Beyond enabling survival in extreme environments, tardigrades open new avenues for innovation across scientific fields. This review examines the physiological and molecular mechanisms underlying tardigrade tolerance, namely cryptobiosis, damage-suppressor proteins, intrinsically disordered proteins, trehalose accumulation, and robust DNA repair pathways. Furthermore, it highlights their potential applications in cryopreservation, radioprotection, astrobiology, biotechnology, and medicine. In cryobiology, tardigrade-derived molecules offer strategies to improve the viability of cells, tissues, and organs during freezing and thawing. Their natural radioprotective mechanisms may inform the development of novel cancer therapies and advanced shielding materials. Insights into tardigrade survival in the vacuum of space provide valuable models for life-support systems and planetary protection in long-duration missions. Moreover, engineering tardigrade proteins into microbial or human cells holds promise for enhanced stress tolerance in industrial bioprocessing and therapeutic contexts. By unravelling these unique survival strategies, researchers can leverage tardigrades as a blueprint for designing next-generation solutions to pressing challenges in human health, food security, and space exploration.
MillerWR. Tardigrades. Am Sci, 2011; 99(5):384–391; doi: 10.1511/2011.92.384
2.
HashimotoT, KuniedaT. DNA protection protein, a novel mechanism of radiation tolerance: Lessons from tardigrades. Life (Basel), 2017; 7(2):26; doi: 10.3390/LIFE7020026
3.
MøbjergN, HalbergKA, JørgensenA, et al.Survival in extreme environments—on the current knowledge of adaptations in tardigrades. Acta Physiol (Oxf), 2011; 202(3):409–420; doi: 10.1111/J.1748-1716.2011.02252.X
4.
HagelbäckP, JönssonKI. An experimental study on tolerance to hypoxia in tardigrades. Front Physiol, 2023; 14:1249773; doi: 10.3389/fphys.2023.1249773
5.
McgrathC, Eyre-WalkerA, KatzLA. Highlight: Tardigrades and the Science of Extreme Survival. Genome Biol Evol, 2024; 16(1):evad234; doi: 10.1093/GBE/EVAD234
6.
Romano IFA. ON WATER BEARS. Fla Entomol, 2003; 86(2):134–137.
7.
RahmPG. Die Trockenstarre (Anabiose) Der Moorstierwelt (Ihr Verlauf, Ihre Bedeutung Und Ihr Unterschied von Der Cystenbildung).1926.
8.
RahmPG. Weitere physiologische Versuche mit niederen Temperaturen. Ein Beitrag zur Lösung des Kalteproblems. Verh Dtsch Zool Ges, 1924; 29:106–111.
9.
RahmPG. Biologische und physiologische Beitrage zur Kenntnis de Moosfauna. Z. allgem. Physiol, 1921; 20:1–35.
10.
BecquerelP. La Suspension de La Vie Au-Dessous de 1/20 K Absolu Par Demagnetization Adiabatique de l’alun de Fer Dans Le Vide Les plus Eléve CR Seances Acad. 1950.
HorikawaDD. Survival of Tardigrades in Extreme Environments: A Model Animal for Astrobiology BT. Anoxia: Evidence for Eukaryote Survival and Paleontological Strategies. (AltenbachA V, BernhardJM, Seckbach J. eds) Springer Netherlands: Dordrecht; 2012; pp. 205–217; doi: 10.1007/978-94-007-1896-8_12
13.
HorikawaDD, SakashitaT, KatagiriC, et al.Radiation tolerance in the tardigrade Milnesium tardigradum. Int J Radiat Biol, 2006; 82(12):843–848; doi: 10.1080/09553000600972956
14.
KasianchukN, RzymskiP, KaczmarekŁ. The biomedical potential of tardigrade proteins: A review. Biomed Pharmacother, 2023; 158:114063; doi: 10.1016/J.BIOPHA.2022.114063
15.
