Skip to main content
SpringerLink
Log in

Dietary intake of microplastics impairs digestive performance, induces hepatic dysfunction, and shortens lifespan in the annual fish Nothobranchius guentheri

Biogerontology Aims and scope Submit manuscript

Cite this article

Abstract

Microplastics (MPs) are ubiquitous in aquatic and terrestrial ecosystem, increasingly becoming a serious concern of human health. Many studies have explored the biological effects of MPs on animal and plant life in recent years. However, information regarding the effects of MPs on aging and lifespan is completely lacking in vertebrate species to date. Here we first confirm the bioavailability of MPs by oral delivery in the annual fish N. guentheri. We then show for the first time that administration of MPs not only shortens the lifespan but also accelerates the development of age-related biomarkers in N. guentheri. We also demonstrate that administration of MPs induces oxidative stress, suppresses antioxidant enzymes, reduces digestive enzymes, and causes hepatic dysfunction. Therefore, we propose that administration of MPs reduces lifespan of N. guentheri via induction of both suppressed antioxidant system and digestive disturbance as well as hepatic damage. Our results also suggest that smaller MPs appear more toxic to digestion, metabolism and growth of animals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Alimba CG, Faggio C (2019) Microplastics in the marine environment: Current trends in environmental pollution and mechanisms of toxicological profile. Environ Toxicol Phar 68:61–74

    Article  CAS  Google Scholar 

  • Ames BN, Shigenaga MK (1992) Oxidants are a major contributor to aging. Ann N Y Acad Sci 663:85–96

    Article  CAS  PubMed  Google Scholar 

  • Andrady AL (2011) Microplastics in the marine environment. Mar Pollut Bull 62:1596–1605

    Article  CAS  PubMed  Google Scholar 

  • Au SY, Bruce TF, Bridges WC, Klaine SJ (2015) Responses of Hyalella azteca to acute and chronic microplastic exposures. Environ Toxicol Chem 34:2564–2572

    Article  CAS  PubMed  Google Scholar 

  • Avio CG, Gorbi S, Milan M et al (2015) Pollutants bioavailability and toxicological risk from microplastics to marine mussels. Environ Pollut 198:211–222

    Article  CAS  PubMed  Google Scholar 

  • Balmer RT (1982) The effect of age on body energy content of the annual cyprinodont fish, Nothobranchius guentheri. Exp Gerontol 17:139–143

    Article  CAS  PubMed  Google Scholar 

  • Banaee M, Sureda A, Zohiery F, Nematdoust HB, Garanzini DS (2014) Alterations in biochemical parameters of the freshwater fish, Alburnus mossulensis, exposed to sub-lethal concentrations of Fenpropathrin. Int J Aquat Biol 2:58–68

    Google Scholar 

  • Brennecke D, Ferreira EC, Costa TMM, Appel D, da Gama BAP, Lenz M (2015) Ingested microplastics (>100 μm) are translocated to organs of the tropical fiddler crab Uca rapax. Mar Pollut Bull 96:491–495

    Article  CAS  PubMed  Google Scholar 

  • Browne MA, Dissanayake A, Galloway TS, Lowe DM, Thompson RC (2008) Ingested microscopic plastic translocates to the circulatory system of the mussel, Mytilus edulis (L). Environ Sci Technol 42:5026–5031

    Article  CAS  PubMed  Google Scholar 

  • Browne MA, Crump P, Niven SJ et al (2011) Accumulation of microplastic on shorelines worldwide: sources and sinks. Environ Sci Technol 45:9175–9179

    Article  CAS  PubMed  Google Scholar 

  • Checa J, Aran JM (2020) Reactive oxygen species: drivers of physiological and pathological processes. J Inflamm Res 13:1057–1073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen W, Chen Z, Shan S, Wu A, Zhao C, Ye X et al (2022) Cyanidin-3-O-glucoside promotes stress tolerance and lifespan extension of Caenorhabditis elegans exposed to polystyrene via DAF-16 pathway. Mech Ageing Dev 207:111723

    Article  CAS  PubMed  Google Scholar 

  • Cole M, Lindeque P, Halsband C, Galloway TS (2011) Microplastics as contaminants in the marine environment: a review. Mar Pollut Bull 62:2588–2597

    Article  CAS  PubMed  Google Scholar 

  • Cooper EL, Zapata A, Garcia Barrutia M, Ramirez JA (1983) Aging changes in lymphopoietic and myelopoietic organs of the annual cyprinodont fish, Nothobranchius guentheri. Exp Gerontol 18:29–38

