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Frailty is associated with elevated CRP trajectories and higher numbers of neutrophils and monocytes
Open accessAbstract
BACKGROUND: With aging, the human immune system undergoes several changes. The clinical relevance of these changes, however, is relatively unknown. We investigated immunological aspects of human aging in relation to frailty in the Doetinchem Cohort Study (DCS). METHODS: We calculated a frailty index score based on 36 health parameters for each individual in the DCS with data obtained in the period 2008-2016. The frailty index was used to define three health groups ('healthy', 'intermediate', and 'frail'), stratified by age and sex. In a subcohort (n = 289, 60-85 years, selected by balanced random sampling per frailty group), we collected blood samples between October 2016 and March 2017 to determine absolute numbers of leukocyte subsets. In addition, cytomegalovirus serostatus was assessed. C-reactive protein (CRP) levels were longitudinally assessed in four consecutive plasma samples per individual. These samples had been previously collected (1993-2013) as part of the DCS at regular time intervals and spanning a period of >15 years. RESULTS: We observed higher numbers of myeloid derived neutrophils and monocytes in the frail group compared to the healthy group in both men and women, and, retrospectively, consistently higher CRP concentrations over a period of >15 years. An increase in CRP concentration with age was found in women, but not in men. Frailty was not associated with cytomegalovirus serostatus or with changes in lymphoid derived T-, B-, or NK-cell numbers. CONCLUSION: Frail elderly, compared to their age- and sex-matched peers, endure a chronic and stable low-grade inflammation, which is associated with a myeloid cell lineage expansion. These findings could help to monitor clinically significant immunological decline in the elderly.
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Frail older adults have a higher total monocyte count than less frail older adults.
“It has been observed that there is an increased overall number of monocytes in frail older adults as compared to those les frail older adults (139).”
From The impact of ageing on monocytes and macrophages (2021) · cites this paper as [139]
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Frailty in Older Adults: Evidence for a Phenotype
Fried, L. P., Tangen, C. M., Walston, J., Newman, A. B., Hirsch, C., Gottdiener, J., Seeman, T., Tracy, R., Kop, W. J., Burke, G., et al. (2001) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/56.3.m146 · Cited by 24,907
Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases
Franceschi, C., & Campisi, J. (2014) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu057 · Cited by 3,891
A standard procedure for creating a frailty index
Searle, S. D., Mitnitski, A., Gahbauer, E. A., Gill, T. M., & Rockwood, K. (2008) · BMC Geriatrics · doi:10.1186/1471-2318-8-24 · Cited by 3,568
Role of C-Reactive Protein at Sites of Inflammation and Infection
Sproston, N. R., & Ashworth, J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00754 · Cited by 3,217
Accumulation of Deficits as a Proxy Measure of Aging
Mitnitski, A. B., Mogilner, A. J., & Rockwood, K. (2001) · The Scientific World JOURNAL · doi:10.1100/tsw.2001.58 · Cited by 2,893 · cited 1×
“Health status was defined by employing the concept of a frailty index (Mitnitski et al., 2001; Searle et al., 2008), which we also used in this study as an outcome measure.”
A comparison of two approaches to measuring frailty in elderly people
Rockwood, K., Andrew, M., & Mitnitski, A. (2007) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/62.7.738 · Cited by 1,291
Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines
Rea, I. M., Gibson, D. S., McGilligan, V., McNerlan, S. E., Alexander, H. D., & Ross, O. A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00586 · Cited by 1,267
Inflammation and frailty in the elderly: A systematic review and meta-analysis
Soysal, P., Stubbs, B., Lucato, P., Luchini, C., Solmi, M., Peluso, R., Sergi, G., Isik, A. T., Manzato, E., Maggi, S., et al. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.08.006 · Cited by 1,089
Gender differences in autoimmune disease
Ngo, S. T., Steyn, F. J., & McCombe, P. A. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.04.004 · Cited by 1,074
Inflammation: The Common Pathway of Stress-Related Diseases
Liu, Y.-Z., Wang, Y.-X., & Jiang, C.-L. (2017) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2017.00316 · Cited by 800
