Strategic directions at the intersection of cryobiology and geroscience

Abstract

Cryobiology and geroscience share complementary goals in understanding and mitigating biological damage. Cryopreservation enables the long-term storage of living cells, tissues, and organs, with direct applications in aging-related interventions requiring transplantation, cell therapies, and regenerative approaches. Advances in cryopreservation technologies may expand biobanking of viable specimens across the lifespan, thus facilitating studies of aging phenotypes, biomarker discovery, drug screening, and therapeutic development. Notably, cryoinjury and biological aging share several common molecular features, including oxidative stress, DNA damage, protein misfolding, and mitochondrial dysfunction. These parallels suggest that repurposing geroscience-informed interventions may improve preservation outcomes by enhancing cellular resistance to cryogenic stress and post-thaw recovery. Here, representative opportunities at the interface of cryobiology and geroscience are summarized, emphasizing bidirectional strategies that may advance both fields. This Perspective builds upon discussions from the 2025 Quantitative Approaches and Understudied Questions in the Biology of Aging Workshop (Paris, France).

Keywords

Cryopreservation / transplantation / biobanking / cryoinjury

Acknowledgements

The author utilized ChatGPT (OpenAI) to improve the grammar and clarity of the final draft. The authors take full responsibility for the integrity, originality, and accuracy of the work.

Authors contribution

The author contributed solely to the article.

Conflicts of interest

Rebecca D. Sandlin holds issued and pending patents related to biopreservation technologies. No other competing interests to declare.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This work was supported by the National Science Foundation (Grant No. 2440587).

Copyright

© The Author(s) 2026.

References

[1] Mazur P. Cryobiology: The freezing of biological systems. Science. 1970; 168(3934):939-949.

[2] Bezinover D, Saner F. Organ transplantation in the modern era. BMC Anesthesiol. 2019; 19(1):32.

[3] Rana A, Gruessner A, Agopian VG, Khalpey Z, Riaz IB, Kaplan B, et al. Survival benefit of solid-organ transplant in the United States. JAMA Surg. 2015; 150(3):252.

[4] Lewis JK, Bischof JC, Braslavsky I, Brockbank KGM, Fahy GM, Fuller BJ, et al. The Grand Challenges of Organ Banking: Proceedings from the first global summit on complex tissue cryopreservation. Cryobiology. 2016; 72(2):169-182.

[5] Tessier SN, de Vries RJ, Pendexter CA, Cronin SEJ, Ozer S, Hafiz EOA, et al. Partial freezing of rat livers extends preservation time by 5-fold. Nat Commun. 2022; 13(1):4008.

[6] Giwa S, Lewis JK, Alvarez L, Langer R, Roth AE, Church GM, et al. The promise of organ and tissue preservation to transform medicine. Nat Biotechnol. 2017; 35(6):530-542.

[7] Chen J, Liu X, Hu Y, Chen X, Tan S. Cryopreservation of tissues and organs: Present, bottlenecks, and future. Front Vet Sci. 2023; 10:1201794.

[8] Gangwar L, Han Z, Scheithauer C, Namsrai BE, Kantesaria S, Goldstein R, et al. Physical vitrification and nanowarming at liter-scale CPA volumes: Toward organ cryopreservation. Nat Commun. 2025; 16(1):8511.

[9] Han Z, Rao JS, Gangwar L, Namsrai BE, Pasek-Allen JL, Etheridge ML, et al. Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model. Nat Commun. 2023; 14(1):3407.

[10] de Vries RJ, Tessier SN, Banik PD, Nagpal S, Cronin SEJ, Ozer S, et al. Supercooling extends preservation time of human livers. Nat Biotechnol. 2019; 37(10):1131-1136.

[11] Isiksacan Z, D’Alessandro A, Wolf SM, McKenna DH, Tessier SN, Kucukal E, et al. Assessment of stored red blood cells through lab-on-a-chip technologies for precision transfusion medicine. Proc Natl Acad Sci U S A. 2023; 120(32):e2115616120.

[12] Zhan L, Rao JS, Sethia N, Slama MQ, Han Z, Tobolt D, et al. Pancreatic islet cryopreservation by vitrification achieves high viability, function, recovery and clinical scalability for transplantation. Nat Med. 2022; 28(4):798-808.

