Calibrating a Comprehensive Immune Age Metric to Analyze the Cross Sectional Age-Related Decline in Cardiorespiratory Fitness

Peter Bröde, Maren Claus, Patrick D Gajewski, Stephan Getzmann, Klaus Golka, Jan G Hengstler, Edmund Wascher, Carsten Watzl, Peter Bröde, Maren Claus, Patrick D Gajewski, Stephan Getzmann, Klaus Golka, Jan G Hengstler, Edmund Wascher, Carsten Watzl

Abstract

Cardiorespiratory fitness (CRF) is essential for sustained work ability in good health, but declines with aging, as does the functionality of the immune system, the latter process commonly referred to as immunosenescence. This study aimed to compare the capacity of immunosenescence biomarkers with chronological age for predicting low CRF in a cross-sectional sample recruited from the regional working population. CRF was determined by submaximal bicycle ergometer testing in a cross-sectional sample of 597 volunteers aged 20-70 years from the 'Dortmund Vital Study' (DVS, ClinicalTrials.gov Identifier: NCT05155397). Low CRF was scored if the ergometer test was not completed due to medical reasons or if the power output projected to a heart rate of 130 bpm divided by body mass was below sex-specific reference values of 1.25 W/kg for females and 1.5 W/kg for males, respectively. In addition to established biomarkers of immunosenescence, we calibrated a comprehensive metric of immune age to our data and compared its predictive capacity for low CRF to chronological age, while adjusting our analysis for the influence of sex, obesity, and the level of regular physical activity, by applying univariate and multiple logistic regression. While obesity, low physical activity, chronological and immune age were all associated with increased probability for low CRF in univariate analyses, multiple logistic regression revealed that obesity and physical activity together with immune age, but not chronological age, were statistically significant predictors of low CRF outcome. Sex was non-significant due to the applied sex-specific reference values. These results demonstrate that biological age assessed by our immunological metric can outperform chronological age as a predictor for CRF and indicate a potential role for immunosenescence in explaining the inter-individual variability of the age-related decline in cardiorespiratory fitness.

Keywords: aging; immunosenescence; obesity; physical activity; physical fitness; sex.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Calibration of the IMM-AGE metric [35] to cell-frequency data from the Dortmund Vital Study DVS [23]. (A) Box plots of the age distributions in the IMM-AGE sample and the DVS. (B) Compatibility between IMM-AGE and DVS for five biomarkers of immune age (NK- to T-cell ratio, CD4:CD8 ratio, memory-to-naive ratios for CD8 and CD4 T-cells, CD28- CD8 cells) in relation to chronological age assessed by linear regression and Pearson correlation coefficients (R). The analyses used the logarithms of ratios and the logits of percentages, respectively. (C) Goodness-of-fit in comparison to dashed line of identity assessed by Pearson correlation coefficient and root-mean-squared error (RMSE) of the approximation to the IMM-AGE metric in the original data [35] calculated by principal component regression (IMMAX) with the five biomarkers from (B) as predictors. (D) Age-depending linear regression lines for the IMM-AGE metric and its approximation (IMMAX) in the original data from (C) compared to the approximations calculated for the DVS data (IMMAX.DVS). (E) Linear regression and correlation with age of the approximated IMM-AGE metric in the DVS (IMMAX.DVS) for females and males.
Figure 2
Figure 2
Bivariate associations of low cardiorespiratory fitness (CRF) with (A) categorical and (B) continuous predictors for the subsample of 547 complete observations from the DVS with 199 low CRF events.
Figure 3
Figure 3
Multiple logistic regression results comparing chronological age with different immune age metrics as predictors of low CRF by standardized odds ratios with 95%-CI (left panels, with vertical dashed reference lines indicating null effect) and by Akaike’s information criterion AIC with lower values indicating improved model fit (right panels), respectively. (A) Results using different immune age metrics as predictors in separate models in addition to chronological age, adjusting the analyses for sex, obesity, and physical activity. (B) Results using either chronological age or different immune age metrics as predictor in separate models, adjusting for obesity and physical activity, but excluding sex as covariate.

References

    1. Myers J., McAuley P., Lavie C.J., Despres J.-P., Arena R., Kokkinos P. Physical Activity and Cardiorespiratory Fitness as Major Markers of Cardiovascular Risk: Their Independent and Interwoven Importance to Health Status. Prog. Cardiovasc. Dis. 2015;57:306–314. doi: 10.1016/j.pcad.2014.09.011.