    Article  CAS  PubMed  Google Scholar 

  • da Costa JP, Santos PSM, Duarte AC, Rocha-Santos T (2016) (Nano) plastics in the environment-sources, fates and effects. Sci Total Environ 566–567:15–26

    Article  PubMed  Google Scholar 

  • Dantas DV, Barletta M, da Costa MF (2012) The seasonal and spatial patterns of ingestion of polyfilament nylon fragments by estuarine drums (Sciaenidae). Environ Sci Pollut R 19:600–606

    Article  Google Scholar 

  • David KA, Barnes FG, Richard C, Thompson MB (2009) Accumulation and fragmentation of plastic debris in global environments. Philos Tran R Soc B 364:1985–1998

    Article  Google Scholar 

  • Ding J, Zhang S, Razanajatovo RM, Zou H, Zhu W (2018) Accumulation, tissue distribution, and biochemical effects of polystyrene microplastics in the freshwater fish red tilapia (Oreochromis niloticus). Environ Pollut 238:1–9

    Article  CAS  PubMed  Google Scholar 

  • Dong Y, Cui P, Li Z, Zhang S (2017) Aging asymmetry: systematic survey of changes in age-related biomarkers in the annual fish Nothobranchius guentheri. Fish Physiol Biochem 43:309–319

    Article  CAS  PubMed  Google Scholar 

  • Eerkes-Medrano D, Thompson RC, Aldridge DC (2015) Microplastics in freshwater systems: a review of the emerging threats, identification of knowledge gaps and prioritisation of research needs. Water Res 75:63–82

    Article  CAS  PubMed  Google Scholar 

  • Foley CJ, Feiner ZS, Malinich TD, Höök TO (2018) A meta-analysis of the effects of exposure to microplastics on fish and aquatic invertebrates. Sci Total Environ 631–632:550–559

    Article  PubMed  Google Scholar 

  • Frydkjær CK, Iversen N, Roslev P (2017) Ingestion and egestion of microplastics by the Cladoceran Daphnia magna: effects of regular and irregular shaped plastic and sorbed phenanthrene. Bull Environ Contam Toxicol 99:655–661

    Article  PubMed  Google Scholar 

  • Giordano M, Croci DO, Rabinovich GA (2013) Galectins in hematological malignancies. Curr Opin Hematol 20:327–335

    Article  CAS  PubMed  Google Scholar 

  • Guo T, Yang Y, Meng F et al (2020) Effects of low salinity on gill and liver glycogen metabolism of great blue-spotted mudskippers (Boleophthalmus pectinirostris). Comp Biochem Phys C 230:108709

    CAS  Google Scholar 

  • Hamed M, Soliman HAM, Osman AGM, Sayed AEH (2020) Antioxidants and molecular damage in Nile Tilapia (Oreochromis niloticus) after exposure to microplastics. Environ Sci Pollut Res Int 27:14581–14588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Horton AA, Walton A, Spurgeon DJ, Lahive E, Svendsen C (2017) Microplastics in freshwater and terrestrial environments: evaluating the current understanding to identify the knowledge gaps and future research priorities. Sci Total Environ 586:127–141

    Article  CAS  PubMed  Google Scholar 

  • Hsu CY, Chiu YC (2009) Ambient temperature influences aging in an annual fish (Nothobranchius rachovii). Aging Cell 8:726–737

    Article  CAS  PubMed  Google Scholar 

  • Hsu CY, Chiu YC, Hsu WL, Chan YP (2008) Age-related markers assayed at different developmental stages of the annual fish Nothobranchius rachovii. J Gerontol A Biol Sci Med Sci 63:1267–1276

    Article  PubMed  Google Scholar 

  • Huang JN, Wen B, Zhu JG et al (2020) Exposure to microplastics impairs digestive performance, stimulates immune response and induces microbiota dysbiosis in the gut of juvenile guppy (Poecilia reticulata). Sci Total Environ 733:138929

    Article  CAS  PubMed  Google Scholar 

  • Iheanacho SC, Odo GE (2020) Dietary exposure to polyvinyl chloride microparticles induced oxidative stress and hepatic damage in Clarias gariepinus (Burchell, 1822). Environ Sci Pollut Res Int 27:21159–21173

    Article  CAS  PubMed  Google Scholar 

  • Imhof HK, Ivleva NP, Schmid J, Niessner R, Laforsch C (2013) Contamination of beach sediments of a subalpine lake with microplastic particles. Curr Biol 23:R867–R868

    Article  CAS  PubMed  Google Scholar 

  • Izvekova GI, Frolova TV, Izvekov EI, Kashinskaya EN, Solovyev MM (2021) Localization of the proteinase inhibitor activity in the fish cestode Eubothrium rugosum. J Fish Dis 44:1951–1958