RichardsAB, KrakowkaS, DexterLB, et al.Trehalose: A review of properties, history of use and human tolerance, and results of multiple safety studies. Food Chem Toxicol, 2002; 40(7):871–898; doi: 10.1016/S0278-6915(02)00011-X
16.
CroweJH. Trehalose As a “Chemical Chaperone.” In: Molecular Aspects of the Stress Response: Chaperones, Membranes and Networks. (CsermelyP, VíghL. eds) Springer New York: New York, NY; 2007; pp. 143–158.
17.
LiuQ, XuL, JiaoS, et al.Trehalose inhibited the phagocytosis of refrigerated platelets in vitro via preventing apoptosis. Transfusion (Paris), 2009; 49(10):2158–2166; doi: 10.1111/j.1537-2995.2009.02254.x
18.
Novotná FloriančičováK, BaltzisA, SmejkalJ, et al.Phylogenetic and functional characterization of water bears (Tardigrada) tubulins. Sci Rep, 2023; 13(1):5194–5113; doi: 10.1038/s41598-023-31992-z
19.
TsujimotoM, ImuraS, KandaH. Recovery and reproduction of an Antarctic tardigrade retrieved from a moss sample frozen for over 30 years. Cryobiology, 2016; 72(1):78–81.
WeronikaE, ŁukaszK. Tardigrades in Space Research - Past and Future. Orig Life Evol Biosph, 2017; 47(4):545–553; doi: 10.1007/s11084-016-9522-1
22.
GUIDETTI PDR. Actual Checklist of Tardigrada Species (2009–2025). University of Modena and Reggio Emilia; 2025.; doi: 10.25431/11380_1178608
23.
HengherrS, BrümmerF, SchillRO. Anhydrobiosis in tardigrades and its effects on longevity traits. J Zool, 2008; 275(3):216–220.
24.
RoszkowskaM, GołdynB, WojciechowskaD, et al.How long can tardigrades survive in the anhydrobiotic state? A search for tardigrade anhydrobiosis patterns. PLoS One, 2023; 18(1):e0270386; doi: 10.1371/journal.pone.0270386
25.
NagwaniAK, MelosikI, KaczmarekŁ, et al.Recovery from anhydrobiosis in the tardigrade Paramacrobiotus experimentalis: Better to be young than old and in a group than alone. Heliyon, 2024; 10(5):e26807; doi: 10.1016/j.heliyon.2024.e26807
26.
GuidettiR, AltieroT, RebecchiL. On dormancy strategies in tardigrades. J Insect Physiol, 2011; 57(5):567–576; doi: 10.1016/J.JINSPHYS.2011.03.003
27.
GuidettiR. Evolution of egg deposition strategies, exaptations of exuvia, and thanatochresis in tardigrades. Org Divers Evol, 2025; 25(1):3–12; doi: 10.1007/s13127-024-00642-1
28.
HandSC, DenlingerDL, PodrabskyJE, et al.Mechanisms of animal diapause: Recent developments from nematodes, crustaceans, insects, and fish. Am J Physiol Regul Integr Comp Physiol, 2016; 310(11):R1193–R1211; doi: 10.1152/AJPREGU.00250.2015/ASSET/IMAGES/LARGE/ZH60111690240009.JPEG
29.
GuidettiR, BoschiniD, AltieroT, et al.Diapause in tardigrades: A study of factors involved in encystment. J Exp Biol, 2008; 211(Pt 14):2296–2302; doi: 10.1242/JEB.015131
30.
BertolaniR, GuidettiR, JönssonI, et al.Experiences with dormancy in tardigrades. J Limnol, 2004; 63(1s):16–25; doi: 10.4081/jlimnol.2004.s1.16
31.
WomersleyC, SmithL. Anhydrobiosis in nematodes. I. The role of glycerol myo-inositol and trehalose during desiccation. 1981; 70(3):579–586.
32.