[13] Patel KK, Tariveranmoshabad M, Kadu S, Shobaki N, June C. From concept to cure: The evolution of CAR-T cell therapy. Mol Ther. 2025; 33(5):2123-2140.

[14] Garay RP. Recent clinical trials with stem cells to slow or reverse normal aging processes. Front Aging. 2023; 4:1148926.

[15] Meneghel J, Kilbride P, Morris GJ. Cryopreservation as a key element in the successful delivery of cell-based therapies: A review. Front Med. 2020; 7:592242.

[16] Coopman K, Medcalf N. From production to patient: Challenges and approaches for delivering cell therapies. In: StemBook [Internet]. Cambridge: Harvard Stem Cell Institute; 2014.

[17] Cottle C, Porter AP, Lipat A, Turner-Lyles C, Nguyen J, Moll G, et al. Impact of cryopreservation and freeze-thawing on therapeutic properties of mesenchymal stromal/stem cells and other common cellular therapeutics. Curr Stem Cell Rep. 2022; 8(2):72-92.

[18] Ha SJ, Kim BG, Lee YA, Kim YH, Kim BJ, Jung SE, et al. Effect of antioxidants and apoptosis inhibitors on cryopreservation of murine germ cells enriched for spermatogonial stem cells. PLoS One. 2016; 11(8):e0161372.

[19] Hoffman T, Khademhosseini A, Langer R. Chasing the paradigm: Clinical translation of 25 years of tissue engineering. Tissue Eng Part A. 2019; 25(9-10):679-687.

[20] Han F, Wang J, Ding L, Hu Y, Li W, Yuan Z, et al. Tissue engineering and regenerative medicine: Achievements, future, and sustainability in Asia. Front Bioeng Biotechnol. 2020; 8:83.

[21] Gibson ALF, Holmes JH 4th, Shupp JW, Smith D, Joe V, Carson J, et al. A phase 3, open-label, controlled, randomized, multicenter trial evaluating the efficacy and safety of StrataGraft® construct in patients with deep partial-thickness thermal burns. Burns. 2021; 47(5):1024-1037.

[22] Warburton L, Rubinsky B. Cryopreservation of 3D bioprinted scaffolds with temperature-controlled-cryoprinting. Gels. 2023; 9(6):502.

[23] Lou L, Bilbao-Sainz C. Temperature-controlled cryoprinting vegetarian food with modified macro- and microstructures for dysphagia. ACS Food Sci Technol. 2025; 5(8):3219-3228.

[24] Budharaju H, Sundaramurthi D, Sethuraman S. Biofabrication & cryopreservation of tissue engineered constructs for on-demand applications. Biofabrication. 2024; 16(4):042008.

[25] Gallagher CS, Ginsburg GS, Musick A. Biobanking with genetics shapes precision medicine and global health. Nat Rev Genet. 2025; 26(3):191-202.

[26] Paskal W, Paskal AM, Dębski T, Gryziak M, Jaworowski J. Aspects of modern biobank activity-comprehensive review. Pathol Oncol Res. 2018; 24(4):771-785.

[27] De Souza YG, Greenspan JS. Biobanking past, present and future: Responsibilities and benefits. Aids. 2013; 27(3):303-312.

[28] Zhang S, Wang Z, Wang Y, Zhu Y, Zhou Q, Jian X, et al. A metabolomic profile of biological aging in 250, 341 individuals from the UK Biobank. Nat Commun. 2024; 15(1):8081.

[29] Garg M, Karpinski M, Matelska D, Middleton L, Burren OS, Hu F, et al. Disease prediction with multi-omics and biomarkers empowers case-control genetic discoveries in the UK Biobank. Nat Genet. 2024; 56(9):1821-1831.

[30] Li Y, Tang S, Wang H, Zhu H, Lu Y, Zhang Y, et al. A pancreatic cancer organoid biobank links multi-omics signatures to therapeutic response and clinical evaluation of statin combination therapy. Cell Stem Cell. 2025; 32(9):1369-1389.e14.

[31] Xie S, Luo X, Hong F, Wei Y, Hao Y, Xie X, et al. Towards precision aging biology: Single-Cell multi-omics and advanced AI-Driven strategies. Aging Dis. 2025; 17(2):907-926.

[32] Baust JM, Corwin WL, VanBuskirk R, Baust JG. Biobanking: The future of cell preservation strategies. Adv Exp Med Biol. 2015; 864:37-53.

