Strain, stress, neurodegeneration and longevity

Gilad, Gad M.; Gilad, Varda H.

doi:10.1016/0047-6374(94)01529-u

Cited by 64 publications

(29 citation statements)

References 34 publications

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“…Associations of the quality of the response to stressful stimuli, longevity, and decreased neurodegeneration were reported in different mice strains (19). In the present study, a similar relationship was observed in terms of life span, biochemical markers of oxidative stress, and performance in behavioral tests on aging in the four experimental groups: slow males, fast males, slow females, and fast females.…”

Section: Discussionsupporting

confidence: 71%

“…The life span of rodent strains was found inversely related to the intensity of their behavioral and neuroendocrine responses to stress, this type of evidence suggesting a genetic linkage between the quality of response to stress, the performance in behavioral tests, the rate of age-dependent neurodegeneration, and life span (12,13,19).…”

mentioning

confidence: 97%

“…neuromuscular impairment; NADH-cytochrome c reductase BOTH AGING AND AGE-ASSOCIATED neurodegeneration are related to the development of behavioral impairments; consequently, decreased performances in neuromuscular coordination and exploratory tests are considered markers of neurological aging (15). The life span of rodent strains was found inversely related to the intensity of their behavioral and neuroendocrine responses to stress, this type of evidence suggesting a genetic linkage between the quality of response to stress, the performance in behavioral tests, the rate of age-dependent neurodegeneration, and life span (12,13,19).The likely molecular candidates responsible for the neuromuscular deficits are oxidizing free radicals and the consequent oxidative stress they generate. The free radical theory of aging, understood as the decline of biological function on time, is complemented with the concept that life span is a consequence of oxygen toxicity at 20 kPa O 2 (18, 21).…”

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confidence: 99%

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Behavioral dysfunction, brain oxidative stress, and impaired mitochondrial electron transfer in aging mice

Navarro¹,

Pino²,

Gómez³

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

201

147

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Behavioral dysfunction, brain oxidative stress, and impaired mitochondrial electron transfer in aging mice. Am J Physiol Regulatory Integrative Comp Physiol 282: R985-R992, 2002; 10.1152/ajpregu.00537.2001.-Behavioral tests, tightrope success, and exploratory activity in a T maze were conducted with male and female mice for 65 wk. Four groups were defined: the lower performance slow males and slow females and the higher performance fast males and fast females. Fast females showed the longest life span and the highest performance, and slow males showed the lowest performance and the shortest life span. Oxidative stress and mitochondrial electron transfer activities were determined in brain of young (28 wk), adult (52 wk), and old (72 wk) mice in a crosssectional study. Brain thiobarbituric acid reactive substances (TBARS) were increased by 50% in old mice and were ϳ15% higher in males than in females and in slow than in fast mice. Brain Cu,Zn-superoxide dismutase (SOD) activity was increased by 52% and Mn-SOD by 108% in old mice. The activities of mitochondrial enzymes NADH-cytochrome c reductase, cytochrome oxidase, and citrate synthase were decreased by 14-58% in old animals. The cumulative toxic effects of oxyradicals are considered the molecular mechanism of the behavioral deficits observed on aging. neuromuscular impairment; NADH-cytochrome c reductase BOTH AGING AND AGE-ASSOCIATED neurodegeneration are related to the development of behavioral impairments; consequently, decreased performances in neuromuscular coordination and exploratory tests are considered markers of neurological aging (15). The life span of rodent strains was found inversely related to the intensity of their behavioral and neuroendocrine responses to stress, this type of evidence suggesting a genetic linkage between the quality of response to stress, the performance in behavioral tests, the rate of age-dependent neurodegeneration, and life span (12,13,19).The likely molecular candidates responsible for the neuromuscular deficits are oxidizing free radicals and the consequent oxidative stress they generate. The free radical theory of aging, understood as the decline of biological function on time, is complemented with the concept that life span is a consequence of oxygen toxicity at 20 kPa O 2 (18, 21). When the free radical theory of aging (21) is focused in mitochondria, it becomes more attractive as the mitochondrial hypothesis of aging (22,30,37 • that act as intermediates and, among others, the stable products of the oxidation of unsaturated fatty acids, proteins, and DNA. Thiobarbituric acid reactive substances (TBARS), protein carbonyls, and 8-hydroxy-deoxyguanosine (8-OH-dG) are the usual markers of oxidative stress as byproducts of free radical-mediated oxidation of cell components. The first aim of this study, in accordance with the mitochondrial hypothesis of aging, was to assess oxidative stress and mitochondrial electron transfer in aging animals. The second aim was to establish the relationships between oxidative stress mar...

