Impaired autophagy activity is linked to elevated ER-stress and inflammation in aging adipose tissue

Ghosh, Amiya K.; Mau, Theresa; O’Brien, Martin; Garg, Sanjay; Yung, Raymond

doi:10.18632/aging.101083

Cited by 68 publications

(54 citation statements)

References 52 publications

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“…On the other hand, impaired autophagic degradation can trigger ER stress. Ghosh et al [22] demonstrated that impaired autophagy in mouse adipose tissue from old animals Fig. 1 ER stress evokes inflammatory responses via the activation of three branches of ER stress sensors.…”

Section: Er Stress Stimulates Upr Signalingmentioning

confidence: 99%

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

2020

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The endoplasmic reticulum (ER) contains stress sensors which recognize the accumulation of unfolded proteins within the lumen of ER, and subsequently these transducers stimulate the unfolded protein response (UPR). The ER sensors include the IRE1, PERK, and ATF6 transducers which activate the UPR in an attempt to restore the quality of protein folding and thus maintain cellular homeostasis. If there is excessive stress, UPR signaling generates alarmins, e.g., chemokines and cytokines, which activate not only tissue-resident immune cells but also recruit myeloid and lymphoid cells into the affected tissues. ER stress is a crucial inducer of inflammation in many pathological conditions. A chronic low-grade inflammation and cellular senescence have been associated with the aging process and many age-related diseases, such as Alzheimer's disease. Currently, it is known that immune cells can exhibit great plasticity, i.e., they are able to display both pro-inflammatory and anti-inflammatory phenotypes in a context-dependent manner. The microenvironment encountered in chronic inflammatory conditions triggers a compensatory immunosuppression which defends tissues from excessive inflammation. Recent studies have revealed that chronic ER stress augments the suppressive phenotypes of immune cells, e.g., in tumors and other inflammatory disorders. The activation of immunosuppressive network, including myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg), has been involved in the aging process and Alzheimer's disease. We will examine in detail whether the ER stress-related changes found in aging tissues and Alzheimer's disease are associated with the activation of immunosuppressive network, as has been observed in tumors and many chronic inflammatory diseases.

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Section: Er Stress Stimulates Upr Signalingmentioning

confidence: 99%

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

2020

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“…Finally, a reduced autophagic rate has been demonstrated to contribute to inflammation and endoplasmic reticulum stress in adipose tissue of aged mice, which suggests a role for autophagy in the metabolic derangements in aging adipose tissue (126). In fact, compromised autophagy activity in preadipocytes from aged mice was correlated with the enhanced release of proinflammatory cytokines, IL-6 and monocyte chemotactic protein-1 (126).…”

Section: Autophagy In Adipose Tissuementioning

confidence: 99%

Molecular mechanisms underlying metabolic syndrome: the expanding role of the adipocyte

et al. 2017

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The metabolic syndrome (MetS) is defined as a cluster of 3 or more metabolic and cardiovascular risk factors and represents a serious problem for public health. Altered function of adipose tissue has a significant impact on whole-body metabolism and represents a key driver for the development of these metabolic derangements, collectively referred as to MetS. In particular, increased visceral and ectopic fat deposition play a major role in the development of insulin resistance and MetS. A large body of evidence demonstrates that aging and MetS share several metabolic alterations. Of importance, molecular pathways that regulate lifespan affect key processes of adipose tissue physiology, and transgenic mouse models with adipose-specific alterations in these pathways show derangements of adipose tissue and other metabolic features of MetS, which highlights a causal link between dysfunctional adipose tissue and deleterious effects on whole-body homeostasis. This review analyzes adipose tissue-specific dysfunctions, including metabolic alterations that are related to aging, that have a significant impact on the development of MetS.-Armani, A., Berry, A., Cirulli, F., Caprio, M. Molecular mechanisms underlying metabolic syndrome: the expanding role of the adipocyte.

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“…For example, a study examining autophagy and ER stress in aging adipose tissue-derived stromal vascular fraction cells (SVF) demonstrates that aged SVF cells exhibit decreased autophagy and increased ER-stress [74]. Furthermore, the loss of autophagy in mouse colorectal tumors via genetic inhibition of ATG5 or treatment with the lysosomal inhibitor chloroquine lead to elevated ER stress as well as increased CHOP and BiP expression [75].…”

Section: Er Stress and Mtor Signaling During Detachment-induced Autopmentioning

confidence: 99%

The Interconnections between Autophagy and Integrin-Mediated Cell Adhesion

Vlahakis

Debnath

2017

Journal of Molecular Biology

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Autophagy is a cellular degradation process integral for promoting cellular adaptation during metabolic stress while also functioning as a cellular homeostatic mechanism. Mounting evidence also demonstrates that autophagy is induced upon loss of integrin-mediated cell attachments to the surrounding extracellular matrix (ECM). Analogous to its established cytoprotective role during nutrient starvation, autophagy protects cells from detachment-induced cell death, termed anoikis. Here, we review the significance of autophagy as an anoikis resistance pathway, focusing on the intracellular signals associated with integrins that modulate the autophagy response and dictate the balance between cell death and survival following loss of cell-matrix contact. In addition, we highlight recent studies demonstrating that autophagy functions in the upstream regulation of integrin-mediated cell adhesion via the control of focal adhesion remodeling, and discuss how these emerging interconnections between integrin-mediated adhesion pathways and autophagy influence cancer progression and metastasis.

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Impaired autophagy activity is linked to elevated ER-stress and inflammation in aging adipose tissue

Cited by 68 publications

References 52 publications

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

Molecular mechanisms underlying metabolic syndrome: the expanding role of the adipocyte

The Interconnections between Autophagy and Integrin-Mediated Cell Adhesion

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