[33] Walters RG, Millwood IY, Lin K, Schmidt Valle D, McDonnell P, Hacker A, et al. Genotyping and population characteristics of the China kadoorie biobank. Cell Genom. 2023; 3(8):100361.

[34] Litton JE. Launch of an infrastructure for health research: BBMRI-ERIC. Biopreserv Biobanking. 2018; 16(3):233-241.

[35] Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, et al. UK biobank: An open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015; 12(3):e1001779.

[36] Bao Y, Bertoia ML, Lenart EB, Stampfer MJ, Willett WC, Speizer FE, et al. Origin, methods, and evolution of the three nurses' health studies. Am J Public Heal. 2016; 106(9):1573-1581.

[37] Denny JC, Rutter JL, Goldstein DB, Philippakis A, Smoller JW, Jenkins G, et al. N Engl J Med. The "All of Us" Research Program. 2019; 381(7):668-676.

[38] Gao D, Critser JK. Mechanisms of cryoinjury in living cells. ILAR J. 2000; 41(4):187-196.

[39] Martin G, Sabido O, Durand P, Levy R. Cryopreservation induces an apoptosis-like mechanism in bull sperm. Biol Reprod. 2004; 71(1):28-37.

[40] Gualtieri R, Kalthur G, Barbato V, di Nardo M, Adiga SK, Talevi R. Mitochondrial dysfunction and oxidative stress caused by cryopreservation in reproductive cells. Antioxidants. 2021; 10(3):337.

[41] López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013; 153(6):1194-1217.

[42] López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2023; 186(2):243-278.

[43] Murray KA, Gibson MI. Chemical approaches to cryopreservation. Nat Rev Chem. 2022; 6(8):579-593.

[44] Varo-Ghiuru F, Miclea I, Hettig A, Ladoşi I, Miclea V, Egerszegi I, et al. Lutein, Trolox, ascorbic acid and combination of Trolox with ascorbic acid can improve boar semen quality during cryopreservation. Cryo Letters. 2015; 36(1):1-7.

[45] Liu X, Xu Y, Liu F, Pan Y, Miao L, Zhu Q, et al. The feasibility of antioxidants avoiding oxidative damages from reactive oxygen species in cryopreservation. Front Chem. 2021; 9:648684.

[46] Len JS, Koh WSD, Tan SX. The roles of reactive oxygen species and antioxidants in cryopreservation. Biosci Rep. 2019; 39(8):BSR20191601.

[47] Yoshida T, Prudent M, D’Alessandro A. Red blood cell storage lesion: Causes and potential clinical consequences. Blood Transfus. 2019; 17(1):27-52.

[48] Yang J, Guo S, Pan B, Qazi IH, Qin J, Zang S, et al. Melatonin promotes in vitro maturation of vitrified-warmed mouse GV oocytes potentially by modulating MAD2 protein expression of SAC component through MTRs. Cryobiology. 2021; 102:82-91.

[49] Comizzoli P, Wildt DE, Pukazhenthi BS. In vitro compaction of germinal vesicle chromatin is beneficial to survival of vitrified cat oocytes. Reprod Domest Anim. 2009; 44(s2):269-274.

[50] Ruiz-Conca M, Vendrell M, Sabés-Alsina M, Mogas T, Lopez-Bejar M. Coenzyme Q₁₀ supplementation during in vitro maturation of bovine oocytes (Bos Taurus) helps to preserve oocyte integrity after vitrification. Reprod Domest Anim. 2017; 52(Suppl 4):52-54.

[51] Davoodian N, Kadivar A, Ahmadi E, Nazari H, Mehrban H. Quercetin effect on the efficiency of ovine oocyte vitrification at GV stage. Theriogenology. 2021; 174:53-59.

[52] López M, Bollag RJ, Yu JC, Isales CM, Eroglu A. Chemically defined and xeno-free cryopreservation of human adipose-derived stem cells. PLoS One. 2016; 11(3):e0152161.

[53] Sandlin RD, Wong KHK, Boneschansker L, Carey TR, Miller KL, Rose G, et al. Preservative solution that stabilizes erythrocyte morphology and leukocyte viability under ambient conditions. Sci Rep. 2017; 7:5658.

[54] Antosik A, Czubak K, Cichon N, Nowak P, Zbikowska H. Vitamin E analogue protects red blood cells against storage-induced oxidative damage. Transfus Med Hemother. 2018; 45(5):347-354.

