ISSN 2410-7751 (Print)
ISSN 2410-776X (Online)
Biotechnologia Acta V. 18, No. 6, 2025
P. 41-57, Bibliography 70, Engl.
UDC: 004.9:612.822
doi: https://doi.org/10.15407/biotech18.06.041
HYPOXIC EFFECTS IN EXTREME STRESSFUL CONDITIONS: SOME RESEARCH TECHNOLOGIES FOR IMPROVING HEALTH AND LONGEVITY
O.M. KLYUCHKO 1, Yu.M. ONOPCHUK 2, G.V. LIZUNOV 3, K. S. LYMAN 4, A. G. LIZUNOVA 5
1 State University "Kyiv Aviation Institute", Ukraine
2 Institute of Cybernetics of V. M. Glushkov National Academy of Sciences, Kyiv, Ukraine
3 Space Research Institute of the National Academy of Sciences of Ukraine, Kyiv
4 Washington State University, USA
5 Luxoft Global Operations GmbH: Zug, CH, USA
Aim. Description of some technologies of many years of research and their results in the age aspect in extreme situations (such as hypoxia), application of these technologies to improve the survival of organisms in stressful situations, their treatment and rehabilitation, as well as longevity.
Methods. Numerous observations on changes in biometric indicators in the comparative-age aspect of individuals in extreme highland conditions using standard methods of laboratory analysis of bioindicators in mountain conditions were analyzed. The digital indicators input to databases; mathematical, program modeling were used.
Results. The data on observations and measurements of various physiological characteristics of people, presented in a comparative age aspect, are presented. The influence of high-altitude factors on the longevity of bioorganisms, as well as some problems in aging physiology and hypoxic states, is described. The results of examinations of veteran climbers regarding adaptation to hypoxic barium, active gradual (stepwise) adaptation, the hypoxic therapy method, and combinations of these methods are discussed. A mathematical model of ischemic heart disease is presented, and technologies for the survival of people of different ages under extreme, stressful conditions are developed.
Conclusion. Hypoxybaria increases an organism's resistance, protects against premature aging, and promotes longevity. With age, an organism's ability to adapt to hypoxia decreases, but is not entirely lost (older people can adapt up to 5000 m a.s.l.) The obtained results are essential for the further development of technologies for the survival of human of different ages in extreme, stressful conditions, their treatment, and rehabilitation.
Keywords: hypoxia, adaptation, extreme stressful conditions, numerical indices of physiological functions, long-livers, mathematical modeling
© Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, 2025
References
1.Ollé-Vila, A., Seoane, L. F., Solé, R. (2020). Ageing, computation and the evolution of neural regeneration processes. J.of the Royal Society Interface., 17(168), 1-10. https://doi.org/10.1098/rsif.2020.0181
- Sofiat Makanjuola-Akinola. (2021). What is the biggest benefit technology will have on ageing and longevity? Health and healthcare systems.: 2021. Updated: 2024. E-publication. https://www.weforum.org/stories/2021/03/what-is-the-biggest-benefit-technology-ageing-longevity-global-future-council-tech-for-good/
- Peng, X. Chen, Leyuan, Zhang,, Di Chen, Ye Tian.(2023). Mitochondrial stress and aging: Lessons from C. elegans. 10849521. https://doi.org/1016/j.semcdb.2023.02.010
- Quinlan, R. A., Clark, J. I. (2022). Insights into the biochemical and biophysical mechanisms mediating the longevity of the transparent optics of the eye lens. JBC 1-22. E-publication, 1-22. https://doi.org/10.1016/j.jbc.2022.102537
- Xu, , Wang, J., Guo, Z., He, Z., Shi, S. (2020). Genomic convergence in the adaptation to extreme environments. Plant Commun., 1(6), 872–879 . https://doi. org/10.1016/j.xplc.2020.100117
- Manni, , Berkeley, M. R., Seppey, M., Simão, F. A., Zdobnov, E. M. (2021). BUSCO update: novel and streamlined workflows along with broader and deeper phylogenetic coverage for scoring of eukaryotic, prokaryotic, and viral genomes. Mol. Biol. Evol., 38, 4647–4654. https://doi. org/10.1093/molbev/msab199
- Carter, S., Kingsbury, M. A. (2022). Oxytocin and oxygen: the evolution of a solution to the ‘stress of life. Philos. Trans. R. Soc. Lond. B Biol. Sci., 377(1858), 20210054. https://doi.org/10.1098/rstb.2021.0054.