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Section: Discussionsupporting

confidence: 71%

mentioning

confidence: 97%

mentioning

confidence: 99%

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Behavioral dysfunction, brain oxidative stress, and impaired mitochondrial electron transfer in aging mice

Navarro¹,

Pino²,

Gómez³

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

201

147

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“…For example, in rats, freezing or slower maze performance predicts a premature aging syndrome, cognitive decline, lower antioxidants, and higher oxidative stress. 142,143 Further, greater behavioral reactivity or arousal is linked to shorter lifespan. 143 From an evolutionary perspective, anxiety prone individuals, those who tend to vigilantly monitor the environment, should do well in times of acute stress, but when exposed to chronic stress, the common condition in modern society, she or he will suffer from greater levels of allostatic load than other types of responders, such as those responding with anger rather than fear and anxiety.…”

Section: Biochemical Stressors Are Linked To Other Cell Aging Mechanismsmentioning

confidence: 99%

“…142,143 Further, greater behavioral reactivity or arousal is linked to shorter lifespan. 143 From an evolutionary perspective, anxiety prone individuals, those who tend to vigilantly monitor the environment, should do well in times of acute stress, but when exposed to chronic stress, the common condition in modern society, she or he will suffer from greater levels of allostatic load than other types of responders, such as those responding with anger rather than fear and anxiety. 144 While there is no 'one to one' mapping of personality onto stress response, in general, the exaggerated cortisol response appears to be most typical of people with a cognitive style characteristic of greater trait anxiety.…”

Section: Biochemical Stressors Are Linked To Other Cell Aging Mechanismsmentioning

confidence: 99%

Psychological and metabolic stress: A recipe for accelerated cellular aging?

Epel

2009

368

325

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Chronic stress can affect human health through a myriad of behavioral and biochemical pathways. Τhis review focuses on some key hormonal and metabolic pathways that appear important today. In modern society, we are faced with excessive psychological stress, as well as an epidemic of overeating, and the two together appear to have synergistic effects. Chronic stress can lead to overeating, co-elevation of cortisol and insulin, and suppression of certain anabolic hormones. This state of metabolic stress in turn promotes abdominal adiposity. Both the direct stress response and the accumulation of visceral fat can promote a milieu of systemic inflammation and oxidative stress. This biochemical environment appears to be conducive to several cell aging mechanisms, mainly dampening telomerase and leading to telomere length (TL) shortening and cell senescence. Immune cell telomere shortness is linked with many chronic disease states and earlier mortality. In this way, chronic stress may influence a variety of diseases through a biochemical cascade leading to immune cell senescence. Certain psychological temperaments at high risk of this stress cascade (mainly anxiety prone), gene-environment interactions, and potential interventions for interrupting the stress-aging cascade are discussed.

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A unifying hypothesis of Alzheimer's disease. III. Risk factors

Heininger

2000

Hum. Psychopharmacol. Clin. Exp.

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Normal ageing and Alzheimer's disease (AD) have many features in common and, in many respects, both conditions only differ by quantitative criteria. A variety of genetic, medical and environmental factors modulate the ageing-related processes leading the brain into the devastation of AD. In accordance with the concept that AD is a metabolic disease, these risk factors deteriorate the homeostasis of the Ca(2+)-energy-redox triangle and disrupt the cerebral reserve capacity under metabolic stress. The major genetic risk factors (APP and presenilin mutations, Down's syndrome, apolipoprotein E4) are associated with a compromise of the homeostatic triangle. The pathophysiological processes leading to this vulnerability remain elusive at present, while mitochondrial mutations can be plausibly integrated into the metabolic scenario. The metabolic leitmotif is particularly evident with medical risk factors which are associated with an impaired cerebral perfusion, such as cerebrovascular diseases including stroke, cardiovascular diseases, hypo- and hypertension. Traumatic brain injury represents another example due to the persistent metabolic stress following the acute event. Thyroid diseases have detrimental sequela for cerebral metabolism as well. Furthermore, major depression and presumably chronic stress endanger susceptible brain areas mediated by a host of hormonal imbalances, particularly the HPA-axis dysregulation. Sociocultural and lifestyle factors like education, physical activity, diet and smoking may also modulate the individual risk affecting both reserve capacity and vulnerability. The pathophysiological relevance of trace metals, including aluminum and iron, is highly controversial; at any rate, they may adversely affect cellular defences, antioxidant competence in particular. The relative contribution of these factors, however, is as individual as the pattern of the factors. In familial AD, the genetic factors clearly drive the sequence of events. A strong interaction of fat metabolism and apoE polymorphism is suggested by intercultural epidemiological findings. In cultures, less plagued by the 'blessings' of the 'cafeteria diet-sedentary' Western lifestyle, apoE4 appears to be not a risk factor for AD. This intriguing evidence suggests that, analogous to cardiovascular diseases, apoE4 requires a hyperlipidaemic lifestyle to manifest as AD risk factor. Overall, the etiology of AD is a key paradigm for a gene-environment interaction. Copyright 2000 John Wiley & Sons, Ltd.

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Strain, stress, neurodegeneration and longevity

Cited by 64 publications

References 34 publications

Behavioral dysfunction, brain oxidative stress, and impaired mitochondrial electron transfer in aging mice

Behavioral dysfunction, brain oxidative stress, and impaired mitochondrial electron transfer in aging mice

Psychological and metabolic stress: A recipe for accelerated cellular aging?

A unifying hypothesis of Alzheimer's disease. III. Risk factors

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