    Article  CAS  PubMed  Google Scholar 

  • Jabeen K, Su L, Li J et al (2017) Microplastics and mesoplastics in fish from coastal and fresh waters of China. Environ Pollut 221:141–149

    Article  CAS  PubMed  Google Scholar 

  • Jovanović B (2017) Ingestion of microplastics by fish and its potential consequences from a physical perspective. Integr Environ Assess Manag 13:510–515

    Article  PubMed  Google Scholar 

  • Jovanović B, Gökdağ K, Güven O et al (2018) Virgin microplastics are not causing imminent harm to fish after dietary exposure. Mar Pollut Bull 130:123–131

    Article  PubMed  Google Scholar 

  • Khosrovyan A, Kahru A (2020) Evaluation of the hazard of irregularly-shaped co-polyamide microplastics on the freshwater non-biting midge Chironomus riparius through its life cycle. Chemosphere 244:125487

    Article  CAS  PubMed  Google Scholar 

  • Kishi S, Uchiyama J, Baughman AM, Goto T, Lin MC, Tsai SB (2003) The zebrafish as a vertebrate model of functional aging and very gradual senescence. Exp Gerontol 38:777–786

    Article  PubMed  Google Scholar 

  • Liang B, Zhang D, Liu X et al (2022) Sex-specific effects of PET-MPs on Drosophila lifespan. Arch Insect Biochem Physiol 110:e21909

    Article  CAS  PubMed  Google Scholar 

  • Li C, Song L, Zhou Y, Yuan J, Zhang S (2022) Identification of Isthmin1 in the small annual fish, Nothobranchius guentheri, as a novel biomarker of aging and its potential rejuvenation activity. Biogerontology 23:99–114

    Article  CAS  PubMed  Google Scholar 

  • Liu C, Wang X, Feng W et al (2012) Differential express ion of aging biomarkers at different life stages of the annual fish Nothobranchius guentheri. Biogerontology 13:501–510

    Article  CAS  PubMed  Google Scholar 

  • Liu T, Qi H, Ma L et al (2015) Resveratrol attenuates oxidative stress and extends life span in the annual fish Nothobranchius guentheri. Rejuvenation Res 18:225–233

    Article  PubMed  Google Scholar 

  • Liu S, Zheng Z, Ji S, Liu T, Hou Y, Li S, Li G (2018) Resveratrol reduces senescence-associated secretory phenotype by SIRT1/NF-κB pathway in gut of the annual fish Nothobranchius guentheri. Fish Shellfish Immunol 80:473–479

    Article  CAS  PubMed  Google Scholar 

  • Lu Y, Zhang Y, Deng Y et al (2016) Uptake and accumulation of polystyrene microplastics in zebrafish (Danio rerio) and toxic effects in liver. Environ Sci Technol 50:4054–4060

    Article  CAS  PubMed  Google Scholar 

  • Markofsky J (1976) Longitudinal and cross-sectional observations of growth and body composition with age in laboratory populations of the male annual cyprinodont fish, Nothobranchius guentheri. Exp Gerontol 11:171–177

    Article  CAS  PubMed  Google Scholar 

  • Markofsky J, Milstoc M (1979a) Aging changes in the liver of the male annual cyprinodont fish, Nothobranchius guentheri. Exp Gerontol 14:11–20

    Article  CAS  PubMed  Google Scholar 

  • Markofsky J, Milstoc M (1979b) Histopathological observations of the kidney during aging of the male annual fish Nothobranchius guentheri. Exp Gerontol 14:149–155

    Article  CAS  PubMed  Google Scholar 

  • Markofsky J, Perlmutter A (1972) Age at sexual maturity and its relationship to longevity in the male annual cyprinodont fish, Nothobranchius guentheri. Exp Gerontol 7:131–135

    Article  CAS  PubMed  Google Scholar 

  • Markofsky J, Perlmutter A (1973) Growth differences in subgroups of varying longevities in a laboratory population of the male annual cyprinodont fish, Nothobranchius guentheri (Peters). Exp Gerontol 8:65–73

    Article  CAS  PubMed  Google Scholar 

  • Meller K, Pomastowski P, Grzywinski D, Szumski M, Buszewski B (2016) Preparation and evaluation of dual-enzyme microreactor with co-immobilized trypsin and chymotrypsin. J Chromatogr A 1440:45–54

    Article  CAS  PubMed  Google Scholar 

  • Mosiichuk N, Husak V, Storey KB, Lushchak V (2021) Acute exposure to the penconazole-containing fungicide topas induces metabolic stress in goldfish. Chem Res Toxicol 34:2441–2449

