Contribution of hypoxia to Alzheimer’s disease: is HIF-1α a mediator of neurodegeneration?

Ogunshola, Omolara O.; Antoniou, Xanthi

doi:10.1007/s00018-009-0141-0

Cited by 116 publications

(82 citation statements)

References 88 publications

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“…Many other age-related diseases, including Alzheimer’s disease, Parkinson’s disease, and diabetes, involve hypoxic conditions that can worsen the disease. Studies examining Aβ accumulation in Alzheimer’s disease suggest that increased HIF-1α tends to be protective in disease free states, but that increased HIF-1α levels are also a sign of advanced disease progression (Ogunshola & Antoniou 2009). This seemingly contradictory data may stem from the role of HIF-1α in stress response, in that its up-regulation can be either protective or reactive in nature, and the context of measurement is important (Ogunshola & Antoniou 2009).…”

Section: A Role For Hif In Mammalian Aging?mentioning

confidence: 99%

The hypoxia-inducible factor HIF-1 functions as both a positive and negative modulator of aging

Leiser

Kaeberlein

2010

Biological Chemistry

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In the past year and a half, five studies have independently established a direct connection between the hypoxic response transcription factor, HIF-1, and aging in Caenorhabditis elegans. These studies demonstrated that HIF-1 can both promote and limit longevity via pathways that are mechanistically distinct. Here we review the current state of knowledge regarding modulation of aging by HIF-1 and speculate on potential aspects of HIF-1 function that may be relevant for mammalian longevity and healthspan.

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Section: A Role For Hif In Mammalian Aging?mentioning

confidence: 99%

The hypoxia-inducible factor HIF-1 functions as both a positive and negative modulator of aging

Leiser

Kaeberlein

2010

Biological Chemistry

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“…Oxidative stress and hypoxia are known to occur in a variety of tissues during aging (4,12,13,47,56,58,65,67), although current studies have not defined whether these events occur in subcutaneous and visceral fat depots during aging. Both oxidative stress and hypoxia are known to occur in adipose tissue in response to diet-induced obesity as well as in genetic models of obesity (53,62,63,70,72).…”

mentioning

confidence: 97%

Aging is associated with hypoxia and oxidative stress in adipose tissue: implications for adipose function

Zhang

Ebenezer

Dasuri

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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As a part of aging there are known to be numerous alterations which occur in multiple tissues of the body, and the focus of this study was to determine the extent to which oxidative stress and hypoxia occur during adipose tissue aging. In our studies we demonstrate for the first time that aging is associated with both hypoxia (38% reduction in oxygen levels, Po2 21.7 mmHg) and increases reactive oxygen species in visceral fat depots of aging male C57Bl/6 mice. Interestingly, aging visceral fat depots were observed to have significantly less change in the expression of genes involved in redox regulation compared with aging subcutaneous fat tissue. Exposure of 3T3-L1 adipocytes to the levels of hypoxia observed in aging adipose tissue was sufficient to alter multiple aspects of adipose biology inducing increased levels of in insulin-stimulated glucose uptake and decreased lipid content. Taken together, these data demonstrate that hypoxia and increased levels of reactive oxygen species occur in aging adipose tissue, highlighting the potential for these two stressors as potential modulators of adipose dysfunction during aging.

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“…Oxygen levels lower than ambient (10 kPa O 2 ) have been known since the 1970s to increase the replicative lifespan of cultured human cells (Packer & Fuehr, 1977). Furthermore, low oxygen levels have been shown to be important for stem cell maintenance, and many immortalized tumor lines show low rates of oxygen consumption and high rates of glycolysis (Fehrer et al, 2007).…”

Section: Hypoxiamentioning

confidence: 98%

Oxygen and Aging

Pitt¹,

Leiser²,

Kaeberlein³

2014

annu rev gerontol geriatr

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Oxygen is a double-edged sword. Despite the near universal requirement for oxygen for survival and reproduction in animals, oxygen and oxidative metabolism are responsible for the production of reactive oxygen species (ROS), which has, until recently, been considered a cellular toxin and a major cause of aging. Alterations in environmental oxygen can alter rates of aging and ROS production in many organisms. Animals coordinate the cellular response to low oxygen with a conserved hypoxic response mediated by the hypoxia inducible transcription factor, hypoxia-inducible factor (HIF). In addition to hypoxia, HIF has been shown to have roles in aging, cancer, cardiovascular disease, and stem cell maintenance in organisms from worms to humans. Furthermore, HIF has been shown to interact with mechanistic target of rapamycin (mTOR), Sirtuins, and to infl uence other pathways and interventions known to affect the aging. This chapter focuses on the effects of altered oxygen concentrations on the aging, its similarities to dietary restriction, how mutations in the HIF pathway affect lifespan and health span, and how the HIF pathway interacts with other conserved longevity pathways.

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Contribution of hypoxia to Alzheimer’s disease: is HIF-1α a mediator of neurodegeneration?

Cited by 116 publications

References 88 publications

The hypoxia-inducible factor HIF-1 functions as both a positive and negative modulator of aging

The hypoxia-inducible factor HIF-1 functions as both a positive and negative modulator of aging

Aging is associated with hypoxia and oxidative stress in adipose tissue: implications for adipose function

Oxygen and Aging

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