    1. Al-Mallah M.H., Sakr S., Al-Qunaibet A. Cardiorespiratory Fitness and Cardiovascular Disease Prevention: An Update. Curr. Atheroscler. Rep. 2018;20:1. doi: 10.1007/s11883-018-0711-4.
    1. Blair S.N., Kohl H.W., III, Paffenbarger R.S., Jr., Clark D.G., Cooper K.H., Gibbons L.W. Physical Fitness and All-Cause Mortality: A Prospective Study of Healthy Men and Women. JAMA. 1989;262:2395–2401. doi: 10.1001/jama.1989.03430170057028.
    1. Imboden M.T., Harber M.P., Whaley M.H., Finch W.H., Bishop D.L., Kaminsky L.A. Cardiorespiratory Fitness and Mortality in Healthy Men and Women. J. Am. Coll. Cardiol. 2018;72:2283–2292. doi: 10.1016/j.jacc.2018.08.2166.
    1. Burdorf A., Robroek S. Promoting work ability through exercise programmes. Lancet Public Health. 2019;4:e316–e317. doi: 10.1016/S2468-2667(19)30101-X.
    1. Kenny G.P., Groeller H., McGinn R., Flouris A.D. Age, human performance, and physical employment standards. Appl. Physiol. Nutr. Metab. 2016;41:S92–S107. doi: 10.1139/apnm-2015-0483.
    1. Kenny G.P., Yardley J.E., Martineau L., Jay O. Physical work capacity in older adults: Implications for the aging worker. Am. J. Ind. Med. 2008;51:610–625. doi: 10.1002/ajim.20600.
    1. Smolander J., Blair S.N., Kohl H.W.I. Work Ability, Physical Activity, and Cardiorespiratory Fitness: 2-year Results From Project Active. J. Occup. Environ. Med. 2000;42:906–910. doi: 10.1097/00043764-200009000-00012.
    1. Tengland P.A. The concept of work ability. J. Occup. Rehabil. 2011;21:275–285. doi: 10.1007/s10926-010-9269-x.
    1. Ezzatvar Y., Calatayud J., Andersen L.L., Ramos Vieira E., López-Bueno R., Casaña J. Muscular Fitness and Work Ability among Physical Therapists. Int. J. Environ. Res. Public Health. 2021;18:1722. doi: 10.3390/ijerph18041722.
    1. Mänttäri S., Oksa J., Lusa S., Korkiakangas E., Punakallio A., Oksanen T., Laitinen J. Interventions to promote work ability by increasing physical activity among workers with physically strenuous jobs: A scoping review. Scand. J. Public Health. 2021;49:206–218. doi: 10.1177/1403494820917532.
    1. Grabara M., Nawrocka A., Powerska-Didkowska A. The relationship between physical activity and work ability—A cross-sectional study of teachers. Int. J. Occup. Med. Environ. Health. 2018;31:1–9. doi: 10.13075/ijomeh.1896.01043.
    1. Duggal N.A., Niemiro G., Harridge S.D.R., Simpson R.J., Lord J.M. Can physical activity ameliorate immunosenescence and thereby reduce age-related multi-morbidity? Nat. Rev. Immunol. 2019;19:563–572. doi: 10.1038/s41577-019-0177-9.
    1. Spielmann G., Bigley A.B., LaVoy E.C., Simpson R.J. Aging Immunity and the Impact of Physical Exercise. In: Massoud A., Rezaei N., editors. Immunology of Aging. Springer; Berlin/Heidelberg, Germany: 2014. pp. 369–397.
    1. Spielmann G., McFarlin B.K., O’Connor D.P., Smith P.J.W., Pircher H., Simpson R.J. Aerobic fitness is associated with lower proportions of senescent blood T-cells in man. Brain Behav. Immun. 2011;25:1521–1529. doi: 10.1016/j.bbi.2011.07.226.
    1. Smart T.F.F., Doleman B., Hatt J., Paul M., Toft S., Lund J.N., Phillips B.E. The role of resistance exercise training for improving cardiorespiratory fitness in healthy older adults: A systematic review and meta-analysis. Age Ageing. 2022;51:afac143. doi: 10.1093/ageing/afac143.