    Article  CAS  PubMed  Google Scholar 

  • Okutan H, Savas C, Delibas N (2004) The antioxidant effect of melatonin in lung injury after aortic occlusion-reperfusion. Interact Cardiov Th 3:519–522

    Article  Google Scholar 

  • Phuong NN, Zalouk-Vergnoux A, Poirier L, Kamari A, Châtel A, Mouneyrac C, Lagarde F (2016) Is there any consistency between the microplastics found in the field and those used in laboratory experiments? Environ Pollut 211:111–123

    Article  CAS  PubMed  Google Scholar 

  • Reichwald K, Lauber C, Nanda I et al (2009) High tandem repeat content in the genome of the short-lived annual fish Nothobranchius furzeri: a new vertebrate model for aging research. Genome Biol 10:R16

    Article  PubMed  PubMed Central  Google Scholar 

  • Rochman CM, Hoh E, Kurobe T, Teh SJ (2013) Ingested plastic transfers hazardous chemicals to fish and induces hepatic stress. Sci Rep 3:3263

    Article  PubMed  PubMed Central  Google Scholar 

  • Schwabl P, Köppel S, Königshofer P et al (2019) Detection of various microplastics in human stool: a prospective case series. Ann Intern Med 171:453–457

    Article  PubMed  Google Scholar 

  • Shang X, Lu JW, Feng C et al (2020) Microplastic (1 and 5μm) exposure disturbs lifespan and intestine function in the nematode Caenorhabditis elegans. Sci Total Environ 705:135837

    Article  CAS  PubMed  Google Scholar 

  • Shihabi ZK, Bishop C (1971) Simplified turbidimetric assay for lipase activity. Clin Chem 17:1150–1153

    Article  CAS  PubMed  Google Scholar 

  • Shi L, Tu BP (2015) Acetyl-CoA and the regulation of metabolism: mechanisms and consequences. Curr Opin Cell Biol 33:125–131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sohal RS, Agarwal S, Dubey A, Orr WC (1993) Protein oxidative damage is associated with life expectancy of houseflies. Proc Natl Acad Sci USA 90:7255–7259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song L, Yuan J, Ni S et al (2020) Enhancement of adaptive immune responses of aged mice by dietary intake of β-glucans, with special emphasis on anti-aging activity. Mol Immunol 117:160–167

    Article  CAS  PubMed  Google Scholar 

  • Song L, Li C, Wu F, Zhang S (2022) Dietary intake of diosgenin delays aging of male fish Nothobranchius guentheri through modulation of multiple pathways that play prominent roles in ROS production. Biogerontology 23:201–213

    Article  CAS  PubMed  Google Scholar 

  • Spitz DR, Oberley LW (1989) An assay for superoxide dismutase activity in mammalian tissue homogenates. Anal Biochem 179:8–18

    Article  CAS  PubMed  Google Scholar 

  • Su L, Xue Y, Li L et al (2016) Microplastics in taihu lake, China. Environ Pollut 216:711–719

    Article  CAS  PubMed  Google Scholar 

  • Terzibasi E, Lefrançois C, Domenici P et al (2009) Effects of dietary restriction on mortality and age-related phenotypes in the short-lived fish Nothobranchius furzeri. Aging Cell 8:88–99

    Article  CAS  PubMed  Google Scholar 

  • Torres-Agullo A, Karanasiou A, Moreno T, Lacorte S (2021) Overview on the occurrence of microplastics in air and implications from the use of face masks during the COVID-19 pandemic. Sci Total Environ 800:149555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Triebskorn R, Braunbeck T, Grummt T et al (2019) Relevance of nano- and microplastics for freshwater ecosystems: a critical review. Trends Anal Chem 110:375–392

    Article  CAS  Google Scholar 

  • Valenzano DR, Cellerino A (2006) Resveratrol and the pharmacology of aging: a new vertebrate model to validate an old molecule. Cell Cycle 5:1027–1032

    Article  CAS  PubMed  Google Scholar 

  • Valenzano DR, Terzibasi E, Cattaneo A, Domenici L, Cellerino A (2006) Temperature affects longevity and age-related locomotor and cognitive decay in the short-lived fish Nothobranchius furzeri. Aging Cell 5:275–278

    Article  CAS  PubMed  Google Scholar 

  • Vatner SF, Zhang J, Oydanich M, Berkman T, Naftalovich R, Vatner DE (2020) Healthful aging mediated by inhibition of oxidative stress. Ageing Res Rev 64:101194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Chang Q, Wang Y, Su F, Zhang S (2014) Late-onset temperature reduction can retard the aging process in aged fish via a combined action of an anti-oxidant system and the insulin/insulin-like growth factor 1 signaling pathway. Rejuven Res 17:507–517