SmythersAL, JosephKM, O’DellHM, et al.Chemobiosis reveals tardigrade tun formation is dependent on reversible cysteine oxidation. PLoS One, 2024; 19(1):e0295062; doi: 10.1371/JOURNAL.PONE.0295062
33.
HvidepilLKB, MøbjergN. New insights into osmobiosis and chemobiosis in tardigrades. Front Physiol, 2023; 14:1274522.
34.
AnoudM, DelagoutteE, HelleuQ, et al.Comparative transcriptomics reveal a novel tardigrade-specific DNA-binding protein induced in response to ionizing radiation. Elife, 2024; 13:RP92621; doi: 10.7554/eLife.92621
35.
ChavezC, Cruz-BecerraG, FeiJ, et al.The tardigrade damage suppressor protein binds to nucleosomes and protects DNA from hydroxyl radicals. Elife, 2019; 8:e47682; doi: 10.7554/eLife.47682
36.
WestoverC, NajjarD, MeydanC, et al.Multi-OMICS analysis of dsup expressing human cells reveals open chromatin architectural dynamics underyling radioprotection. 2020; doi: 10.1101/2020.11.10.373571
Del CasinoC, ContiV, LicataS, et al.Mitigation of UV-B radiation stress in tobacco pollen by expression of the tardigrade damage suppressor protein (Dsup). Cells, 2024; 13(10):840; doi: 10.3390/CELLS13100840
39.
HibshmanJD, CleggJS, GoldsteinB. Mechanisms of desiccation tolerance: Themes and variations in brine shrimp, roundworms, and tardigrades. Front Physiol, 2020; 11:592016; doi: 10.3389/fphys.2020.592016
40.
MayRM. Action différentielle des rayons x et ultraviolets sur le tardigrade Macrobiotus areolatus, a l’état actif et desséché. Bull Biol Fr Belg, 1964; 98:349–367.
41.
RebecchiL, AltieroT, GuidettiR, et al.Tardigrade Resistance to Space Effects: First Results of Experiments on the LIFE-TARSE Mission on FOTON-M3 (September 2007). Astrobiology, 2009; 9(6):581–591; doi: 10.1089/ast.2008.0305
42.
JönssonKI, RabbowE, SchillRO, et al.Tardigrades survive exposure to space in low Earth orbit. Curr Biol, 2008; 18(17):R729–R731; doi: 10.1016/j.cub.2008.06.048
43.
JönssonKI. Radiation Tolerance in Tardigrades: Current Knowledge and Potential Applications in Medicine. Cancers (Basel), 2019; 11(9):1333; doi: 10.3390/CANCERS11091333
44.
JönssonKI, SchillRO, RabbowE, et al.The fate of the TARDIS offspring: No intergenerational effects of space exposure. Zool J Linn Soc, 2016; 178(4):924–930.
45.
PerssonD, HalbergKA, JørgensenA, et al.Extreme stress tolerance in tardigrades: Surviving space conditions in low earth orbit. Journal of Zoological Systematics and Evolutionary Research, 2011; 49(s1):90–97; doi: 10.1111/j.1439-0469.2010.00605.x
46.
HorikawaDD, CumbersJ, SakakibaraI, et al.Analysis of DNA repair and protection in the Tardigrade Ramazzottius varieornatus and Hypsibius dujardini after exposure to UVC radiation. PLoS One, 2013; 8(6):e64793; doi: 10.1371/journal.pone.0064793
47.
GundersenK. Beyond the tardigrades affair: Planetary protection, cospar, and the future of private space regulation. International Law and Politics, 2021; 53:871–917.
48.
HazenTC, LiD, JuF, et al.Use of microorganisms in the recovery of oil from recalcitrant oil reservoirs: Current state of knowledge, technological advances and future perspectives. Front Microbiol, 2020; 10:2996; doi: 10.3389/FMICB.2019.02996
49.