- González-Buenfil, , Vieyra-Sánchez, S., Quinto-Cortés, C. D., Oppenheimer, S. J., Pomat, W., Laman, M., Cervantes- Hernández, M.C., ..., Moreno-Estrada, (2024). Genetic Signatures of Positive Selection in Human Populations Adapted to High Altitude in Papua New Guinea. Genome Biology and Evolution, 16(8), evae161. https://doi.org/10.1093/gbe/evae161
- Badran, W., Caulfield, K. A., Cox, C., Lopez, J. W., Borckardt, J. J., DeVries, W. H., Summers, P., ..., Roberts, D. R. (2020). Brain stimulation in zero gravity: transcranial magnetic stimulation (TMS) motor threshold decreases during zero gravity induced by parabolic flight. NPJ Microgravity, 6, 26. https://doi.org/10.1038/s41526-020- 00116-6
- Angeloni, D., Demontis, G.C. (2020). Endocrine adaptations across physical and psychological stressors in long-term space flights. Opin. Endocr. Metab. Res. https://doi.org/10.1016/j.coemr.2019.12.005
- Vianna, A., Fernandes, F. A. N., Frugone, M. J., Figueiró, H. V., Pertierra,
L. R., Noll, D., Bi, K., Wang-Claypool, C. Y., ..., Bowie, R. C. K. (2020). Genome- wide analyses reveal drivers of penguin diversification. Proc. Natl. Acad. Sci. USA, 117(36), 22303–22310. https://doi.org/10.1073/pnas.2006659117.
- Pham, , Parikh, K., Heinrich, E. C. (2021). Hypoxia and inflammation: insights from high-altitude physiology. Front Physiol., 12, 676782. https://doi.org/10.3389/ fphys.2021.676782.
- Cunha, C. E. X., Oliveira, A. F., Dantas, G. F. G., Castro, L. R., Vitor de Omena Jucá, J., Vieira, G. C. F., Ribeiro, M. V. M. R. (2021). Neuropsychiatric aspects of the space missions: scientific overview of the last 15 years. Physiol. Med. Rehabil. J., 6 (1), 4-9. https://doi.org/10.15406/ipmrj.2021.06.00270
- León, , Pizarro, E. J., Noll, D., Pertierra, L. R., Gonzalez, B. A., Johnson, W. E., Marín, J. C., Vianna, J. A. (2024). History of Diversification and Adaptation from North to South Revealed by Genomic Data: Guanacos from the Desert to Sub-Antarctica. Genome Biology and Evolution, 16(5), evae085, https://doi.org/10.1093/gbe/evae085
- Davis, J., Stepanak, J., Fogarty, J., Blue, R. (2021). Fundamentals of Aerospace Medicine (fourth ed.), Lippincott Williams & Wilkins.
