The fat cell senescence hypothesis

Newsholme, Philip; Bittencourt, Paulo Ivo Homem de

doi:10.1097/mco.0000000000000077

Cited by 79 publications

(53 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently, any tiny impairment in the ability of cells to respond to stress via iHSP70 expression (i.e., the HS response) may have profound consequences to cell viability, tissue repair and, as a corollary, to organism longevity. Unfortunately, however, aging and age-related chronic inflammatory diseases are marked up by a conspicuous depression of stress-elicited HS response [7]. Additionally, iHSP70 expression is decreased during muscle inactivity and aging, and evidence supports the loss of iHSP70 as a key mechanism which may drive muscle atrophy, contractile dysfunction, and reduced regenerative capacity associated with these conditions.…”

Section: Anti-misfolding Protein Quality Control Systemsmentioning

confidence: 99%

“…This is noteworthy because people with RA die at a younger age than people without the disease, whereas age exerts an exponentially increasing effect on CVD risk in RA patients [21]. RA is characterized by a sequence of age-dependent degenerative conditions that usually starts with an acute inflammatory reaction, followed by a continuous pro-inflammatory overburden that induces endocrinosenescence, neurosenescence, and senescence of the muscular system [7,22]. Age-related premature atherosclerosis has also been recognized as an important factor in the morbidity and mortality of patients with systemic lupus erythematosus (SLE), this being attributed to vasculitis and corticosteroid use by these patients [22].…”

Section: Age-related Inflammatory Diseases Of High Prevalencementioning

confidence: 99%

“…Such inflammatory diseases have underlying basis on chronic overburden of protein quality control, which leads to the formation of protein aggregates that triggers more inflammatory signals; this eternalizes inflammation that spreads throughout the body [7]. Hence, understanding of intracellular protein quality control system (the chaperone machinery and the HS response) is crucial for adequately treating age-related chronic degenerative diseases.…”

Section: Age-related Inflammatory Diseases Of High Prevalencementioning

confidence: 99%

“…HSP70 is a cytoprotective and anti-inflammatory molecular chaperone primarily devoted to avoid protein misfolding and to correct unfolded proteins, thus allowing for the proteins homeostasis (i.e., proteostasis) within the cellular compartments [7,34]. Since proteostasis-threatening situations rapidly evoke a strong expression of HSP70, intracellularly located HSP70 (iHSP70) is, as a consequence, a universal marker of stress.…”

Section: Anti-misfolding Protein Quality Control Systemsmentioning

confidence: 99%

“…Specifically, adipose tissue expansion is linked to a state of chronic unresolved inflammation [7] that, when associated with aging, is often called "inflammaging". This term has been coined to highlight the increased levels of circulating pro-inflammatory molecules that is observed in older people [8] and is a common feature not only in aging but also in obesity and diabetes [9,10].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

Leite

Cruzat

Krause

et al. 2016

Nutrire

View full text Add to dashboard Cite

Aging is an intricate process modulated by different molecular and cellular events, such as genome instability, epigenetic and transcriptional changes, molecular damage, cell death and senescence, inflammation, and metabolic dysfunction. Particularly, protein quality control (chaperone systems) tends to be negatively affected by aging, thus leading to cellular senescence in metabolic tissues and, as a consequence, to the increasing dissemination of inflammation throughout the body. The heat shock (HS) response and its associated expression of the 70 kDa family of heat shock proteins (HSP70), which are anti-inflammatory molecular chaperones, are found to be markedly decreased during muscle inactivity and aging, while evidence supports the loss of HSP70 as a key mechanism which may drive muscle atrophy, contractile dysfunction, and reduced regenerative capacity. In addition, abnormal stress response is linked with higher incidence of neurodegenerative diseases as well as low-grade inflammatory diseases that are associated with physical inactivity and obesity. Therefore, strategies to increase or, at least, to maintain the levels of HSP70, and its accompanying HS response to stress, are key to reduce biological cell dysfunctions that occur in aging. In this sense, physical exercise is of note as it is the most powerful inducer of the HS response, comparable only to heat stress and fever-like conditions. On the other hand, the amino acid L-glutamine, whose production within the skeletal muscle and liberation into the blood stream is dependent on muscle activity, is a potentializer of HSP70 expression and HS response, particularly via its entering in hexosamine biosynthetic pathway (HBP). Herein, we discuss the collaborative role of glutamine (and its donors/precursors) and physical exercise (mostly responsible for glutamine release into the circulation) as potential tools to increase HSP70 expression and the HS response in the elderly.