MalozyomovBV, MartyushevNV, KukartsevVV, et al.Overview of methods for enhanced oil recovery from conventional and unconventional reservoirs. Energies (Basel), 2023; 16(13):4907; doi: 10.3390/EN16134907
50.
NmegbuC, GodwinJ, KelechukwuCG, LezorK-UM. Application of aluminium and iron oxides nanoparticles and tardigrade-based microbial enhanced oil recovery (MEOR). International Journal of Engineering Research & Technology, 2023; 12(1); doi: 10.17577/IJERTV12IS010128
51.
PalS, SequeiraJS, JoshiDM, et al.Bioindicators in Heavy Metal Detection. 2023.
52.
VecchiM, Kossi AdakpoL, DunnRR, et al.The toughest animals of the Earth versus global warming: Effects of long‐term experimental warming on tardigrade community structure of a temperate deciduous forest. Ecol Evol, 2021; 11(14):9856–9863; doi: 10.1002/ECE3.7816
53.
OlatoregunA. Investigating the Detoxification of Cadmium by the Tardigrade Hypsibius Exemplaris. 2021.
54.
HygumTL, FobianD, KamilariM, et al.Comparative Investigation of Copper Tolerance and Identification of Putative Tolerance Related Genes in Tardigrades. Front Physiol, 2017; 8:95; doi: 10.3389/fphys.2017.00095
55.
KatoS, DeguchiK, ObanaM, et al.Metabolite phosphatase from anhydrobiotic tardigrades. Febs J, 2024; 291(23):5195–5213; doi: 10.1111/febs.17296
56.
Jakubowska-KrepskaN, GołdynB, Krzemińska-WowkP, et al.View of Tardigrades as potential bioindicators in biological wastewater treatment plants. Eur J Ecol, 2019; 4(2):124–130; doi: 10.2478/eje-2018-0019
57.
VarghaB, OtvösE, TubaZ. Investigations on ecological effects of heavy metal pollution in Hungary by moss-dwelling water bears (Tardigrada), as bioindicators. Ann Agric Environ Med, 2002; 9(2):141–146.
58.
SobczykM, MichnoK, KosztyłaP, et al.Tolerance to ammonia of Thulinius ruffoi (Bertolani, 1981), a tardigrade isolated from a sewage treatment plant. Bull Environ Contam Toxicol, 2015; 95(6):721–727.
59.
GuilN, HortalJ, Sánchez-MorenoS, et al.Effects of macro and micro-environmental factors on the species richness of terrestrial tardigrade assemblages in an Iberian mountain environment. Landscape Ecol, 2009; 24(3):375–390; doi: 10.1007/s10980-008-9312-x
60.
MøbjergA, KodamaM, Ramos-MadrigalJ, et al.Extreme freeze-tolerance in cryophilic tardigrades relies on controlled ice formation but does not involve significant change in transcription. Comp Biochem Physiol A Mol Integr Physiol, 2022; 271:111245; doi: 10.1016/j.cbpa.2022.111245
61.
Clark-HachtelCM, HibshmanJD, De BuysscherT, et al.The tardigrade Hypsibius exemplaris dramatically upregulates DNA repair pathway genes in response to ionizing radiation. Curr Biol, 2024; 34(9):1819–1830.e6; doi: 10.1016/j.cub.2024.03.019
62.
LiL, GeZ, LiuS, et al.Multi-omics landscape and molecular basis of radiation tolerance in a tardigrade. Science, 20242025;386(6720):eadl0799; doi: 10.1126/science.adl0799
63.
KirtaneAR, BiJ, RajeshNU, et al.Radioprotection of healthy tissue via nanoparticle-delivered mRNA encoding for a damage-suppressor protein found in tardigrades. Nat Biomed Eng, 2025 2025;9(8):1240–1253; doi: 10.1038/s41551-025-01360-5
64.