- Ding, , Zhang, X., Zhao, X., Jing, W., Cao, Z., Li, J., Huang, Y., ..., Bing,
X. (2021). A chromosome-level genome assembly of the mandarin fish (Siniperca chuatsi). Front Genet., 12, 1–15. https://doi.org/10.3389/fgene.2021.671650
- Clément G.R., Boyle R.D., George K.A., Nelson G.A., Reschke M.F., Williams T.J., Paloski W.H. (2020). Challenges to the central nervous system during human spaceflight missions to Mars. Neurophysiol., 123, 2037–2063. https://doi.org/10.1152/jn.00476.2019
- Chaumeil, A., Mussig, A. J., Hugenholtz, P., Parks, D. H. (2020). GTDB-Tk: a toolkit to classify genomes with the genome taxonomy database. Bioinformatics, 36, 1925–1927. https://doi.org/10.1093/bioinformatics/ btz848
- Kang, D., Li, F., Kirton, E., Thomas, A., Egan, R., An, H., Wang, Z. (2019). MetaBAT 2:an adaptive binning algorithm for robust and efficient genome reconstruction from metagenome assemblies. PeerJ., 7, e7359. https://doi.org/10.7287/peerj. preprints.27522v1
- Koonin, V., Makarova, K. S., Wolf, Y. I., Krupovic, M. (2020). Evolutionary entanglement of mobile genetic elements and host defence systems: guns for hire. Nat. Rev. Genet., 21, 119–131. https://doi. org/10.1038/s41576-019-0172-9
- Meziti, , Rodriguez-R.L.M., Hatt, J. K., Peña-Gonzalez, A., Levy, K., Konstantinidis, K. T. (2021). The reliability of metagenome-assembled genomes (MAGs) in representing natural populations: Insights from comparing MAGs against isolate genomes derived from the same fecal sample. Appl. Environ. Microbiol., 87, 02593–20. https://doi.org/10.1128/AEM.02593-20
- Milewska, , Krause, K., Szalewska- Pałasz, A. (2020). The stringent response of marine bacteria–assessment of (p) ppGpp accumulation upon stress conditions. J. Appl. Genet., 6, 123–130. https://doi. org/10.1007/s13353-019-00531-w
- Tozzi,, Ahmad, M. Z., Peters, J. F.(2020). Neural computing in four spatial dimensions. Neurodyn.
- Ozerov, Y., Flajshans, M., Noreikiene, K., Vasemägi, A., Gross, R., Flajšhans, M., Noreikiene, K., ..., Gross, R. (2020). Draft genome assembly of the freshwater apex predator wels catfish (Silurus glanis) using linked-read sequencing. G3- Genes Genom Genet., 10, 3897–3906. https://doi. org/10.1534/g3.120.401711
- Di Concilio A., Guadagni C., Peters J. , Ramanna S.(2018). Descriptive proximities, properties and interplay between classical proximities and overlap.Comp. Sci., 12, 91–106. https://doi.org/10.1007/s11786-017-0328-y
- Peters J. (2020). Computational Geometry, Topology and Physics of Digital Images with Applications. Shape Complexes, Optical Vortex Nerves and Proximities. Springer Nature: Cham, Switzerland, xxv+440. https://i.twirpx.link/file/2943627/
- Barkaszi,, Takács, E., Czigler, I., Balázs, L.(2016). Extreme environment effects on cognitive functions: a longitudinal study in high altitude in Antarctica. Hum. Neurosci., 10, 331. https://doi.org/10.3389/fnhum.2016.00331
- de Arcangelis,, Herrmann, H. J.(2010). Learning as a phenomenon occurring in a critical state. Natl. Acad. Sci. USA, 107, 3977–3981. https://doi.org/10.1073/pnas.0912289107
- Setubal, C.(2021). Metagenome-assembled genomes: concepts, analogies, and challenges. Biophys. Rev., 13(6), 905–909. https://doi. org/10.1007/s12551-021-00865-y
- Muhammad Faisal Shahzad, Awudu (2020). Adaptation to extreme weather conditions and farm performance in rural Pakistan. Agricultural Systems, 180, 102772. https://doi.org/10.1016/j.agsy.2019.102772.