Sex differences in frailty: A systematic review and meta-analysis
Gordon, E. H., Peel, N. M., Samanta, M., Theou, O., Howlett, S. E., & Hubbard, R. E. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2016.12.021 · Cited by 686
Aging of the Immune System. Mechanisms and Therapeutic Targets
Weyand, C. M., & Goronzy, J. J. (2016) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201602-095aw · Cited by 586
Rockwood, K. J., Song, X., & Mitnitski, A. (2011) · Canadian Medical Association Journal · doi:10.1503/cmaj.101271 · Cited by 583
An update on inflamm-aging: mechanisms, prevention, and treatment
Xia, S., Zhang, X., Zheng, S., Khanabdali, R., Kalionis, B., Wu, J., Wan, W., & Tai, X. (2016) · Journal of Immunology Research · doi:10.1155/2016/8426874 · Cited by 538
Kulminski, A. M., Ukraintseva, S. V., Kulminskaya, I. V., Arbeev, K. G., Land, K., & Yashin, A. I. (2008) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2008.01656.x · Cited by 434
Collerton, J., Martin-Ruiz, C., Davies, K., Hilkens, C. M., Isaacs, J., Kolenda, C., Parker, C., Dunn, M., Catt, M., Jagger, C., et al. (2012) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2012.05.005 · Cited by 420
Inflamm-aging of hematopoiesis, hematopoietic stem cells, and the bone marrow microenvironment
Kovtonyuk, L. V., Fritsch, K., Feng, X., Manz, M. G., & Takizawa, H. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00502 · Cited by 371
Wertheimer, A. M., Bennett, M. S., Park, B., Uhrlaub, J. L., Martinez, C., Pulko, V., Currier, N. L., Nikolich-Žugich, D., Kaye, J., & Nikolich-Žugich, J. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1301721 · Cited by 352
The cellular composition of the human immune system is shaped by age and cohabitation
Carr, E. J., Dooley, J., Garcia‐Perez, J. E., Lagou, V., Lee, J. C., Wouters, C. H., Meyts, I., Goris, A., Boeckxstaens, G. E., Linterman, M. A., et al. (2016) · Nature Immunology · doi:10.1038/ni.3371 · Cited by 308
Baylis, D., Bartlett, D. B., Syddall, H. E., Ntani, G., Galé, C. R., Cooper, C. C., Lord, J. M., & Sayer, A. A. (2012) · AGE · doi:10.1007/s11357-012-9396-8 · Cited by 218
Dissociation of Pentameric to Monomeric C-Reactive Protein Localizes and Aggravates Inflammation
Thiele, J. R., Habersberger, J., Braig, D., Schmidt, Y., Goerendt, K., Maurer, V. J., Bannasch, H., Scheichl, A., Woollard, K. J., von Dobschütz, E., et al. (2014) · Circulation · doi:10.1161/circulationaha.113.007124 · Cited by 216
Cohort Profile: The Doetinchem Cohort Study
Verschuren, W. M. M., Blokstra, A., Picavet, H. S. J., & Smit, H. A. (2008) · International Journal of Epidemiology · doi:10.1093/ije/dym292 · Cited by 213
Goldszmid, R. S., & Trinchieri, G. (2012) · Nature Immunology · doi:10.1038/ni.2422 · Cited by 175
Khreiss, T., József, L., Hossain, S., Chan, J. S. D., Potempa, L. A., & Filep, J. G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205378200 · Cited by 167
Leng, S. X., Xue, Q., Tian, J., Huang, Y., Yeh, S.-H., & Fried, L. P. (2009) · Experimental Gerontology · doi:10.1016/j.exger.2009.05.005 · Cited by 164
Immunosenenescence: role of cytomegalovirus
Pawelec, G. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2013.11.010 · Cited by 163
Shen-Orr, S. S., Furman, D., Kidd, B. A., Hadad, F., Lovelace, P., Huang, Y.-W., Rosenberg-Hasson, Y., Mackey, S., Grisar, F. A. G., Pickman, Y., et al. (2016) · Cell Systems · doi:10.1016/j.cels.2016.09.009 · Cited by 154
Marcos-Pérez, D., Sánchez-Flores, M., Maseda, A., Lorenzo‐López, L., Millán-Calentí, J. C., Gostner, J. M., Fuchs, D., Pásaro, E., Laffón, B., & Valdiglesias, V. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01056 · Cited by 107
Vukmanovic-Stejic, M., Chambers, E. S., Suárez-Fariñas, M., Sandhu, D., Fuentes-Duculan, J., Patel, N., Agius, E., Lacy, K. E., Turner, C. T., Larbi, A., et al. (2018) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.10.032 · Cited by 103
Midlife Systemic Inflammation Is Associated With Frailty in Later Life: The ARIC Study
Walker, K. A., Walston, J., Gottesman, R. F., Kucharska-Newton, A., Palta, P., & Windham, B. G. (2019) · The Journals of Gerontology: Series A · doi:10.1093/gerona/gly045 · Cited by 91
Picavet, H. S. J., Blokstra, A., Spijkerman, A. M. W., & Verschuren, W. M. M. (2017) · International Journal of Epidemiology · doi:10.1093/ije/dyx103 · Cited by 78
van der Heiden, M., van Zelm, M. C., Bartol, S. J. W., de Rond, L., Berbers, G. A. M., Boots, A. M. H., & Buisman, A. (2016) · Scientific Reports · doi:10.1038/srep26892 · Cited by 59
Design of a frailty index among community living middle-aged and older people: The Rotterdam study