ZarubinM, MurugovaT, RyzhykauY, et al.Structural study of the intrinsically disordered tardigrade damage suppressor protein (Dsup) and its complex with DNA. Sci Rep, 2024; 14(1):22910; doi: 10.1038/s41598-024-74335-2
65.
HashimotoT, HorikawaDD, SaitoY, et al.Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein. Nat Commun, 2016; 7(1):12808–12814; doi: 10.1038/ncomms12808
66.
ChenF-D, ZhangB, WangL-L, et al.DSUP modified mesenchymal stem cells exert significant radiation protective effect by enhancing the hematopoietic niche. Stem Cell Res Ther, 2025; 16(1):216; doi: 10.1186/s13287-025-04300-x
67.
WestoverC, NajjarD, MeydanC, et al.Engineering Radioprotective Human Cells Using the Tardigrade Damage Suppressor Protein. DSUP, 2020; 50:51.
68.
TylerJ, AguilarR, ArslanovicN, et al.Multivalent Binding of the Tardigrade Dsup Protein to Chromatin Promotes Yeast Survival and Longevity upon Exposure to Oxidative Damage. Res Sq, 2023:28:rs.3.rs–3182883; doi: 10.21203/rs.3.rs-3182883/v1
69.
HesgroveC, BoothbyTC. The biology of tardigrade disordered proteins in extreme stress tolerance. Cell Commun Signal, 2020; 18(1):178; doi: 10.1186/S12964-020-00670-2
70.
EicherJE, BromJA, WangS, et al.Secondary structure and stability of a gel-forming tardigrade desiccation-tolerance protein. Protein Sci, 2022; 31(12):e4495; doi: 10.1002/pro.4495
71.
ZarubinM, AzorskayaT, KuldoshinaO, et al.The tardigrade Dsup protein enhances radioresistance in Drosophila melanogaster and acts as an unspecific repressor of transcription. iScience, 2023; 26(7):106998; doi: 10.1016/j.isci.2023.106998
72.
PoughJD, WolyniakMJ. Characterization of DNA damage suppression from the tardigrade (Ramazzottius varieornatus) gene Dsup in E. coli through ultraviolet radiation and hydrogen peroxide exposure. The FASEB Journal, 2019; 33(S1); doi: 10.1096/fasebj.2019.33.1_supplement.457.19
73.
ChenA, TapiaH, GoddardJM, et al.Trehalose and its applications in the food industry. Compr Rev Food Sci Food Saf, 2022; 21(6):5004–5037; doi: /10.1111/1541-4337.13048
74.
CroweJH, MadinKA. Anhydrobiosis in Tardigrades and Nematodes. Trans Am Microsc Soc, 1974; 93(4):513; doi: 10.2307/3225155
75.
OhtakeS, WangYJ. Trehalose: Current use and future applications. J Pharm Sci, 2011; 100(6):2020–2053; doi: 10.1002/jps.22458
76.
LimS, ReillyCB, BarghoutiZ, et al.Tardigrade secretory proteins protect biological structures from desiccation. Communications Biology, 2024; 7(1):1–10; doi: 10.1038/s42003-024-06336-w
77.
BoothbyTC, TapiaH, BrozenaAH, et al.tardigrades use intrinsically disordered proteins to survive desiccation. Mol Cell, 2017; 65(6):975–984.e5; doi: 10.1016/j.molcel.2017.02.018
78.
WireduC. Investigating the role of tardigrade intrinsically disordered proteins in desiccation tolerance. 2023.
79.
Sanchez-MartinezS, RamirezJF, MeeseEK, et al.The tardigrade protein CAHS D interacts with, but does not retain, water in hydrated and desiccated systems. Sci Rep, 2023; 13(1):10449; doi: 10.1038/S41598-023-37485-3
80.
KanojiaG, Have R, SoemaPC, et al.Developments in the formulation and delivery of spray dried vaccines. Hum Vaccin Immunother, 2017; 13(10):2364–2378; doi: 10.1080/21645515.2017.1356952
81.