- Cunha, E. X., Oliveira, A. F., Dantas, G. F. G., Castro, L.R., de Omena, V., Jucá, J., Vieira, G. C. F., Ribeiro, M. V. M. R.(2021). Neuropsychiatric aspects of the space missions: scientific overview of the last 15 years. Physiol. Med. Rehabil. J., 6 (1),4-9. https://doi.org/10.15406/ipmrj.2021.06.00270
- Badran, W. , Caulfield, K. A. , Cox, C., Lopez, J. W., Borckardt, J. J., DeVries, W. H., Summers, P., Kerns, S., Hanlon, C. A., McTeague, L. M., George, M. S., Roberts, D. R. (2020). Brain stimulation in zero gravity: transcranial magnetic stimulation (TMS) motor threshold decreases during zero gravity induced by parabolic flight. NPJ Microgravity., 6, 26. https://doi.org/1038/s41526-020-00116-6
- von Wegner,, Laufs, H., Tagliazucchi, E.(2018). Mutual information identifies spurious Hurst phenomena in resting state EEG and fMRI data. Rev., 97, 022415. https://doi.org/10.1103/PhysRevE.97.022415
- Bloomberg, J. , Peters, B.T., Cohen, H.S., Mulavara, A.P.(2015). Enhancing astronaut performance using sensorimotor adaptability training. Syst. Neurosci., 9, 129. https://doi.org/10.3389/fnsys.2015.00129.
- Brainard, C., Barger, L. K., Soler, R. R., Hanifin, J. P. (2016). The development of lighting countermeasures for sleep disruption and circadian misalignment during spaceflight. Opin. Pulm. Med., 22(6), 535-544.https://doi.org/10.1097/MCP.0000000000000329.
- Clément G. , Boyle R .D., George K. A., Nelson G. A., Reschke M. F., Williams T. J., Paloski W. H.(2020). Challenges to the central nervous system during human spaceflight missions to Mars. Neurophysiol., 123, 2037-2063, https://doi.org/10.1152/jn.00476.2019
- Zubieta-Calleja, (2024). Redefining chronic mountain sickness: insights from high-altitude research and clinical experience. Medical Review, 5(1), 44–65. https://doi.org/10.1515/mr-2024-0036
- Zubieta-Calleja, , Zubieta-DeUrioste, N. (2022). High Altitude Pulmonary Edema, High Altitude Cerebral Edema, and Acute Mountain Sickness: an enhanced opinion from the High Andes — La Paz, Bolivia 3,500 m. Reviews on Environmental Health, 38(2), 327–338. https://doi.org/10.1515/ reveh-2021-0172
- Zubieta-Calleja, , Zubieta-DeUrioste, N. (2021). The oxygen transport triad in high- altitude pulmonary edema: a perspective from the high Andes. Int. J. Environ. Res. Publ. Health, 18, 7619. https://doi. org/10.3390/ijerph18147619
40. Beloshitsky P. V. Chronicle of biomedical research in Elbrus region (1929 — 2006). (2014). Ukrainian Academy of Sciences, 550 p. (In Ukrainian). URL: https://www.dovidnyk.in.ua/directories/business_kyiv/id/69790
41. Ulloa, N. A., Cook, J. (2025). Altitude-Induced Pulmonary Hypertension. StatPearls Publishing: Treasure Island, FL, USA. https://www.ncbi.nlm.nih.gov/books/NBK555925/
42. Szymczak, R. K., Marosz, M., Grzywacz, T., Sawicka, M., Naczyk, M. (2021). Death Zone Weather Extremes Mountaineers Have Experienced in Successful Ascents. Front. Physiol., 12, 998. https://doi.org/10.3389/fphys.2021.696335
43. Richalet, J. P. (2021). Adaption to chronic hypoxaemia by populations living at high altitude. In Revue des Maladies Respiratoires; Elsevier Masson s.r.l. Issy-les-Moulineaux: Paris, France, pp. 395–403 https://doi.org/10.1016/j.rmr.2020.11.007
44. Beloshitsky, P. V., Baraboy, V. A., Krasyuk, A. N., Korkach, V. I., Torbin, V. F. (1996). Postradiation rehabilitation in mountain conditions. Kyiv. 230 p. (In Ukrainian).