show abstract

Section: Anti-misfolding Protein Quality Control Systemsmentioning

confidence: 99%

Section: Age-related Inflammatory Diseases Of High Prevalencementioning

confidence: 99%

Section: Age-related Inflammatory Diseases Of High Prevalencementioning

confidence: 99%

Section: Anti-misfolding Protein Quality Control Systemsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

Leite

Cruzat

Krause

et al. 2016

Nutrire

View full text Add to dashboard Cite

show abstract

The sirtuins: Markers of metabolic health

Covington

Bajpeyi

2015

Molecular Nutrition Food Res

View full text Add to dashboard Cite

The sirtuins represent a class of proteins first discovered orthologus to the yeast silent information regulator 2 protein that have been retained in mammalian species. Currently, seven sirtuins have been identified in humans, and their functions currently surpass their originally identified role as histone deacetylase and chromatin silencers to encompass nutrient sensing and metabolic function. All seven sirtuins require NAD(+) in order to carry out their enzymatic activity, and thus become activated in conditions of nutrient depletion, starvation, and cellular stress. Caloric restriction and increased physical activity have been postulated, though perhaps controversially, to mediate sirtuin function. Here, we review the current literature surrounding the functions of the seven human sirtuins, mediators of their function, and the roles they play in metabolic health related to dietary and physical activity interventions. Despite the controversy surrounding sirtuin function with regard to longevity, we have aimed to show that regardless of its effects on aging, sirtuin function is pivotal to pathways involving metabolic health, and should therefore be investigated with regard to improving metabolic diseases such as obesity and type 2 diabetes.

show abstract

Obesity depresses the anti‐inflammatory HSP70 pathway, contributing to NAFLD progression

Naso

Porto

Fillmann

et al. 2014

Obesity

View full text Add to dashboard Cite

Objectives: To evaluate whether reduced activity of the anti-inflammatory HSP70 pathway correlates with nonalcoholic fatty liver disease (NAFLD) progression and with markers of oxidative stress because obesity activates inflammatory JNKs, whereas HSP70 exerts the opposite effect. Methods: Adult obese patients (N 5 95) undergoing bariatric surgery were divided into steatosis (ST), steatohepatitis (SH), and fibrosis (SH1F) groups. The levels of HSP70, its major transcription factor, HSF1, and JNKs were assessed by immunoblotting hepatic and visceral adipose tissue; data were confirmed by immunohistochemistry. Plasma biochemistry (lipids, HbA 1c , HOMA, hepatic enzymes, and redox markers) was also evaluated. Results: In both liver and adipose tissue, decreased HSP70 levels, paralleled by similar reductions in HSF1 and reduced plasma antioxidant enzyme activities, correlated with insulin resistance and with NAFLD progression (expression levels were as follows: ST > SH > SH 1 F). The immunohistochemistry results suggested Kupffer cells as a site of HSP70 inhibition. Conversely, JNK1 content and phosphorylation increased. Conclusions: Decreased HSF1 levels in the liver and fat of obese patients correlated with impairment of HSP70 in an NAFLD stage-dependent manner. This impairment may affect HSP70-dependent anti-inflammation, with consequent oxidative stress and insulin resistance in advanced stages of NAFLD. Possible causal effects of fat cell senescence are discussed.

show abstract

The fat cell senescence hypothesis

Cited by 79 publications

References 73 publications

Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

The sirtuins: Markers of metabolic health

Obesity depresses the anti‐inflammatory HSP70 pathway, contributing to NAFLD progression

Contact Info

Product

Resources

About