AfreenS, AnisB. Biology, Adaptability, and The Economic Applications ofTardigrades In Future. Journal of Science and Technology, 2020; 6(1):109–117; doi: 10.46243/jst.2021.v6.i1.pp109-117
82.
ŠatkauskienėI. Tardigrades (Tardigrada) in baltic states. Biologija, 2013; 58(4); doi: 10.6001/biologija.v58i4.2600
83.
TonioloSP, AfkhamiS, D’AgostinoMR, et al.Spray dried VSV-vectored vaccine is thermally stable and immunologically active in vivo. Sci Rep, 2020; 10(1):13349; doi: 10.1038/S41598-020-70325-2
84.
PackebushMH, Sanchez-MartinezS, BiswasS, et al.Natural and engineered mediators of desiccation tolerance stabilize Human Blood Clotting Factor VIII in a dry state. Sci Rep, 2023; 13(1):4542–4516; doi: 10.1038/s41598-023-31586-9
ManasaK, VaniR. Influence of Oxidative Stress on Stored Platelets. Adv Hematol, 2016; 2016(1):4091461; doi: 10.1155/2016/4091461
87.
SixKR, CompernolleV, FeysHB. Platelet biochemistry and morphology after cryopreservation. Int J Mol Sci, 2020; 21(3):935; doi: 10.3390/IJMS21030935
88.
BaghdadiV, RanjbaranR, YariF, et al.Trehalose an additive solution for platelet concentrate to protect platelets from apoptosis and clearance during their storage At 4°C. Cell J, 2022; 24(2):69–75; doi: 10.22074/cellj.2022.7886
89.
PietramaggioriG, KaipainenA, HoD, et al.Trehalose lyophilized platelets for wound healing. Wound Repair Regen, 2007; 15(2):213–220; doi: 10.1111/j.1524-475X.2007.00207.x
90.
RolsmaJL, DarchW, HigginsNC, et al.The tardigrade-derived mitochondrial abundant heat soluble protein improves adipose-derived stem cell survival against representative stressors. Sci Rep, 2024; 14(1):11834; doi: 10.1038/S41598-024-62693-W
91.
Kupiec-WeglinskiJW. Grand challenges in organ transplantation. Front Transplant, 2022; 1:897679; doi: 10.3389/frtra.2022.897679
92.
MauerhoferC, GrumetL, SchemmerP, et al.Combating ischemia-reperfusion injury with micronutrients and natural compounds during solid organ transplantation: Data of clinical trials and lessons of preclinical findings. Int J Mol Sci, 2021; 22(19):10675; doi: 10.3390/IJMS221910675
93.
PiszkiewiczS, GunnKH, WarmuthO, et al.Protecting activity of desiccated enzymes. Protein Sci, 2019; 28(5):941–951; doi: 10.1002/PRO.3604
94.
MencucciR, FavuzzaE, DecandiaG, et al.Hyaluronic acid/trehalose ophthalmic solution in reducing post-cataract surgery dry eye signs and symptoms: A prospective, interventional, randomized, open-label study. J Clin Med, 2021; 10(20):4699; doi: 10.3390/JCM10204699
95.
HatayamaN, YoshidaY, SekiK. A study on the perfusion preservation, resuscitation, and transplantation of a rat heart isolated for 96 hours. Cell Transplant, 2009; 18(5):529–534.
96.
TharasanitT, ThuwanutP. Oocyte cryopreservation in domestic animals and humans: Principles, techniques and updated outcomes. Animals (Basel), 2021; 11(10):2949; doi: 10.3390/ANI11102949
97.
ErogluA, BaileySE, TonerM, et al.Successful cryopreservation of mouse oocytes by using low concentrations of trehalose and dimethylsulfoxide. Biol Reprod, 2009; 80(1):70–78; doi: 10.1095/BIOLREPROD.108.070383