Schoufour, J. D., Erler, N. S., Jaspers, L., Jong, J. C. K., Voortman, T., Ziere, G. J., Lindemans, J. W., Klaver, C. C. W., Tiemeier, H. W., Stricker, B. H. C., et al. (2016) · Maturitas · doi:10.1016/j.maturitas.2016.12.002 · Cited by 45
Interventions to restore appropriate immune function in the elderly
Aspinall, R., & Lang, P. O. (2018) · Immunity & Ageing · doi:10.1186/s12979-017-0111-6 · Cited by 39
Hulsegge, G., Herber-Gast, G.-C. M., Spijkerman, A. M. W., Susan, H., Picavet, H. S. J., van der Schouw, Y. T., Bakker, S. J. L., Gansevoort, R. T., Dollé, M. E. T., Smit, H. A., et al. (2016) · Obesity · doi:10.1002/oby.21515 · Cited by 35
Influence of age, sex and HCMV-serostatus on blood lymphocyte subpopulations in healthy adults
Apoil, P. A., Puissant‐Lubrano, B., Congy‐Jolivet, N., Pérès, M., Tkaczuk, J., Roubinet, F., & Blancher, A. (2017) · Cellular Immunology · doi:10.1016/j.cellimm.2017.02.001 · Cited by 34
Tcherniaeva, I., den Hartog, G., Berbers, G. A. M., & van der Klis, F. R. M. (2018) · Journal of Immunological Methods · doi:10.1016/j.jim.2018.07.003 · Cited by 34
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The impact of ageing on monocytes and macrophages
De Maeyer, R. P. H., & Chambers, E. S. (2021) · Immunology Letters · doi:10.1016/j.imlet.2020.12.003 · Cited by 275
“It has been observed that there is an increased 528 overall number of monocytes in frail older adults as compared to those les frail older adults 529 (139).”
ResultSokołowska, M., Łukasik, Z. M., Agache, I. O., Akdiş, C. A., Akdiş, D., Akdiş, M., Barcik, W., Brough, H. A., Eiwegger, T., Eljaszewicz, A., et al. (2020) · Allergy · doi:10.1111/all.14462 · Cited by 170
Kuo, P.-L., Schrack, J. A., Shardell, M. D., Levine, M. E., Moore, A. Z., An, Y., Elango, P., Karikkineth, A. C., Tanaka, T., de Cabo, R., et al. (2020) · Journal of Internal Medicine · doi:10.1111/joim.13024 · Cited by 140
GDF15 as a biomarker of ageing
Liu, H., Huang, Y., Lyu, Y., Dai, W., Tong, Y., & Li, Y. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2021.111228 · Cited by 118
Ye, Y., Noche, R. B., Szejko, N., Both, C. P., Acosta, J., Leasure, A. C., Brown, S. C., Sheth, K. N., Gill, T. M., Zhao, H., et al. (2023) · GeroScience · doi:10.1007/s11357-023-00771-z · Cited by 98
“The discovery phase included 386,565 participants of European ancestry with complete data for frailty criteria from the UKB (mean age 57 years [SD 8], 208,481 (54”
BackgroundBiomarkers of aging in frailty and age-associated disorders: State of the art and future perspective
Salvioli, S., Basile, M. S., Bencivenga, L., Carrino, S., Conte, M., Damanti, S., LORENZO, R. D., Fiorenzato, E., Gialluisi, A., Ingannato, A., et al. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102044 · Cited by 90
Biomarkers of the ageing immune system and their association with frailty – A systematic review
Hoi, E. T. V., de Glas, N. A., Portielje, J. E. A., van Heemst, D., van den Bos, F., Jochems, S. P., & Mooijaart, S. P. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2023.112163 · Cited by 72
Inflammatory biomarkers of frailty: A review
Zhang, L., Zeng, X., He, F., & Huang, X. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2023.112253 · Cited by 75
Haschka, D., Tymoszuk, P., Bsteh, G., Petzer, V., Berek, K., Theurl, I., Berger, T., & Weiß, G. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00594 · Cited by 59
“Literature evidence indicates that gender, age, and overall physical status (frailty) may impact on proportions and numbers of circulating myeloid cells including the cell types differentially expanded in RRMSi in our study, like granulocytes (37, 38) and, intermediate and nonclassical monocytes (37– 41).”
BackgroundInflammatory marker trajectories associated with frailty and ageing in a 20‐year longitudinal study
Samson, L. D., Buisman, A., Ferreira, J. A., Picavet, H. S. J., Verschuren, W. M. M., Boots, A. M. H., & Engelfriet, P. M. (2022) · Clinical & Translational Immunology · doi:10.1002/cti2.1374 · Cited by 58
“For the present study, a subgroup of 144 people aged 65–75 years were selected from the DCS, stratified by sex and with equal numbers of participants classified as relatively healthy, frail or of intermediate health status, as described elsewhere.(7) In brief, the healthy ageing/frailty were defined as those with the…”
MethodResultInfluentialInflammation and cell-to-cell communication, two related aspects in frailty
Pansarasa, O., Mimmi, M. C., Davin, A., Giannini, M., Guaita, A., & Cereda, C. (2022) · Immunity & Ageing · doi:10.1186/s12979-022-00306-8 · Cited by 48
“Several studies reported a strong association of CRP plasma levels with frailty [16, 17].”