45. Serebrovskaya, T. V., Karaban, I. N., Kolesnikova, kaya, L. A. (2000). Geriatric Men at Altitude: Hypoxic Ventilatory Sensitivity and Blood Dopamine Changes. Respiration, 67 (3), 253–260. https://doi.org/10.1159/000029507
46. Arias-Reyes, C., Zubieta-DeUrioste, N., Poma-Machicao, L., Aliaga-Raduan, F., Carvajal-Rodriguez, F., Dutschmann, M., ..., Soliz, J. (2020). Does the pathogenesis of SARS-CoV-2 virus decrease at high-altitude? Respiratory Physiology & Neurobiology, 277, 103443. https://doi.org/10.1016/j.resp.2020.103443
47. Zubieta-Calleja, G., Zubieta-DeUrioste, N. (2021). Acute Mountain Sickness, High Altitude Pulmonary Edema, and High Altitude Cerebral Edema: A view from the High Andes. Respir Physiol. Neurobiol., 287, 103628. https://doi.org/10.1016/j.resp.2021.103628
48. Onopchuk, Yu. M., Misyura A. G. (2008) Methods of the mathematical modeling and control in theoretical studies and solution of applied problems of medicine and physiology. Sport. Meditsyna, 1, 181–188.
49. Beloshitsky, P. V., Onopchuk, Yu. M., Aralova, N.I., Semchik, T. A. (2004). Mathematic modeling of hypoxic states at heart ischemia. Physiol. J., 50(3), 139–143.
50. Beloshitsky, P. V., Onopchuk, Yu. M., Aralova, N. I. (2003). Mathematical methods for the investigation of the problem of organism functioning eliability at extreme high mountains conditions. Physiol. J., 49(3), 47–54.
51. Archer, S.L.; Sharp, W.W.; Weir, E.K. (2020). Differentiating COVID-19 Pneumonia from Acute Respiratory Distress Syndrome and High Altitude Pulmonary Edema: Therapeutic Implications. Circulation. 142(2). https://doi.org/10.1161/CIRCULATIONAHA.120.047915
52. Luks, A.M.; Swenson, E.R. (2020). COVID-19 Lung Injury and High Altitude Pulmonary Edema: A False Equation with Dangerous Implications. Ann. Am. Thorac. Soc. https://doi.org/10.1513/AnnalsATS.202004-327CME.
53. Strapazzon, G.; Hilty, M.P.; Bouzat, P.; Pratali, L.; Brugger, H.; Rauch, S. (2020). To compare the incomparable: COVID-19 pneumonia and high-altitude disease. Eur. Respir. J. https://doi.org/10.1183/13993003.01362-2020
54. Herrmann, J.; Mori, V.; Bates, J.H.T.; Suki, B. (2020). Modeling lung perfusion abnormalities to explain early COVID-19 hypoxemia. Nat. Commun. 11, 1–9. https://www.nature.com/articles/s41467-020-18672-6
55. Ren, L.L., Wang, Y.M., Wu, Z.Q., Xiang, Z.C., Guo, L., Xu, T., Jiang, Y.Z., Xiong, Y., …, Wang, J.W. (2020). Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study. Chin. Med. J. https://doi.org/10.1097/CM9.0000000000000722.
56. Van de Ville, D., Britz, J., Michel, C. M. (2020). EEG microstate sequences in healthy humans at rest reveal scale-free dynamics. Natl. Acad. Sci. USA, 107, 18179–18184. https://doi.org/10.1073/pnas.1007841107
57. Barger, L. K., Sullivan, J. P., Lockley, S. W., Czeisler, C. A. (2021). Exposure to short wavelength-enriched white light and exercise improves alertness and performance in operational NASA flight controllers working overnight shifts. Occup. Environ. Med. 2021, 63(2): 111-118, https://doi.org/10.1097/JOM.0000000000002054.
58. Brasher, K. S., Sparshott, K. F., Weir, A. B., Day, A. J., Bridger, R. S. (2021). Two-year follow-up study of stressors and occupational stress in submariners. Med., 62 (7), 563-565. https://doi.org/10.1093/occmed/kqs104.