[55] Cao B, Qin J, Pan B, Qazi IH, Ye J, Fang Y, et al. Oxidative stress and oocyte cryopreservation: Recent advances in mitigation strategies involving antioxidants. Cells. 2022; 11(22):3573.

[56] Taylor K, Roberts P, Sanders K, Burton P. Effect of antioxidant supplementation of cryopreservation medium on post-thaw integrity of human spermatozoa. Reprod Biomed Online. 2009; 18(2):184-189.

[57] Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature. 2000; 408(6809):239-247.

[58] de Gaetano A, Gibellini L, Zanini G, Nasi M, Cossarizza A, Pinti M. Mitophagy and oxidative stress: The role of aging. Antioxidants. 2021; 10(5):794.

[59] Omori K, Valiente L, Orr C, Rawson J, Ferreri K, Todorov I, et al. Improvement of human islet cryopreservation by a p 38 MAPK inhibitor. Am J Transplant. 2007; 7(5):1224-1232.

[60] He D, Wu H, Xiang J, Ruan X, Peng P, Ruan Y, et al. Gut stem cell aging is driven by mTORC1 via a p38 MAPK-p53 pathway. Nat Commun. 2020; 11:37.

[61] Luo D, Qi X, Xu X, Yang L, Yu C, Guan Q. Involvement of p 38 MAPK in Leydig cell aging and age-related decline in testosterone. Front Endocrinol. 2023; 14:1088249.

[62] Muraleva NA, Kolosova NG. P38 MAPK signaling in the retina: Effects of aging and age-related macular degeneration. Int J Mol Sci. 2023; 24(14):11586.

[63] Venkatasubramanian RT, Grassl ED, Barocas VH, Lafontaine D, Bischof JC. Effects of freezing and cryopreservation on the mechanical properties of arteries. Ann Biomed Eng. 2006; 34(5):823-832.

[64] Eisenberg DP, Bischof JC, Rabin Y. Thermomechanical stress in cryopreservation via vitrification with nanoparticle heating as a stress-moderating effect. J Biomech Eng. 2016; 138(1):011010.

[65] Phillip JM, Aifuwa I, Walston J, Wirtz D. The mechanobiology of aging. Annu Rev Biomed Eng. 2015; 17:113-141.

[66] Zhang H, Davies KJA, Forman HJ. Oxidative stress response and Nrf 2 signaling in aging. Free Radic Biol Med. 2015; 88:314-336.

[67] Mayer C, Riera-Ponsati L, Kauppinen S, Klitgaard H, Erler JT, Hansen SN. Targeting the NRF 2 pathway for disease modification in neurodegenerative diseases: Mechanisms and therapeutic implications. Front Pharmacol. 2024; 15:1437939.

[68] Labbadia J, Morimoto RI. The biology of proteostasis in aging and disease. Annu Rev Biochem. 2015; 84:435-464.

[69] Bonkowski MS, Sinclair DA. Slowing ageing by design: The rise of NAD+ and sirtuin-activating compounds. Nat Rev Mol Cell Biol. 2016; 17(11):679-690.

[70] Xu X, Pang Y, Fan X. Mitochondria in oxidative stress, inflammation and aging: From mechanisms to therapeutic advances. Sig Transduct Target Ther. 2025; 10(1):190.

[71] Wolf SM, Crock BN, Van Ness B, Lawrenz F, Kahn JP, Beskow LM, et al. Managing incidental findings and research results in genomic research involving biobanks and archived data sets. Genet Med. 2012; 14(4):361-384.

[72] McMahon AM, Kolawole OI. Biobank donation in search of public benefits and the potential impact of intellectual property rights over access to health-technologies developed: A focus on the bioethical implications. Med Law Rev. 2024; 32(2):205-228.

[73] Evers K, Forsberg J, Hansson M. Commercialization of biobanks. Biopreserv Biobanking. 2012; 10(1):45-47.

[74] Capron AM, Pruett TL, Childress JF. The big chill: Opportunities for, and challenges to, advanced biopreservation of organs for transplantation. J Law Med Ethics. 2024; 52(3):595-610.

[75] Childress JF, Brister E, Thompson PB, Wolf SM, Callier SL, Capron AM, et al. Ethical issues in emerging technologies to extend the viability of biological materials across time and space. J Law Med Ethics. 2024; 52(3):570-584.