BackgroundTang, Y., Zhai, Y., Song, W., Zhu, T., Xu, Z., Jiang, L., Li, L., Liu, D., & Wu, Q. (2024) · Frontiers in Public Health · doi:10.3389/fpubh.2024.1427546 · Cited by 41
“Studies have shown that even in the absence of infection, frail older adults develop chronic low-grade inflammation over time (7, 8).”
BackgroundBruserud, Ø., Mosevoll, K. A., Bruserud, Ø., Reikvam, H., & Wendelbo, Ø. (2023) · Cells · doi:10.3390/cells12071003 · Cited by 38
Physiological Systems in Promoting Frailty
Perazza, L. R., Brown‐Borg, H. M., & Thompson, L. V. (2022) · Comprehensive physiology · doi:10.1002/cphy.c210034 · Cited by 66
“Recently, while investigating the immunological aspects of frailty higher numbers of myeloid-derived neutrophils and monocytes, but not lymphoid-derived T, B, or NK(natural killer)-cell numbers, were associated with frailty in both women and men (491).”
Terekhova, M., Boháčová, P., & Artyomov, M. N. (2025) · Immunity · doi:10.1016/j.immuni.2025.10.009 · Cited by 41
In-depth immune cellular profiling reveals sex-specific associations with frailty
Samson, L. D., Boots, A. M. H., Ferreira, J. A., Picavet, H. S. J., de Rond, L., de Zeeuw‐Brouwer, M., Verschuren, W. M. M., Buisman, A., & Engelfriet, P. M. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00191-z · Cited by 35
Energy metabolism and frailty: The potential role of exercise-induced myokines – A narrative review
Barros, D. G. M., Marques, E. A., Magalhães, J., & Carvalho, J. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101780 · Cited by 39
Gilmore, N. J., Mohile, S. G., Lei, L., Culakova, E., Mohamed, M., Magnuson, A. M., Loh, K. P., Maggiore, R. J., Belcher, E., Conlin, A. K., et al. (2021) · Breast Cancer Research · doi:10.1186/s13058-021-01388-w · Cited by 36
“Discussion In this secondary analysis of data from a nationwide, multi-center longitudinal cohort study, we confirmed the relationships between inflammation and frailty characteristics that have been reported in communitydwelling older adults as well as older adults with cancer over the age of 65 years [12, 14, 21].”
Frailty is related to serum inflammageing markers: results from the VITAL study
van Sleen, Y., Shetty, S. A., van der Heiden, M., Venema, M. C. A., Gutiérrez-Melo, N., Toonen, E. J. M., van Beek, J., Buisman, A., van Baarle, D., & Sauce, D. (2023) · Immunity & Ageing · doi:10.1186/s12979-023-00391-3 · Cited by 37
“IL-6 and CRP have often been proposed as potential markers of frailty [35–38].”
BackgroundLoeb, N., Andrew, M. K., Loeb, M. B., Kuchel, G. A., Haynes, L., McElhaney, J. E., & Verschoor, C. P. (2020) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofaa148 · Cited by 32
“Frailty is also known to be associated with increased numbers of monocytes [36], and the chemokine MCP1 [37], both of which have been hypothesized to support antibody responses to influenza vaccination [38, 39].”
BackgroundMerrill, S. M., Gladish, N., Fu, M. P., Moore, S. R., Konwar, C., Giesbrecht, G. F., MacIssac, J. L., Kobor, M. S., & Letourneau, N. L. (2021) · Attachment & Human Development · doi:10.1080/14616734.2021.1938872 · Cited by 34
Monocytes are the main source of STING-mediated IFN-α production
Congy‐Jolivet, N., Cénac, C., Dellacasagrande, J., Puissant‐Lubrano, B., Apoil, P. A., Guedj, K., Abbas, F., Laffont, S., Sourdet, S., Guyonnet, S., et al. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.104047 · Cited by 32
Samson, L. D., van den Berg, S. P. H., Engelfriet, P. M., Boots, A. M. H., Hendriks, M., de Rond, L., de Zeeuw‐Brouwer, M., Verschuren, W. M. M., Borghans, J. A. M., Buisman, A., et al. (2020) · Clinical & Translational Immunology · doi:10.1002/cti2.1193 · Cited by 30
“We did not find an association between frailty and CMV seroprevalence, or between frailty and duration of CMV infection, with frailty expressed by a frailty index score.(51) This is in line with some other papers,(29) although several studies showed a relation between CMV infection or CMV-specific antibody levels and…”
MethodResultInflammation as a risk factor for the development of frailty in the Lothian Birth Cohort 1936
Welstead, M., Terrera, G. M., Russ, T. C., Corley, J., Taylor, A. M., Galé, C. R., & Michelle Luciano, A. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.111055 · Cited by 30
“However, particularly in later life, chronic inflammation at low levels (inflamm-ageing) may develop even in the absence of infection (Samson et al., 2019).”