    1. Fulop T., Larbi A., Dupuis G., Le Page A., Frost E.H., Cohen A.A., Witkowski J.M., Franceschi C. Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes? Front. Immunol. 2018;8:1960. doi: 10.3389/fimmu.2017.01960.
    1. Nieman D.C., Wentz L.M. The compelling link between physical activity and the body’s defense system. J. Sport Health Sci. 2019;8:201–217. doi: 10.1016/j.jshs.2018.09.009.
    1. Rosengren A. Obesity and cardiovascular health: The size of the problem. Eur. Heart J. 2021;42:3404–3406. doi: 10.1093/eurheartj/ehab518.
    1. Kaminsky L.A., Arena R., Myers J., Peterman J.E., Bonikowske A.R., Harber M.P., Medina Inojosa J.R., Lavie C.J., Squires R.W. Updated Reference Standards for Cardiorespiratory Fitness Measured with Cardiopulmonary Exercise Testing: Data from the Fitness Registry and the Importance of Exercise National Database (FRIEND) Mayo Clin. Proc. 2022;97:285–293. doi: 10.1016/j.mayocp.2021.08.020.
    1. Zeiher J., Manz K., Kuntz B., Perumal N., Keil T., Mensink G.B.M., Finger J.D. Individual and interpersonal correlates of cardiorespiratory fitness in adults—Findings from the German Health Interview and Examination Survey. Sci. Rep. 2020;10:445. doi: 10.1038/s41598-019-56698-z.
    1. Matsuo T., So R., Takahashi M. Workers’ physical activity data contribute to estimating maximal oxygen consumption: A questionnaire study to concurrently assess workers’ sedentary behavior and cardiorespiratory fitness. BMC Public Health. 2020;20:22. doi: 10.1186/s12889-019-8067-4.
    1. Gajewski P.D., Getzmann S., Bröde P., Burke M., Cadenas C., Capellino S., Claus M., Genç E., Golka K., Hengstler J.G., et al. Impact of Biological and Lifestyle Factors on Cognitive Aging and Work Ability in the Dortmund Vital Study: Protocol of an Interdisciplinary, Cross-sectional, and Longitudinal Study. JMIR Res. Protoc. 2022;11:e32352. doi: 10.2196/32352.
    1. Gajewski P., Rieker J.A., Athanassiou G., Bröde P., Claus M., Golka K., Hengstler J., Kleinsorge T., Nitsche M., Reinders J., et al. A Systematic Analysis Of Biological And Environmental Factors Contributing To Work Ability Across The Working Lifespan: A Cross-Sectional Study (Preprint) JMIR Prepr. 2022 doi: 10.2196/preprints.40818.
    1. Wood T.R., Jóhannsson G.F. Metabolic health and lifestyle medicine should be a cornerstone of future pandemic preparedness. Lifestyle Med. 2020;1:e2. doi: 10.1002/lim2.2.
    1. Rutledge J., Oh H., Wyss-Coray T. Measuring biological age using omics data. Nat. Rev. Genet. 2022 doi: 10.1038/s41576-022-00511-7.
    1. Ahadi S., Zhou W., Schüssler-Fiorenza Rose S.M., Sailani M.R., Contrepois K., Avina M., Ashland M., Brunet A., Snyder M. Personal aging markers and ageotypes revealed by deep longitudinal profiling. Nat. Med. 2020;26:83–90. doi: 10.1038/s41591-019-0719-5.
    1. Levine M.E. Modeling the Rate of Senescence: Can Estimated Biological Age Predict Mortality More Accurately Than Chronological Age? J. Gerontol. Ser. A. 2012;68:667–674. doi: 10.1093/gerona/gls233.
    1. Levine M.E., Lu A.T., Quach A., Chen B.H., Assimes T.L., Bandinelli S., Hou L., Baccarelli A.A., Stewart J.D., Li Y., et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging. 2018;10:573–591. doi: 10.18632/aging.101414.
    1. Goudsmit J., van den Biggelaar A.H.J., Koudstaal W., Hofman A., Koff W.C., Schenkelberg T., Alter G., Mina M.J., Wu J.W. Immune age and biological age as determinants of vaccine responsiveness among elderly populations: The Human Immunomics Initiative research program. Eur. J. Epidemiol. 2021;36:753–762. doi: 10.1007/s10654-021-00767-z.
