Hypoxia metabolism in ageing

Valli, Alessandro; Harris, Adrian L.; Kessler, Benedikt M.

doi:10.18632/aging.100782

Cited by 22 publications

(15 citation statements)

References 7 publications

(21 reference statements)

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“…It is reported that 2-hydroxyglutarate (2-HG), an oncometabolite produced by mutated isocitrate dehydrogenase (IDH) 1 and 2, catalytically inactivates the TET2 enzyme, and the mutation is also found in AML (∼20%), gliomas (60-80%), and cholangiocarcinomas (7-28%) (88). With advancing aging, a general decrease in O2 supply and impaired O2 diffusion to target tissues, caused by age-associated poor vascularization, leads to tissue hypoxia (89). Interestingly, a hypoxic environment helps mammalian cells increase the production of oncometabolite, 2-HG (88,90).…”

Section: Age-associated Mutations Impede Msc Niche Functionmentioning

confidence: 99%

Impact of Mesenchymal Stem Cell Senescence on Inflammaging

Lee

2020

BMB Rep.

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Life expectancy has dramatically increased around the world over the last few decades, and staying healthier longer, without chronic disease, has become an important issue. Although understanding aging is a grand challenge, our understanding of the mechanisms underlying the degeneration of cell and tissue functions with age and its contribution to chronic disease has greatly advanced during the past decade. As our immune system alters with aging, abnormal activation of immune cells leads to imbalance of innate and adaptiveimmunity and develops a persistent and mild systemic inflammation, inflammaging. With their unique therapeutic properties, such as immunomodulation and tissue regeneration, mesenchymal stem cells (MSCs) have been considered to be a promising source for treating autoimmune disease or as anti-aging therapy. Although direct evidence of the role of MSCs in inflammaging has not been thoroughly studied, features reported in senescent MSCs or the aging process of MSCs are associated with inflammaging; MSC niche-driven skewing of hematopoiesis toward the myeloid lineage or oncogenesis, production of pro-inflammatory cytokines, and weakening their modulative property on macrophage polarization, which plays a central role on inflammaging development. This review explores the role of senescent MSCs as an important regulator for onset and progression of inflammaging and as an effective target for anti-aging strategies. [BMB Reports 2020; 53(2): 65-73] BMB Rep. 2020; 53(2): 65-73

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Section: Age-associated Mutations Impede Msc Niche Functionmentioning

confidence: 99%

Impact of Mesenchymal Stem Cell Senescence on Inflammaging

Lee

2020

BMB Rep.

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“…For example, it has been shown in aged murine adipose tissue stromal cells that endoplasmic reticulum stress promotes an inflammatory environment, elevating IL-6, MCP-1, and TNF-α production within adipose tissue, potentially in response to altered autophagy ( 176 , 177 ). Ageing is associated with decreased vascularisation as a result of impaired angiogenesis, supporting local hypoxia, which might drive adipose tissue macrophage accumulation ( 36 , 178 – 180 ). Ageing is also associated with reductions in the mitochondrial cytochrome c oxidase subunit 5B (COX5B) component of complex IV within adipocytes, which represses HIF-1α ( 181 ).…”

Section: Immunological Ageing and Adipose Tissuementioning

confidence: 99%

Parallels in Immunometabolic Adipose Tissue Dysfunction with Ageing and Obesity

2018

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Ageing, like obesity, is often associated with alterations in metabolic and inflammatory processes resulting in morbidity from diseases characterised by poor metabolic control, insulin insensitivity, and inflammation. Ageing populations also exhibit a decline in immune competence referred to as immunosenescence, which contributes to, or might be driven by chronic, low-grade inflammation termed “inflammageing”. In recent years, animal and human studies have started to uncover a role for immune cells within the stromal fraction of adipose tissue in driving the health complications that come with obesity, but relatively little work has been conducted in the context of immunometabolic adipose function in ageing. It is now clear that aberrant immune function within adipose tissue in obesity—including an accumulation of pro-inflammatory immune cell populations—plays a major role in the development of systemic chronic, low-grade inflammation, and limiting the function of adipocytes leading to an impaired fat handling capacity. As a consequence, these changes increase the chance of multiorgan dysfunction and disease onset. Considering the important role of the immune system in obesity-associated metabolic and inflammatory diseases, it is critically important to further understand the interplay between immunological processes and adipose tissue function, establishing whether this interaction contributes to age-associated immunometabolic dysfunction and inflammation. Therefore, the aim of this article is to summarise how the interaction between adipose tissue and the immune system changes with ageing, likely contributing to the age-associated increase in inflammatory activity and loss of metabolic control. To understand the potential mechanisms involved, parallels will be drawn to the current knowledge derived from investigations in obesity. We also highlight gaps in research and propose potential future directions based on the current evidence.

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“…Additionally, it has been shown that macrophages respond to hypoxia with changes in the production of inflammatory mediators (Trayhurn et al 2008;Lewis et al 1999). Generally, hypoxia, which is thought to be partly responsible for inflammation in obesity (Trayhurn et al 2008), might also affect the ageing process, since ageing itself is characterized by decrease in O 2 supply to tissues (Valli et al 2015).…”

Section: Ageingmentioning

confidence: 99%

Obesity and related consequences to ageing

Jura

Kozak

2016

AGE

233

165

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Obesity has become a major public health problem. Given the current increase in life expectancy, the prevalence of obesity also raises steadily among older age groups. The increase in life expectancy is often accompanied with additional years of susceptibility to chronic ill health associated with obesity in the elderly. Both obesity and ageing are conditions leading to serious health problems and increased risk for disease and death. Ageing is associated with an increase in abdominal obesity, a major contributor to insulin resistance and the metabolic syndrome. Obesity in the elderly is thus a serious concern and comprehension of the key mechanisms of ageing and age-related diseases has become a necessary matter. Here, we aimed to identify similarities underlying mechanisms related to both obesity and ageing. We bring together evidence that age-related changes in body fat distribution and metabolism might be key factors of a vicious cycle that can accelerate the ageing process and onset of age-related diseases.

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Hypoxia metabolism in ageing

Cited by 22 publications

References 7 publications

Impact of Mesenchymal Stem Cell Senescence on Inflammaging

Impact of Mesenchymal Stem Cell Senescence on Inflammaging

Parallels in Immunometabolic Adipose Tissue Dysfunction with Ageing and Obesity

Obesity and related consequences to ageing

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