Effects of ageing and frailty on circulating monocyte and dendritic cell subsets
Reitsema, R. D., Kumawat, A. K., Hesselink, B.-C., van Baarle, D., & van Sleen, Y. (2024) · npj Aging · doi:10.1038/s41514-024-00144-6 · Cited by 29
“Previously, elevated frequencies of myeloid cells have been associated with frailty (14).”
Inflammatory Markers Associated with Physical Frailty and Cognitive Impairment
Pan, Y., & Ma, L. (2024) · Aging and Disease · doi:10.14336/ad.2024.0258 · Cited by 29
“Notably, the CRP levels in frail individuals have been reported to remain high for >10 years [109].”
New Pharmacological Tools to Target Leukocyte Trafficking in Lung Disease
Belchamber, K. B. R., Hughes, M., Spittle, D. A., Walker, E. M., & Sapey, E. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.704173 · Cited by 21
Autio, A., Nevalainen, T., Mishra, B. H., Jylhä, M. K., Flinck, H., & Hurme, M. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00182-0 · Cited by 22
“found that the numbers of neutrophils and monocytes increased with age, correlating with frailty and CRP trajectories [18].”
BackgroundThe complex role of neutrophils in healthy aging, inflammaging, and frailty
Abdullah, G. A., Akpan, A., Phelan, M. M., & Wright, H. L. (2025) · Journal of Leukocyte Biology · doi:10.1093/jleuko/qiaf117 · Cited by 21
Impaired JAK-STAT pathway signaling in leukocytes of the frail elderly
Samson, L. D., Engelfriet, P. M., Verschuren, W. M. M., Picavet, H. S. J., Ferreira, J. A., de Zeeuw‐Brouwer, M., Buisman, A., & Boots, A. M. H. (2022) · Immunity & Ageing · doi:10.1186/s12979-021-00261-w · Cited by 18
“The frailty index was calculated based on data of the last two DCS assessment rounds (round 5 and 6) and was validated in the Doetinchem cohort study [33].”
MethodInflammatory markers and frailty in home-dwelling elderly, a cross-sectional study
Bålsrud, P., Ulven, S. M., Christensen, J. J., Ottestad, I. O., & Holven, K. B. (2024) · BMC Geriatrics · doi:10.1186/s12877-024-04690-2 · Cited by 17
“Another study showed an association between CRP trajectories over a follow-up time of more than 15 years and FI, in subjects aged 60–85 at endpoint [10].”
BackgroundResultMaeyer, R. P. H. D., Sikora, J., Bracken, O. V., Shih, B. B.-J., Lloyd, A. F., Peckham, H., Hollett, K., Abdelhamid, K., Cai, W., James, M., et al. (2025) · Aging Cell · doi:10.1111/acel.70249 · Cited by 15
“This process underlies age-associated pathologies including frailty (Samson et al. 2019), neurodegeneration (Weaver et al. 2002) and mortality (Bruunsgaard et al. 2003; Giovannini et al. 2011; Furman et al. 2017), and is linked to poor vaccine efficacy (Parmigiani et al. 2013; Fourati et al. 2016).”
Guan, L., Liu, Q., Yao, Y., Wang, L., Yang, P., Chen, S., Zhou, L., & Zheng, X. (2022) · Experimental Gerontology · doi:10.1016/j.exger.2022.111955 · Cited by 15
Immunotherapy use in older adults with cancer with frailty: A young SIOG review paper
Güven, D. C., Martínez-Cannon, B. A., Testa, G. D., Martins, J. C., Velasco, R., Kalsi, T., & Gomes, F. (2024) · Journal of Geriatric Oncology · doi:10.1016/j.jgo.2024.101742 · Cited by 14
Biomarkers of Senescence during Aging as Possible Warnings to Use Preventive Measures
Gasmi, A., Chirumbolo, S., Peana, M., Mujawdiya, P. K., Dadar, M., Menzel, A., & Bjørklund, G. (2020) · Current Medicinal Chemistry · doi:10.2174/0929867327999200917150652 · Cited by 14
Biomarkers of frailty: Moving the field forward
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Mosevoll, K. A., Hansen, B., Gundersen, I. M., Reikvam, H., Bruserud, Ø., Bruserud, Ø., & Wendelbo, Ø. (2023) · Biomolecules · doi:10.3390/biom13020223 · Cited by 10
Scale-based screening and assessment of age-related frailty
Wang, X., Zhang, Y.-H., Meng, C., Fan, L., Wei, L., Li, Y., Liu, X., & Lv, S. (2024) · Frontiers in Public Health · doi:10.3389/fpubh.2024.1424613 · Cited by 11
Romeo, F. J., Seropian, I. M., Chiabrando, J. G., Raleigh, J. V., Smietniansky, M., Cal, M., Falconi, M. L., Kotowicz, V., Agatiello, C. R., & Berrocal, D. H. (2020) · Catheterization and Cardiovascular Interventions · doi:10.1002/ccd.29067 · Cited by 12
Noh, J. Y., Han, H. W., Kim, D. M., Giles, E. D., Farnell, Y. Z., Wright, G. A., & Sun, Y. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1357444 · Cited by 11
Kuijpers, Y., Picavet, H. S. J., de Rond, L., de Zeeuw‐Brouwer, M., Rutkens, R., Gijsbers, E. F., Slits, I., Engelfriet, P. M., Buisman, A., & Verschuren, W. M. M. (2023) · Immunity & Ageing · doi:10.1186/s12979-023-00382-4 · Cited by 9
“This frailty index is a measure consisting of 36 ‘deficits’ defined based on chronic conditions, cognitive, physical, and psychological functioning as described before [30].”