    1. Higgins-Chen A.T., Thrush K.L., Levine M.E. Aging biomarkers and the brain. Semin. Cell Dev. Biol. 2021;116:180–193. doi: 10.1016/j.semcdb.2021.01.003.
    1. Pawelec G. Age and immunity: What is “immunosenescence”? Exp. Gerontol. 2018;105:4–9. doi: 10.1016/j.exger.2017.10.024.
    1. Aw D., Silva A.B., Palmer D.B. Immunosenescence: Emerging challenges for an ageing population. Immunology. 2007;120:435–446. doi: 10.1111/j.1365-2567.2007.02555.x.
    1. Xu W., Wong G., Hwang Y.Y., Larbi A. The untwining of immunosenescence and aging. Semin. Immunopathol. 2020;42:559–572. doi: 10.1007/s00281-020-00824-x.
    1. Alpert A., Pickman Y., Leipold M., Rosenberg-Hasson Y., Ji X., Gaujoux R., Rabani H., Starosvetsky E., Kveler K., Schaffert S., et al. A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring. Nat. Med. 2019;25:487–495. doi: 10.1038/s41591-019-0381-y.
    1. Brzezińska A., Magalska A., Szybińska A., Sikora E. Proliferation and apoptosis of human CD8+CD28+ and CD8+CD28− lymphocytes during aging. Exp. Gerontol. 2004;39:539–544. doi: 10.1016/j.exger.2003.09.026.
    1. Huff W.X., Kwon J.H., Henriquez M., Fetcko K., Dey M. The Evolving Role of CD8+CD28− Immunosenescent T Cells in Cancer Immunology. Int. J. Mol. Sci. 2019;20:2810. doi: 10.3390/ijms20112810.
    1. Goronzy J.J., Fang F., Cavanagh M.M., Qi Q., Weyand C.M. Naive T Cell Maintenance and Function in Human Aging. J. Immunol. 2015;194:4073–4080. doi: 10.4049/jimmunol.1500046.
    1. Weyand C.M., Goronzy J.J. Aging of the Immune System. Mechanisms and Therapeutic Targets. Ann. Am. Thorac. Soc. 2016;13:S422–S428. doi: 10.1513/AnnalsATS.201602-095AW.
    1. Fagnoni F.F., Vescovini R., Passeri G., Bologna G., Pedrazzoni M., Lavagetto G., Casti A., Franceschi C., Passeri M., Sansoni P. Shortage of circulating naive CD8+ T cells provides new insights on immunodeficiency in aging. Blood. 2000;95:2860–2868. doi: 10.1182/blood.V95.9.2860.009k35_2860_2868.
    1. Garrido-Rodríguez V., Herrero-Fernández I., Castro M.J., Castillo A., Rosado-Sánchez I., Galvá M.I., Ramos R., Olivas-Martínez I., Bulnes-Ramos Á., Cañizares J., et al. Immunological features beyond CD4/CD8 ratio values in older individuals. Aging. 2021;13:13443–13459. doi: 10.18632/aging.203109.
    1. Wikby A., Månsson I.A., Johansson B., Strindhall J., Nilsson S.E. The immune risk profile is associated with age and gender: Findings from three Swedish population studies of individuals 20–100 years of age. Biogerontology. 2008;9:299–308. doi: 10.1007/s10522-008-9138-6.
    1. Hirokawa K., Utsuyama M., Hayashi Y., Kitagawa M., Makinodan T., Fulop T. Slower immune system aging in women versus men in the Japanese population. Immun. Ageing. 2013;10:19. doi: 10.1186/1742-4933-10-19.
    1. Ramasubramanian R., Meier H.C.S., Vivek S., Klopack E., Crimmins E.M., Faul J., Nikolich-Žugich J., Thyagarajan B. Evaluation of T-cell aging-related immune phenotypes in the context of biological aging and multimorbidity in the Health and Retirement Study. Immun. Ageing. 2022;19:33. doi: 10.1186/s12979-022-00290-z.
    1. Rizzo L.B., Swardfager W., Maurya P.K., Graiff M.Z., Pedrini M., Asevedo E., Cassinelli A.C., Bauer M.E., Cordeiro Q., Scott J., et al. An immunological age index in bipolar disorder: A confirmatory factor analysis of putative immunosenescence markers and associations with clinical characteristics. Int. J. Methods Psychiatr. Res. 2018;27:e1614. doi: 10.1002/mpr.1614.
