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The Telomere-Telomerase System Is Detrimental to Health at High-Altitude

Author

Listed:
  • Qadar Pasha

    (Council of Scientific & Industrial Research-Institute of Genomics and Integrative Biology, New Delhi 110007, India
    Institute of Hypoxia Research, New Delhi 110067, India)

  • Manjari Rain

    (Council of Scientific & Industrial Research-Institute of Genomics and Integrative Biology, New Delhi 110007, India
    Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, Uttar Pradesh, India)

  • Sana Tasnim

    (Council of Scientific & Industrial Research-Institute of Genomics and Integrative Biology, New Delhi 110007, India)

  • Hema Kanipakam

    (Council of Scientific & Industrial Research-Institute of Genomics and Integrative Biology, New Delhi 110007, India)

  • Tashi Thinlas

    (Department of Medicine, Sonam Norboo Memorial Hospital, Leh 194101, Ladakh, India)

  • Ghulam Mohammad

    (Department of Medicine, Sonam Norboo Memorial Hospital, Leh 194101, Ladakh, India)

Abstract

The hypobaric-hypoxia environment at high-altitude (HA, >2500 m) may influence DNA damage due to the production of reactive molecular species and high UV radiation. The telomere system, vital to chromosomal integrity and cellular viability, is prone to oxidative damages contributing to the severity of high-altitude disorders such as high-altitude pulmonary edema (HAPE). However, at the same time, it is suggested to sustain physical performance. This case-control study, comprising 210 HAPE-free (HAPE-f) sojourners, 183 HAPE-patients (HAPE-p) and 200 healthy highland natives (HLs) residing at ~3500 m, investigated telomere length, telomerase activity, and oxidative stress biomarkers. Fluidigm SNP genotyping screened 65 single nucleotide polymorphisms (SNPs) in 11 telomere-maintaining genes. Significance was attained at p ≤ 0.05 after adjusting for confounders and correction for multiple comparisons. Shorter telomere length, decreased telomerase activity and increased oxidative stress were observed in HAPE patients; contrarily, longer telomere length and elevated telomerase activity were observed in healthy HA natives compared to HAPE-f. Four SNPs and three haplotypes are associated with HAPE, whereas eight SNPs and nine haplotypes are associated with HA adaptation. Various gene-gene interactions and correlations between/among clinical parameters and biomarkers suggested the presence of a complex interplay underlining HAPE and HA adaptation physiology. A distinctive contribution of the telomere-telomerase system contributing to HA physiology is evident in this study. A normal telomere system may be advantageous in endurance training.

Suggested Citation

  • Qadar Pasha & Manjari Rain & Sana Tasnim & Hema Kanipakam & Tashi Thinlas & Ghulam Mohammad, 2023. "The Telomere-Telomerase System Is Detrimental to Health at High-Altitude," IJERPH, MDPI, vol. 20(3), pages 1-22, January.
    • Handle: RePEc:gam:jijerp:v:20:y:2023:i:3:p:1935-:d:1042299
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    References listed on IDEAS

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    1. Victor Barbosa Ribeiro & Daiana Cristina Chielli Pedroso & Gislaine Satyko Kogure & Iris Palma Lopes & Barbara Aparecida Santana & Hugo Celso Dutra de Souza & Rui Alberto Ferriani & Rodrigo Tocantins , 2021. "Short-Term Aerobic Exercise Did Not Change Telomere Length While It Reduced Testosterone Levels and Obesity Indexes in PCOS: A Randomized Controlled Clinical Trial Study," IJERPH, MDPI, vol. 18(21), pages 1-14, October.
    2. Diego Loayza & Titia de Lange, 2003. "POT1 as a terminal transducer of TRF1 telomere length control," Nature, Nature, vol. 423(6943), pages 1013-1018, June.
    3. Eros Lazzerini Denchi & Titia de Lange, 2007. "Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1," Nature, Nature, vol. 448(7157), pages 1068-1071, August.
    4. Huawei Xin & Dan Liu & Ma Wan & Amin Safari & Hyeung Kim & Wen Sun & Matthew S. O’Connor & Zhou Songyang, 2007. "TPP1 is a homologue of ciliate TEBP-β and interacts with POT1 to recruit telomerase," Nature, Nature, vol. 445(7127), pages 559-562, February.
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