Natural killer cells immunosenescence and the impact of lifestyle management
Wang, L., Mao, L., Xiao, W., & Chen, P. (2023) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2023.149216 · Cited by 8
The Role of Inflammatory and Cytokine Biomarkers in the Pathogenesis of Frailty Syndrome
Mir, R., Jha, C. K., Khullar, N., Maqbool, M., Dabla, P. K., Mathur, S., Moustafa, A., Faridi, U. A., Hamadi, A., Mir, R., et al. (2022) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530322666220304220522 · Cited by 7
Kuijpers, Y., Kaczorowska, J., Picavet, H. S. J., de Zeeuw‐Brouwer, M., Kuijer, M., Slits, I., Gijsbers, E. F., Rutkens, R., de Rond, L., Verschuren, W. M. M., et al. (2024) · Immunity & Ageing · doi:10.1186/s12979-024-00476-7 · Cited by 5
“The frailty index was calculated, consisting of 36 ‘defi-cits’ defined based on chronic conditions, cognitive, physical, and psychological functioning all of which were included in previous frailty indexes as described before [13].”
MethodAge- and comorbidity-stratified clinical profiles of hospitalized chikungunya patients, China, 2025
Ren, Z., Samba, F. M., Lv, G., Kang, F., Li, Y., Gao, Q., Lin, Q., Hong, Z., Wan, S., Lu, S., et al. (2026) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2026.108368 · Cited by 3
In-depth human immune cellular profiling from newborn to frail
Li, W., Liu, H., Gao, L., Hu, Y., Zhang, A., Li, W., Liu, G., Bai, W., Xu, Y., Xiao, C., et al. (2024) · Journal of Leukocyte Biology · doi:10.1093/jleuko/qiae046 · Cited by 3
Kuiper, L. M., Picavet, H. S. J., Rietman, M. L., Dollé, M. E. T., & Verschuren, W. M. M. (2024) · The Journals of Gerontology Series A · doi:10.1093/gerona/glae272 · Cited by 3
Pre‐Vaccination Immunotypes and Immune Entropy Are Indicators of Multiple Vaccine Responsiveness
Çevirgel, A., van der Heiden, M., Shetty, S. A., Viljanen, M., Vos, M. W., Bijvank, E., van Sleen, Y., Imhof, C., Rolwes, J. A. J., Samson, L. D., et al. (2025) · Aging Cell · doi:10.1111/acel.70151 · Cited by 7
“…the association between immune entropy and vaccine response, we next assessed immune entropy in a different cohort of older individuals who were previously immune phenotyped using a similar panel of markers as used in the VITAL cohort (Samson, AM, et al. 2020; Samson et al. 2019) (Figure S1b).”
de Sousa, A. R. S., Ottestad, I. O., Gjevestad, G. O., Holven, K. B., Ulven, S. M., & Christensen, J. J. (2023) · GeroScience · doi:10.1007/s11357-023-00819-0 · Cited by 4
“While there are disagreeing reports regarding the numbers of circulating monocytes in older age [34, 35], increased numbers of circulating monocytes have been detected in frail older adults versus healthy older participants [17].”
BackgroundBaseline immunotypes and immune entropy are indicators of multiple vaccine responsivenessPreprint
Çevirgel, A., van der Heiden, M., Shetty, S. A., Viljanen, M., Vos, M. W., Bijvank, E., van Sleen, Y., Imhof, C., Rolwes, J. A. J., Samson, L. D., et al. (2024) · medRxiv · doi:10.1101/2024.05.29.24308098 · Cited by 3
“To validate the association between immune entropy and vaccine response, we next assessed immune entropy in a different cohort of older individuals who were previously immune phenotyped using a similar panel of markers as used in the VITAL cohort 27,28 (Supplementary Figure 1b).”
