The brain and immune system prompt energy shortage in chronic inflammation and ageing

Straub, Rainer H.

doi:10.1038/nrrheum.2017.172

Cited by 120 publications

(83 citation statements)

References 86 publications

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“…Metabolic diseases are often associated with over-activated inflammatory response, for example obesity and diabetes ( Straub, 2017 ). Delaminating pathogenic factors of the disease progression lead to reduced inflammation.…”

Section: Pharmacological Activities Of Celastrolmentioning

confidence: 99%

A Mechanistic Overview of Triptolide and Celastrol, Natural Products from Tripterygium wilfordii Hook F

et al. 2018

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Triptolide and celastrol are predominantly active natural products isolated from the medicinal plant Tripterygium wilfordii Hook F. These compounds exhibit similar pharmacological activities, including anti-cancer, anti-inflammation, anti-obesity, and anti-diabetic activities. Triptolide and celastrol also provide neuroprotection and prevent cardiovascular and metabolic diseases. However, toxicity restricts the further development of triptolide and celastrol. In this review, we comprehensively review therapeutic targets and mechanisms of action, and translational study of triptolide and celastrol. We systemically discuss the structure-activity-relationship of triptolide, celastrol, and their derivatives. Furthermore, we propose the use of structural derivatives, targeted therapy, and combination treatment as possible solutions to reduce toxicity and increase therapeutic window of these potent natural products from T. wilfordii Hook F.

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Section: Pharmacological Activities Of Celastrolmentioning

confidence: 99%

A Mechanistic Overview of Triptolide and Celastrol, Natural Products from Tripterygium wilfordii Hook F

et al. 2018

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“…Chronic low-grade inflammation has been estimated to increase systemic energy expenditure by up to 10% (Straub, 2017 ). Given the increased energy demand of chronic inflammation, and the resulting reduced energy availability, one would expect that behavioral -energy expenditure (i.e., amount of energy spent on activities) would decrease.…”

Section: Effects Of Low-grade Inflammation On Energy Production and Ementioning

confidence: 99%

The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure

Lacourt

Vichaya

Chiu

et al. 2018

Front. Behav. Neurosci.

133

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Chronic or persistent fatigue is a common, debilitating symptom of several diseases. Persistent fatigue has been associated with low-grade inflammation in several models of fatigue, including cancer-related fatigue and chronic fatigue syndrome. However, it is unclear how low-grade inflammation leads to the experience of fatigue. We here propose a model of an imbalance in energy availability and energy expenditure as a consequence of low-grade inflammation. In this narrative review, we discuss how chronic low-grade inflammation can lead to reduced cellular-energy availability. Low-grade inflammation induces a metabolic switch from energy-efficient oxidative phosphorylation to fast-acting, but less efficient, aerobic glycolytic energy production; increases reactive oxygen species; and reduces insulin sensitivity. These effects result in reduced glucose availability and, thereby, reduced cellular energy. In addition, emerging evidence suggests that chronic low-grade inflammation is associated with increased willingness to exert effort under specific circumstances. Circadian-rhythm changes and sleep disturbances might mediate the effects of inflammation on cellular-energy availability and non-adaptive energy expenditure. In the second part of the review, we present evidence for these metabolic pathways in models of persistent fatigue, focusing on chronic fatigue syndrome and cancer-related fatigue. Most evidence for reduced cellular-energy availability in relation to fatigue comes from studies on chronic fatigue syndrome. While the mechanistic evidence from the cancer-related fatigue literature is still limited, the sparse results point to reduced cellular-energy availability as well. There is also mounting evidence that behavioral-energy expenditure exceeds the reduced cellular-energy availability in patients with persistent fatigue. This suggests that an inability to adjust energy expenditure to available resources might be one mechanism underlying persistent fatigue.

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“…The prevalence of chronic pain is increased in older adults (adjusted odds ratios [ORs] of 3.4‐4.0) due to increased chronic disease and age‐related alterations in homeostatic function and regulation of peripheral immune and neuroimmune cells . Insomnia is associated with increased chronic pain, partially mediated by depressive and anxiety symptoms .…”

mentioning

confidence: 99%

“…7,8 The prevalence of chronic pain is increased in older adults (adjusted odds ratios [ORs] of 3.4-4.0) due to increased chronic disease and age-related alterations in homeostatic function and regulation of peripheral immune and neuroimmune cells. 9,10 Insomnia is associated with increased chronic pain, partially mediated by depressive and anxiety symptoms. 11,12 Mechanistically, opioids and metabolites promote cellular inflammation through opioid 13 and toll-like receptor 4 14 receptor agonism resulting in tissue pathology, reduced recovery, and impaired function.…”

mentioning

confidence: 99%

Self‐Reported Prescription Drug Use for Pain and for Sleep and Incident Frailty

Cil

Park

Bergen

2019

J American Geriatrics Society

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OBJECTIVES We aimed to estimate incident frailty risks of prescription drugs for pain and for sleep in older US adults. DESIGN Longitudinal cohort. SETTING Health and Retirement Study. PARTICIPANTS Community‐living respondents aged 65 years and older, excluding individuals who received recent treatment for cancer (N = 14 208). Our longitudinal analysis sample included respondents who were not frail at baseline and had at least one follow‐up wave with complete information on both prescription drug use and frailty, or date of death (N = 7201). MEASUREMENTS Prescription drug use for pain and sleep, sociodemographics, other drug and substance use, and Burden frailty model components. Multivariable drug use stratified hazard models with death as a competing risk evaluated frailty risks associated with co‐use and single use of prescription drugs for pain and for sleep. RESULTS Proportions endorsing prescription drug use were 22.1% for pain only, 6.8% for sleep only, and 7.7% for both indications. Burden frailty model prevalence was 41.0% and varied significantly by drug use. Among non‐frail individuals at baseline, proportions endorsing prescription drug use were 14.9%, 5.6%, and 2.2% for the three indications. Prescription drug use was associated with increased risk of frailty (co‐use adjusted subhazard ratio [sHR] = 1.95; 95% confidence interval [CI] = 1.6‐2.4; pain only adjusted sHR = 1.58; CI = 1.4‐1.8; sleep‐only adjusted sHR = 1.35; CI = 1.1‐1.6; no use = reference group). Cumulative incidence of frailty over 8 years for the four groups was 60.6%, 50.9%, 45.8%, and 34.1%. Sensitivity analyses controlling for chronic diseases associated with persistent pain resulted in minor risk reductions. CONCLUSION Prescription pain and sleep drug use is significantly associated with increased incidence of frailty. Research to estimate effects of pain and sleep indications and of drug class–specific dosage and duration on incident frailty is indicated before advocating deprescribing based on these findings. J Am Geriatr Soc 67:2474–2481, 2019

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The brain and immune system prompt energy shortage in chronic inflammation and ageing

Cited by 120 publications

References 86 publications

A Mechanistic Overview of Triptolide and Celastrol, Natural Products from Tripterygium wilfordii Hook F

A Mechanistic Overview of Triptolide and Celastrol, Natural Products from Tripterygium wilfordii Hook F

The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure

Self‐Reported Prescription Drug Use for Pain and for Sleep and Incident Frailty

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