compounds may be a useful therapeutic strategy for treating ALS.

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“…The oxidative phosphorylation-driven ROS generation is eliminated or neutralized by the antioxidant enzymes present in the brain. However, antioxidant defense systems are compromised in the aging brain, thus making it more vulnerable to ROS ( Mattson et al, 2008 ; Srivas et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress-mediated memory impairment during aging and its therapeutic intervention by natural bioactive compounds

Singh

Barman

Thakur

2022

Front. Aging Neurosci.

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Aging and associated neurodegenerative diseases are accompanied by the decline of several brain functions including cognitive abilities. Progressive deleterious changes at biochemical and physiological levels lead to the generation of oxidative stress, accumulation of protein aggregates, mitochondrial dysfunctions, loss of synaptic connections, and ultimately neurodegeneration and cognitive decline during aging. Oxidative stress that arises due to an imbalance between the rates of production and elimination of free radicles is the key factor for age-associated neurodegeneration and cognitive decline. Due to high energy demand, the brain is more susceptible to free radicals-mediated damages as they oxidize lipids, proteins, and nucleic acids, thereby causing an imbalance in the homeostasis of the aging brain. Animal, as well as human subject studies, showed that with almost no or few side effects, dietary interventions and plant-derived bioactive compounds could be beneficial to recovering the memory or delaying the onset of memory impairment. As the plant-derived bioactive compounds have antioxidative properties, several of them were used to recover the oxidative stress-mediated changes in the aging brain. In the present article, we review different aspects of oxidative stress-mediated cognitive change during aging and its therapeutic intervention by natural bioactive compounds.

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Neurodegeneration During Aging: The Role of Oxidative Stress Through Epigenetic Modifications

Cited by 4 publications

References 74 publications

Epigenetic Aging in Early Life: Role of Maternal and Early Childhood Nutrition

Epigenetic Aging in Early Life: Role of Maternal and Early Childhood Nutrition

Modulation of histone H3K4 dimethylation by spermidine ameliorates motor neuron survival and neuropathology in a mouse model of ALS

Oxidative stress-mediated memory impairment during aging and its therapeutic intervention by natural bioactive compounds

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