MethodBakır, B., Şahin, H., Kaner, G., Kar, H., & Dılek, O. N. (2025) · Irish Journal of Medical Science (1971 -) · doi:10.1007/s11845-025-04060-w · Cited by 2
“Samson et al. [56] also reported chronic low-grade inflammation in frail elderly individuals for more than 15 years.”
Vargas, A., Holub, K., & Biete, A. (2022) · Clinical & Translational Oncology · doi:10.1007/s12094-022-02836-5 · Cited by 2
“Several studies have found a relationship between frailty and high leucocyte, neutrophil and monocyte counts [17, 18].”
BackgroundImpaired JAK-STAT Pathway Signaling in Leukocytes of Frail ElderlyPreprint
Samson, L. D., Engelfriet, P. M., Verschuren, W. M. M., Picavet, H. S. J., Ferreira, J. A., de Zeeuw‐Brouwer, M., Buisman, A., & Boots, A. M. H. (2021) · Research Square · doi:10.21203/rs.3.rs-970801/v1 · Cited by 2
McIntosh, R. C. (2024) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2024.100940 · Cited by 1
“In a landmark study, the presence of chronic elevated myeloid cells over more than 15 years outperformed lymphoid derived T, B, or NK-cell numbers in predicting an index of frailty based upon 36 health parameters (Samson et al., 2019).”
Cognitive Frailty Classification Models for Older Adults in a Point-of-Care System
Cao, L., Lim, Y. W., Tan, M. P., & Rokhani, F. Z. (2024) · IEEE Asia Pacific Conference on Circuits and Systems (APCCAS) · doi:10.1109/apccas62602.2024.10808371 · Cited by 1
“Neutrophil dysfunction is also associated with CF, but few studies have considered total neutrophil count which is a far easier parameter to measure, and neutrophil count has been found to be associated with frailty [21], [22].”
Volkos, P., Linardakis, M. K., & Symvoulakis, E. K. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14124236 · Cited by 2
“Additionally, higher CRP levels were associated with the prediction of 12 cancer types, according to the results of a cohort study [4]; meanwhile, in another cohort, higher CRP levels were found among the frail group (compared to healthy and in-between groups) [5].”
Relation of inflammatory marker trajectories with frailty and aging in a 20-year longitudinal studyPreprint
Samson, L. D., Buisman, A., Ferreira, J. A., Picavet, H. S. J., Verschuren, W. M. M., Boots, A. M. H., & Engelfriet, P. M. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.02.10.430670 · Cited by 1
GDF-15 as a biomarker of agingPreprint
Liu, H., Huang, Y., Lyu, Y., Dai, W., Tong, Y., & Li, Y. (2020) · doi:10.21203/rs.3.rs-30717/v1 · Cited by 1
“In patients with frailty, a higher number of monocytes is associated with frailty [33].”
BackgroundImpact of cytomegalovirus-infection on ageing of the immune system
Berg, S. (2020) · Utrecht University Repository (Utrecht University) · doi:10.33540/66
Ageing Mucosal Immunity and Its Consequences for Infectious Diseases in the Aged; A First Glance
van der Heiden, M., & van Baarle, D. (2021) · Healthy ageing and longevity · doi:10.1007/978-3-030-87532-9_6
Additional file 1 of Frailty is related to serum inflammageing markers: results from the VITAL study
van Sleen, Y., Shetty, S. A., van der Heiden, M., Venema, M. C. A., Gutiérrez-Melo, N., Toonen, E. J. M., van Beek, J., Buisman, A., van Baarle, D., & Sauce, D. (2023) · Figshare · doi:10.6084/m9.figshare.24647129
Kuijpers, Y., Picavet, H. S. J., de Rond, L., de Zeeuw-Brouwer, M.-L., Rutkens, R., Gijsbers, E. F., Slits, I., Engelfriet, P. M., Buisman, A., & Verschuren, W. M. M. (2024) · Figshare · doi:10.6084/m9.figshare.26631592
Kuijpers, Y., Picavet, H. S. J., de Rond, L., de Zeeuw-Brouwer, M.-L., Rutkens, R., Gijsbers, E. F., Slits, I., Engelfriet, P. M., Buisman, A., & Verschuren, W. M. M. (2024) · Figshare · doi:10.6084/m9.figshare.26631595
Additional file 3 of Inflammation and cell-to-cell communication, two related aspects in frailty
Pansarasa, O., Mimmi, M. C., Davin, A., Giannini, M., Guaita, A., & Cereda, C. (2022) · Figshare · doi:10.6084/m9.figshare.21405916
Kuijpers, Y., Picavet, H. S. J., de Rond, L., de Zeeuw-Brouwer, M.-L., Rutkens, R., Gijsbers, E. F., Slits, I., Engelfriet, P. M., Buisman, A., & Verschuren, W. M. M. (2024) · Figshare · doi:10.6084/m9.figshare.26631586
Bålsrud, P., Ulven, S. M., Christensen, J. J., Ottestad, I. O., & Holven, K. B. (2024) · Figshare · doi:10.6084/m9.figshare.25248781