59. Chariker, L., Shapley, R., Young, L.-S. (2018). Rhythm and Synchrony in a Cortical Network Model. J. Neurosci., 38, 8621–8634. https://doi.org/10.1523/JNEUROSCI.0675-18.2018
60. Bartone, P. T., Krueger, G. P., Bartone, G. V. (2018). Individual differences in adaptability to isolated, confined, and extreme environments. Med. Hum. Perform., 89 (6), 536-546. https://doi.org/10.3357/AMHP.4951.2018
61. Angélil, O., Stone, D., Wehner, M., Paciorek, C.J., Krishnan, H., Collins, W. (2017). An independent assessment of anthropogenic attribution statements for recent extreme temperature and rainfall events. J. Clim., 30, 5–16. https://doi.org/10.1175/ JCLI-D-16-0077.1.
62. Balza, U., Baldi, R., Rodríguez-Planes, L., Ojeda, R, Schiavini, A. (2023). Scientific evidence does not support the translocation of guanacos in Argentina. Conserv. Sci. Pract., 5(11), e13031. https://doi.org/10.1111/csp2.13031.
63. Diaz-Maroto, P., Rey-Iglesia, A., Cartajena, I., Núñez, L., Westbury, M.V., Varas, V., Moraga, M., ..., Hansen, J. (2021). Ancient DNA reveals the lost domestication history of South American camelids in Northern Chile and across the Andes. eLife, 10, e63390. https://doi.org/10.7554/eLife.63390.
64. Flores, C., Lichtenstein, G., Schiavini, A. (2023). Human–wildlife conflicts in Patagonia: ranchers’ perceptions of guanaco Lama guanicoe abundance. Oryx, 57(5), 615–625. https://doi.org/10.1017/S0030605322001508.
65. Iranzo, E. C., Smith, C., Moraga, C. A., Radic-Schilling, S., Corti, P. (2022). Patterns of guanaco distribution and microhabitat use in Tierra del Fuego: from protected to sheep ranching areas. Acta Oecol., 116, 103853. https://doi.org/10.1016/j.actao.2022.103853.
66. Mesas, A., Cuéllar-Soto, E., Romero, K., Zegers, T., Varas, V., González, B. A., Johnson, W. E., Marín, J. C. (2021). Assessing patterns of genetic diversity and connectivity among guanacos (Lama guanicoe) in the Bolivian Chaco: implications for designing management strategies. Stud. Neotrop. Fauna Environ., 58(1), 94–103 https://doi.org/10.1080/01650521.2021.1914294.
67. Mesas, A., Baldi, R., González, B. A., Burgi, V., Chávez, A., Johnson, W. E., Marín, J. C. (2021). Past and recent effects of livestock activity on the genetic diversity and population structure of native guanaco populations of arid patagonia. Animals (Basel), 11(5), 1218 . https://doi.org/10.3390/ani11051218.
68. Merchant, N. N., Ivanova, A., Hart, D. W., García, C., Bennett, N.C., Portugal, S. J., Faulkes, C. G. (2024). Patterns of Genetic Diversity and Gene Flow Associated With an Aridity Gradient in Populations of Common Mole-rats, Cryptomys hottentotus. Genome Biology and Evolution, 16(7), evae144. https://doi.org/10.1093/gbe/evae144
69. Herrera-Álvarez, S., Karlsson, E., Ryder, O. A., Lindblad-Toh, K., Crawford, A. J. (2021). How to make a rodent giant: genomic basis and tradeoffs of gigantism in the capybara, the world’s largest rodent. Mol. Biol. Evol., 38(5), 1715–1730. https://doi. org/10.1093/molbev/msaa285.
70. Bosi, E., Taviani, E., Avesani, A., Doni, L., Auguste, M., Oliveri, C., Leonessi, M., ..., Vezzulli, L. (2024). Pan-Genome Provides Insights into Vibrio Evolution and Adaptation to Hydrothermal Vents. Genome Biology and Evolution, 16(7), evae131. https://doi.org/10.1093/gbe/evae131