    1. Sayed N., Huang Y., Nguyen K., Krejciova-Rajaniemi Z., Grawe A.P., Gao T., Tibshirani R., Hastie T., Alpert A., Cui L., et al. An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging. Nat. Aging. 2021;1:598–615. doi: 10.1038/s43587-021-00082-y.
    1. Frasca D., Diaz A., Romero M., Garcia D., Blomberg B.B. B Cell Immunosenescence. Annu. Rev. Cell Dev. Biol. 2020;36:551–574. doi: 10.1146/annurev-cellbio-011620-034148.
    1. Furman D., Campisi J., Verdin E., Carrera-Bastos P., Targ S., Franceschi C., Ferrucci L., Gilroy D.W., Fasano A., Miller G.W., et al. Chronic inflammation in the etiology of disease across the life span. Nat. Med. 2019;25:1822–1832. doi: 10.1038/s41591-019-0675-0.
    1. Guerville F., De Souto Barreto P., Ader I., Andrieu S., Casteilla L., Dray C., Fazilleau N., Guyonnet S., Langin D., Liblau R., et al. Revisiting the Hallmarks of Aging to Identify Markers of Biological Age. J. Prev. Alzheimer’s Dis. 2020;7:56–64. doi: 10.14283/jpad.2019.50.
    1. Henrickson S.E. Is your immune system over the hill? Sci. Immunol. 2019;4:eaax8198. doi: 10.1126/sciimmunol.aax8198.
    1. Koff W.C., Williams M.A. Covid-19 and Immunity in Aging Populations—A New Research Agenda. N. Engl. J. Med. 2020;383:804–805. doi: 10.1056/NEJMp2006761.
    1. Pawelec G. The human immunosenescence phenotype: Does it exist? Semin. Immunopathol. 2020;42:537–544. doi: 10.1007/s00281-020-00810-3.
    1. Yan Z., Maecker H.T., Brodin P., Nygaard U.C., Lyu S.C., Davis M.M., Nadeau K.C., Andorf S. Aging and CMV discordance are associated with increased immune diversity between monozygotic twins. Immun. Ageing. 2021;18:5. doi: 10.1186/s12979-021-00216-1.
    1. Barletta W.A. The Influence of SARS-CoV-2 Variants on National Case-Fatality Rates: Correlation and Validation Study. JMIRx Med. 2022;3:e32935. doi: 10.2196/32935.
    1. WHO . WHO Technical Report Series. World Health Organization; Geneva, Switzerland: 1995. Physical status: The use and interpretation of anthropometry. Report of a WHO Expert Committee.
    1. Höltke V., Jakob E. Lüdenscheider Aktivitätsfragebogen zum Risikofaktor Bewegungsmangel [Lüdenscheid Physical Activity Questionnaire Concerning the Risk Factor Inactivity] [(accessed on 14 July 2022)]. Available online: .
    1. Farnad L., Ghasemian-Shirvan E., Mosayebi-Samani M., Kuo M.-F., Nitsche M.A. Exploring and optimizing the neuroplastic effects of anodal transcranial direct current stimulation over the primary motor cortex of older humans. Brain Stimul. 2021;14:622–634. doi: 10.1016/j.brs.2021.03.013.
    1. Gajewski P.D., Falkenstein M. Lifelong physical activity and executive functions in older age assessed by memory based task switching. Neuropsychologia. 2015;73:195–207. doi: 10.1016/j.neuropsychologia.2015.04.031.
    1. Getzmann S., Falkenstein M., Gajewski P.D. Long-Term Cardiovascular Fitness Is Associated with Auditory Attentional Control in Old Adults: Neuro-Behavioral Evidence. PLoS ONE. 2013;8:e74539. doi: 10.1371/journal.pone.0074539.
    1. Finger J.D., Gößwald A., Härtel S., Müters S., Krug S., Hölling H., Kuhnert R., Bös K. Messung der kardiorespiratorischen Fitness in der Studie zur Gesundheit Erwachsener in Deutschland (DEGS1) [Measurement of cardiorespiratory fitness in the German Health Interview and Examination Survey for Adults (DEGS1)] Bundesgesundheitsblatt-Gesundh. Gesundh. 2013;56:885–893. doi: 10.1007/s00103-013-1694-5.
