Telomere elongation protects heart and lung tissue cells from fatal damage in rats exposed to severe hypoxia

Abstract

BackgroundThe effects of acute hypoxia at high altitude on the telomere length of the cells in the heart and lung tissues remain unclear. This study aimed to investigate the change in telomere length of rat heart and lung tissue cells in response to acute exposure to severe hypoxia and its role in hypoxia-induced damage to heart and lung tissues.MethodsForty male Wistar rats (6-week old) were randomized into control group (n = 10) and hypoxia group (n = 30). Rats in control group were kept at an altitude of 1500 m, while rats in hypoxia group were exposed to simulated hypoxia with an altitude of 5000 m in a low-pressure oxygen chamber for 1, 3, and 7 days (n = 10). The left ventricular and right middle lobe tissues of each rat were collected for measurement of telomere length and reactive oxygen species (ROS) content, and the mRNA and protein levels of telomerase reverse transcriptase (TERT), hypoxia-inducible factor1α (HIF-1α), and hypoxia-inducible factor1α (HIF-2α).ResultsIncreased exposure to hypoxia damaged rat heart and lung tissue cells and increased ROS production and telomere length. The mRNA and protein levels of TERT and HIF-1α were significantly higher in rats exposed to hypoxia and increased with prolonged exposure; mRNA and protein levels of HIF-2α increased only in rats exposed to hypoxia for 7 days. TERT was positively correlated with telomere length and the levels of HIF-1α but not HIF-2α.ConclusionsAcute exposure to severe hypoxia causes damage to heart and lung tissues due to the production of ROS but promotes telomere length and adaptive response by upregulating TERT and HIF-1α, which protect heart and lung tissue cells from fatal damage.

Growth differentiation factor 11 attenuates cardiac ischemia reperfusion injury via enhancing mitochondrial biogenesis and telomerase activity

“…We noted that in addition to inhibiting apoptosis by alleviating mitochondrial damage, GDF11 suppressed apoptosis by inhibiting the proapoptotic P53/Bax pathway [ 20 , 53 ] and promoting the antiapoptotic PI3K/Akt/FoxO3a signaling pathway through activation of telomerase. Consistently, it has been reported that an increase in TL resulting from upregulation of telomerase can protect the heart from fatal damage by severe anoxia [ 54 ], while TERT represses the expression of tumor necrosis factor-related apoptotic genes, B-cell lymphoma 2 (BCL2) and P53 [ 55 ]. These data suggest that inhibition of telomerase may aggravate apoptosis by promoting the release of proapoptotic factors, and inhibiting antiapoptotic factors in both mitochondrial-dependent and mitochondrial-independent pathways.…”

Chromosomal Processes in Mind-Body Medicine: Chronic Stress, Cell Aging, and Telomere Length

“…Using yeast as a model organism, it has been shown that stressors and noxae can have very different outcomes: alcohol and acetic acid elongate telomeres, whereas caffeine and high temperatures shorten telomeres [ 17 ]. In addition, acute exposure to severe hypoxia in rats has been demonstrated to cause damage to heart and lung tissues due to the production of reactive oxygen species (i.e., oxidative stress), but at the same time, and perhaps counterintuitively, to promote telomere length and adaptive responses by upregulating mRNA and protein levels of telomerase reverse transcriptase (TERT) [ 18 ]. By combining genome-wide expression measurements with a systematic genetic screen, the Rap1/Rif1 pathway has been identified as a central mediator of the telomeric response to environmental signals [ 17 ].…”

Effects of Intermittent Hypoxia in Training Regimes and in Obstructive Sleep Apnea on Aging Biomarkers and Age-Related Diseases: A Systematic Review

“…When children or younger people suffer from OSA, telomere shortening is not pronounced. High altitude hypoxia (5,000 m) causes both tissue damage due to oxidative stress and telomere elongation due to HIF-1α-TERT axis activation ( Wang et al, 2018 ). Physical exercise, which is always accompanied by moderate intermittent hypoxia, increases TL in older persons ( Sánchez-González et al, 2021 ; Sellami et al, 2021 ); it can be speculated that when intermittent hypoxia is applied in a training regime, oxidative stress is minimal; an increase in telomerase expression would lead to telomeres elongation, thereby increasing rejuvenation.…”