    Article  CAS  Google Scholar 

  • Wang X, Du X, Zhou Y et al (2017) Intermittent food restriction initiated late in life prolongs lifespan and retards the onset of age-related markers in the annual fish Nothobranchius guentheri. Biogerontology 18:383–396

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Du X, Zhou Y et al (2018) Time-dependent effects of late-onset dietary intake of salidroside on lifespan and age-related biomarkers of the annual fish Nothobranchius guentheri. Oncotarget 9:14882–14894

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang WF, Gao H, Jin SC, Li RJ, Na GS (2019) The ecotoxicological effects of microplastics on aquatic food web, from primary producer to human: a review. Ecotoxicol Environ Saf 173:110–117

    Article  CAS  PubMed  Google Scholar 

  • Wang W, Ge J, Yu X (2020) Bioavailability and toxicity of microplastics to fish species: a review. Ecotoxicol Environ Saf 189:109913

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Zhou B, Chen H, Yuan R, Wang F (2022) Distribution, biological effects and biofilms of microplastics in freshwater systems: a review. Chemosphere 299:134370

    Article  CAS  PubMed  Google Scholar 

  • Wan Z, Wang CY, Zhou JJ, Shen ML et al (2019) Effects of polystyrene microplastics on the composition of the microbiome and metabolism in larval zebrafish. Chemosphere 217:646–658

    Article  CAS  PubMed  Google Scholar 

  • Wei J, Qi H, Liu K et al (2020) Effects of metformin on life span, cognitive ability, and inflammatory response in a short-lived fish. J Gerontol A Biol Sci Med Sci 75:2042–2050

    Article  CAS  PubMed  Google Scholar 

  • Wong JKH, Lee KK, Tang KHD, Yap PS (2020) Microplastics in the freshwater and terrestrial environments: Prevalence, fates, impacts and sustainable solutions. Sci Total Environ 719:137512

    Article  CAS  PubMed  Google Scholar 

  • World Health Organization (2019) Microplastics in drinking-water. https://baijiahao.baidu.com/s?id=1644923998516554568&wfr=spider&for=pc. Accesed 6 June 2022.

  • Xia X, Sun M, Zhou M, Chang Z, Li L (2019) Polyvinyl chloride microplastics induce growth inhibition and oxidative stress in Cyprinus carpio var. larvae. Sci Total Environ 716:136479

    Article  Google Scholar 

  • Yan LJ (2014) Positive oxidative stress in aging and aging-related disease tolerance. Redox Biol 2:165–169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yong CQY, Valiyaveettil S, Tang BL (2020) Toxicity of microplastics and nanoplastics in mammalian systems. Int J Environ Res Public Health 17:1509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang K, Xiong X, Hu H et al (2017) Occurrence and characteristics of microplastic pollution in xiangxi bay of three gorges reservoir, China. Environ Sci Technol 51:3794–3801

    Article  CAS  PubMed  Google Scholar 

  • Zhou Y, Ni SS, Song LL, Wang X et al (2019) Late-onset administration of GDF11 extends life span and delays development of age-related markers in the annual fish Nothobranchius guentheri. Biogerontology 20:225–239

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all the participants for their valuable contribution to this study.

Funding

This work was supported by the Ministry of Science and Technology (MOST) of China (2018YFD0900505) and the Natural Science Foundation of China (32073000).

Author information

Author notes

  1. Kun Xiao and Lili Song have contributed equally to the work.

Authors and Affiliations

  1. Institute of Evolution & Marine Biodiversity and Department of Marine Biology, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China

    Kun Xiao, Lili Song, Yishuai Li, Congjun Li & Shicui Zhang

  2. Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, 266003, China

    Shicui Zhang

Authors
  1. Kun Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lili Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yishuai Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Congjun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shicui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SZ: Funding acquisition, Conceptualization, Data curation, Writing–review & editing; KX: Resources, Methodology, Investigation, Data curation, Writing–original draft; LS: Methodology, Investigation, Software Writing–original draft; YL: Resources; CL: Resources. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Shicui Zhang.

Ethics declarations

Competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethical approval

This work has received approval for research ethics from Academic Committee Office, Ocean University of China and a proof/certificate of approval is available upon request.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xiao, K., Song, L., Li, Y. et al. Dietary intake of microplastics impairs digestive performance, induces hepatic dysfunction, and shortens lifespan in the annual fish Nothobranchius guentheri. Biogerontology 24, 207–223 (2023). https://doi.org/10.1007/s10522-022-10007-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-022-10007-w

Keywords

search

Navigation