    1. Andersen K.L., Shephard R.J., Denolin H., Varnauskas E., Masironi R., World Health Organization Fundamentals of exercise testing. [(accessed on 20 September 2022)]. Available online: .
    1. Fletcher G.F., Ades P.A., Kligfield P., Arena R., Balady G.J., Bittner V.A., Coke L.A., Fleg J.L., Forman D.E., Gerber T.C., et al. Exercise Standards for Testing and Training. Circulation. 2013;128:873–934. doi: 10.1161/CIR.0b013e31829b5b44.
    1. Platen P. Biologische Grundlagen: Beurteilung der körperlichen Leistungsfähigkeit. In: Rost R., editor. Lehrbuch der Sportmedizin. Deutscher Ärzteverlag; Köln, Germany: 2001. pp. 48–66.
    1. Claus M., Dychus N., Ebel M., Damaschke J., Maydych V., Wolf O.T., Kleinsorge T., Watzl C. Measuring the immune system: A comprehensive approach for the analysis of immune functions in humans. Arch. Toxicol. 2016;90:2481–2495. doi: 10.1007/s00204-016-1809-5.
    1. van den Boogaart K.G., Tolosana-Delgado R. Analyzing Compositional Data with R. Springer; Berlin/Heidelberg, Germany: 2013. p. 255.
    1. Liland K.H., Mevik B.-H., Wehrens R. pls: Partial Least Squares and Principal Component Regression. R Foundation for Statistical Computing; Vienna, Austria: 2022. R Package Version 2.8-1.
    1. R Core Team . R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing; Vienna, Austria: 2022.
    1. Smithson M., Verkuilen J. A better lemon squeezer? Maximum-likelihood regression with beta-distributed dependent variables. Psychol. Methods. 2006;11:54–71. doi: 10.1037/1082-989X.11.1.54.
    1. Venables W.N., Ripley B.D. Modern Applied Statistics with S. Springer; New York, NY, USA: 2002. Generalized Linear Models; pp. 183–210.
    1. Burnham K., Anderson D., Huyvaert K. AIC model selection and multimodel inference in behavioral ecology: Some background, observations, and comparisons. Behav. Ecol. Sociobiol. 2011;65:23–35. doi: 10.1007/s00265-010-1029-6.
    1. Finger J.D., Banzer W., Baumeister S.E., Brandes M., Bös K., Gabrys L., Gößwald A., Härtel S., Kluttig A., Kuhnert R., et al. Referenzwerte für die kardiorespiratorische Fitness der allgemeinen Bevölkerung: Die Studie zur Gesundheit Erwachsener in Deutschland (DEGS1) 2008–2011 [Reference Values for Cardiorespiratory Fitness of the General Population: The German National Health Interview and Examination Survey for Adults (DEGS1) 2008–2011] Gesundheitswesen. 2021;83:114–121. doi: 10.1055/a-1026-6220.
    1. Noonan V., Dean E. Submaximal Exercise Testing: Clinical Application and Interpretation. Phys. Ther. 2000;80:782–807. doi: 10.1093/ptj/80.8.782.
    1. Björkman F., Ekblom Ö., Ekblom-Bak E., Bohman T. The ability of a submaximal cycle ergometer test to detect longitudinal changes in VO2max. BMC Sport. Sci. Med. Rehabil. 2021;13:156. doi: 10.1186/s13102-021-00387-w.
    1. Hu B., Jadhav R.R., Gustafson C.E., Le Saux S., Ye Z., Li X., Tian L., Weyand C.M., Goronzy J.J. Distinct Age-Related Epigenetic Signatures in CD4 and CD8 T Cells. Front. Immunol. 2020;11:585168. doi: 10.3389/fimmu.2020.585168.
    1. Pawelec G. Hallmarks of human “immunosenescence”: Adaptation or dysregulation? Immun. Ageing. 2012;9:15. doi: 10.1186/1742-4933-9-15.
    1. Schenk A., Esser T., Belen S., Gunasekara N., Joisten N., Winker M.T., Weike L., Bloch W., Heidenreich A., Herden J., et al. Distinct distribution patterns of exercise-induced natural killer cell mobilisation into the circulation and tumor tissue of patients with prostate cancer. Am. J. Physiol. Cell Physiol. 2022;323:C879–C884. doi: 10.1152/ajpcell.00243.2022.

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