Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells : a prospective trial

Hachmo, Yafit; Hadanny, Amir; Hamed, Ramzia Abu; Daniel-Kotovsky, Malka; Catalogna, Merav; Fishlev, Gregory; Lang, Erez; Polak, Nir; Doenyas, Keren; Friedman, Mony; Zemel, Yonatan; Bechor, Yair; Efrati, Shai

doi:10.18632/aging.202188

Cited by 47 publications

(56 citation statements)

References 47 publications

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“…However, erythrocytes are the main component of blood and have a unique function to deliver O 2 to every single cell within our body. Recently, a new study revealed that hyperbaric oxygen treatments (HBOTs) have a beneficial role in counteracting aging of blood cells and even reverse the aging process in healthy aging adults [71]. These studies support our work presented here that erythrocytes have a significant role to counteract aging and that hypoxia is an underestimated key factor promoting aging and function decline.…”

Section: Novelty and Significancesupporting

confidence: 81%

Erythrocyte adenosine A2B receptor prevents cognitive and auditory dysfunction by promoting hypoxic and metabolic reprogramming

et al. 2021

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Hypoxia drives aging and promotes age-related cognition and hearing functional decline. Despite the role of erythrocytes in oxygen (O2) transport, their role in the onset of aging and age-related cognitive decline and hearing loss (HL) remains undetermined. Recent studies revealed that signaling through the erythrocyte adenosine A2B receptor (ADORA2B) promotes O2 release to counteract hypoxia at high altitude. However, nothing is known about a role for erythrocyte ADORA2B in age-related functional decline. Here, we report that loss of murine erythrocyte–specific ADORA2B (eAdora2b−/−) accelerates early onset of age-related impairments in spatial learning, memory, and hearing ability. eAdora2b-/- mice display the early aging-like cellular and molecular features including the proliferation and activation of microglia and macrophages, elevation of pro-inflammatory cytokines, and attenuation of hypoxia-induced glycolytic gene expression to counteract hypoxia in the hippocampus (HIP), cortex, or cochlea. Hypoxia sufficiently accelerates early onset of cognitive and cochlear functional decline and inflammatory response in eAdora2b−/− mice. Mechanistically, erythrocyte ADORA2B-mediated activation of AMP-activated protein kinase (AMPK) and bisphosphoglycerate mutase (BPGM) promotes hypoxic and metabolic reprogramming to enhance production of 2,3-bisphosphoglycerate (2,3-BPG), an erythrocyte-specific metabolite triggering O2 delivery. Significantly, this finding led us to further discover that murine erythroblast ADORA2B and BPGM mRNA levels and erythrocyte BPGM activity are reduced during normal aging. Overall, we determined that erythrocyte ADORA2B–BPGM axis is a key component for anti-aging and anti-age–related functional decline.

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Section: Novelty and Significancesupporting

confidence: 81%

Erythrocyte adenosine A2B receptor prevents cognitive and auditory dysfunction by promoting hypoxic and metabolic reprogramming

et al. 2021

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“…Intermittent low level oxidative stresses (such as physical activity) are known to increase antioxidant protection in the presence of oxidative stress induced through bouts of acute exercise [ 39 ]. Similarly, repeated sessions of hyperbaric oxygen therapy, even inducing an oxidative stress, have been reported to be beneficial to different health parameters and associated with a significant increase in HIF [ 40 ]. Interestingly, the same reactions on telomeres can be elicited by very high or moderate exposure to high oxygen [ 40 , 41 , 42 ], suggesting that more research is needed on this topic.…”

Section: Discussionmentioning

confidence: 99%

“…In order to optimize useful clinical protocols from this paradigm, future studies are expected to focus also on “down-stream” effects of HIF-1α transcriptional activation. Depending on the therapeutic target, using MH may be more desirable [ 16 , 30 ] or, on the other hand, eliciting an oxidative stress by means of HH/VHH administration may be considered a more desirable effect [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Increasing Oxygen Partial Pressures Induce a Distinct Transcriptional Response in Human PBMC: A Pilot Study on the “Normobaric Oxygen Paradox”

Fratantonio

Virgili²,

Zucchi

et al. 2021

IJMS

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The term “normobaric oxygen paradox” (NOP), describes the response to the return to normoxia after a hyperoxic event, sensed by tissues as oxygen shortage, and resulting in up-regulation of the Hypoxia-inducible factor 1α (HIF-1α) transcription factor activity. The molecular characteristics of this response have not been yet fully characterized. Herein, we report the activation time trend of oxygen-sensitive transcription factors in human peripheral blood mononuclear cells (PBMCs) obtained from healthy subjects after one hour of exposure to mild (MH), high (HH) and very high (VHH) hyperoxia, corresponding to 30%, 100%, 140% O2, respectively. Our observations confirm that MH is perceived as a hypoxic stress, characterized by the activation of HIF-1α and Nuclear factor (erythroid-derived 2)-like 2 (NRF2), but not Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB). Conversely, HH is associated to a progressive loss of NOP response and to an increase in oxidative stress leading to NRF2 and NF-kB activation, accompanied by the synthesis of glutathione (GSH). After VHH, HIF-1α activation is totally absent and oxidative stress response, accompanied by NF-κB activation, is prevalent. Intracellular GSH and Matrix metallopeptidase 9 (MMP-9) plasma levels parallel the transcription factors activation pattern and remain elevated throughout the observation time. In conclusion, our study confirms that, in vivo, the return to normoxia after MH is sensed as a hypoxic trigger characterized by HIF-1α activation. On the contrary, HH and VHH induce a shift toward an oxidative stress response, characterized by NRF2 and NF-κB activation in the first 24 h post exposure.

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“…A hypoxic environment created by the accumulation of adenosine and cAMP was reported to induce T cell senescence [14] . A prospective trial showed that hyperbaric oxygen therapy increases telomere length in peripheral blood cells and decreases the number of senescent T cells [98] . Similarly, physical exercise, which can increase the amount of oxygen in the blood, prevents cellular senescence in circulating leukocytes [99] .…”

Section: Senescent T Cells As Therapeutic Targetsmentioning

confidence: 99%

Senescent T cells: a potential biomarker and target for cancer therapy

Zhang

Xue

et al. 2021

EBioMedicine

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The failure of T cells to eradicate tumour cells in the tumour microenvironment is mainly due to the dysfunction of T cells. Senescent T cells, with defects in proliferation and effector functions, accumulate in ageing, chronic viral infections, and autoimmune disorders where antigen stimulation persists. Increasing evidence suggests that inducing T cell senescence is a key strategy used by malignant tumours to evade immune surveillance. In this review, we summarize the general features, functional regulation, and signalling network of senescent T cells in tumour development and highlight their potential as prognostic biomarkers in multiple cancer treatments, including chemotherapy, radiotherapy, and immunotherapy. Moreover, we discuss possible therapeutic strategies for preventing or rejuvenating senescence in tumour-specific T cells. Understanding these critical issues may provide novel strategies to enhance cancer immunotherapy.

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Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells : a prospective trial

Cited by 47 publications

References 47 publications

Erythrocyte adenosine A2B receptor prevents cognitive and auditory dysfunction by promoting hypoxic and metabolic reprogramming

Erythrocyte adenosine A2B receptor prevents cognitive and auditory dysfunction by promoting hypoxic and metabolic reprogramming

Increasing Oxygen Partial Pressures Induce a Distinct Transcriptional Response in Human PBMC: A Pilot Study on the “Normobaric Oxygen Paradox”

Senescent T cells: a potential biomarker and target for cancer therapy

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