Kuijpers, Y., Picavet, H. S. J., de Rond, L., de Zeeuw-Brouwer, M.-L., Rutkens, R., Gijsbers, E. F., Slits, I., Engelfriet, P. M., Buisman, A., & Verschuren, W. M. M. (2024) · Figshare · doi:10.6084/m9.figshare.26631589
Kuijpers, Y., Picavet, H. S. J., de Rond, L., de Zeeuw-Brouwer, M.-L., Rutkens, R., Gijsbers, E. F., Slits, I., Engelfriet, P. M., Buisman, A., & Verschuren, W. M. M. (2024) · Figshare · doi:10.6084/m9.figshare.26631598
Autio, A., Nevalainen, T., Mishra, B. H., Jylhä, M., Flinck, H., & Hurme, M. (2020) · Figshare · doi:10.6084/m9.figshare.12299504
Kuijpers, Y., Picavet, H. S. J., de Rond, L., de Zeeuw-Brouwer, M.-L., Rutkens, R., Gijsbers, E. F., Slits, I., Engelfriet, P. M., Buisman, A.-M., & Verschuren, W. M. M. (2024) · Figshare · doi:10.6084/m9.figshare.26631601
Deng, P., Cao, Z., Yan, S., & Lu, J. (2026) · Maturitas · doi:10.1016/j.maturitas.2026.108984
Ma, X., Liu, N., Wu, X., Chen, Q., Chen, X. J., Zhou, Q., Chen, S., Lin, Y., & Wang, X. L. (2026) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.70273 · Cited by 2
Visser, M., Kuijpers, Y., Tcherniaeva, I., van Rooijen, D. M., de Rond, L., de Zeeuw‐Brouwer, M., Marinović, A. B., Richardson, H., Mulvihill, K. M., Goldblatt, D., et al. (2026) · Immunity & Ageing · doi:10.1186/s12979-026-00573-9
“In addition, frailty was quantified using a validated frailty index developed within the DCS, based on 36 physical, cognitive, and psychological health parameters, ranging from 0 (completely non-frail) to 1 (completely frail) [29].”
InfluentialPicavet, H. S. J., Rietman, M. L., Blokstra, A., & Verschuren, W. M. M. (2026) · International Journal of Epidemiology · doi:10.1093/ije/dyag120
“This was used to study which aspects of the ageing immune system are most relevant in the process of reaching old age in good health [13].”
Xu, T., & Fernandez‐Medina, T. (2026) · International Journal of Dentistry · doi:10.1155/ijod/8562785
“…characteristics from various donors indicated that age and gender did not signi fi cantly determine cell yield recovery or protein content, consistent with studies showing no association between age and neutrophil number [47, 48] and no signi fi cant differences in plasma protein content [49].”
Cao, J., Yang, Z., Mou, R., Yang, P., Liu, W., & Jia, Y. (2026) · Nutrire · doi:10.1186/s41110-026-00521-z
“Consistent with this, previous studies have shown that sarcopenia and frailty are associated with low hemoglobin, hypoalbuminemia, and elevated CRP [ 8–10], while anemia and hypoalbuminemia are well-recognized clinical manifestations of malnutrition [11 ].”
Metadata
- Authors
- Samson, L. D., Boots, A. M. H., Verschuren, W. M. M., Picavet, H. S. J., Engelfriet, P., & Buisman, A.-M.
- Affiliations
- University Medical Center Groningen (NL)
- University Medical Center Utrecht (NL)
- National Institute for Public Health and the Environment (NL)
- Corresponding author
- Samson, Leonard Daniël
- ORCID
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 125
- Pages
- 110674
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W2963643883
- Cited by
- 77
- References
- 37
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 20 · 2023: 11 · 2022: 11 · 2021: 7 · 2020: 15
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Experimental Gerontology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by-nc-nd)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Rivm Repository (Netherlands National Institute for Public Health and the Environment) (submittedVersion)
- Rivm (National Institute for Public Health and the Environment) (submittedVersion)
- Rivm (National Institute for Public Health and the Environment) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- Ministerie van Volksgezondheid, Welzijn en Sport
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
- Keywords
- frailty, C-reactive protein, low-grade inflammation, neutrophils, monocytes, myeloid cell expansion, immunosenescence, aging, frailty index, CMV serostatus, lymphocyte subsets, older adults, sex differences
- MeSH terms
- Frailty, Aged, Aged, 80 and over, Aging, C-Reactive Protein, Female, Humans, Inflammation, Leukocyte Count, Male, Middle Aged, Retrospective Studies, Sex Factors
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