Cited by 754Aging and Gerontology ResearchGenetics, Aging, and Longevity in Model OrganismsT-cell and B-cell Immunology

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Admission criteria for immunogerontological studies in man: The senieur protocol

Ligthart, Gerard J., Corberand, Joël X., Fournier, Catherine, Galanaud, Pierre, Hijmans, Willy, Kennes, Bernard, Müller-Hermelink, Hans K., Steinmann, Gerhard G.·1984·Mechanisms of Ageing and Development

DOI 10.1016/0047-6374(84)90152-0

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Abstract

Immunogerontological studies in man have often led to conflicting results. One of the main reasons is the selection of the subjects to be studied. Admission criteria such as "apparently healthy" or "without overt disease" seem insufficient to exclude underlying disease which might influence the immune system and thereby the results. In an attempt to solve this problem, the SENIEUR protocol described in this paper was developed by a working party in the framework of the EURAGE Concerted Action Programme on Ageing of the European Community. This protocol establishes strict admission criteria for immunogerontological studies in man based on clinical information and laboratory data, and it sets limits to pharmacological interference. The use of this protocol will lead to standardization between centers and also to a closer study of the influence of age as such on the immune system. These findings in the immunologically "optimally aged" can also serve as reference values for immunogerontological studies in subjects who do not meet the SENIEUR criteria. In this way the use of this protocol can contribute to the dissection of the influence of disease versus ageing on the immune system.

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Influential
Role of Phosphoinositide 3-Kinase and Extracellular Signal-Regulated Kinase Pathways in Granulocyte Macrophage-Colony-Stimulating Factor Failure to Delay Fas-Induced Neutrophil Apoptosis in Elderly Humans
Tortorella, C., Simone, O., Piazzolla, G., Stella, I., Cappiello, V., & Antonaci, S. (2006) · The Journals of Gerontology Series A · doi:10.1093/gerona/61.11.1111 · Cited by 51
“Donors Thirty volunteers (16 men and 14 women) older than 65 years (mean age, 79 years; range, 72–94 years), free from diseases affecting the immune system, cancer, or infections and taking no antiinflammatory drugs or corticosteroids, were selected according to the SENIEUR protocol (30).”
Method
Comorbidities associated with higher von Willebrand factor ( VWF ) levels may explain the age‐related increase of VWF in von Willebrand disease
Atiq, F., Meijer, K., Eikenboom, J. C. J., Fijnvandraat, K., Mauser‐Bunschoten, E. P., van Galen, K. P. M., Nijziel, M. R., Ypma, P. F., de Meris, J., Gorkom, B. A. P. L., et al. (2018) · British Journal of Haematology · doi:10.1111/bjh.15277 · Cited by 51
“However, they defined “healthy” based on the Senieur Protocol in which some disorders, including thyroid dysfunction, is defined as healthy (Ligthart et al, 1984).”
Background
The impaired immune response to diphtheria vaccinationin elderly chronic hemodialysis patients is related to zinc deficiency
Kreft, B., Fischer, A., Krüger, S., Sack, K., Kirchner, H., & Rink, L. (2000) · Biogerontology · doi:10.1023/a:1010077622172 · Cited by 51
“The reduced serum zinc level in hemodialysis patients seems to be age-related and without pathologic significance, since the control goup of elderly volunteers fulfilled all criteria of the immunogerontological SENIEURprotocol for health (Ligthart et al. 1984).”
BackgroundMethodInfluential
Effect of improved zinc status on T helper cell activation and TH1/TH2 ratio in healthy elderly individuals
Kahmann, L., Uciechowski, P., Warmuth, S., Malavolta, M., Mocchegiani, E., & Rink, L. (2006) · Biogerontology · doi:10.1007/s10522-006-9058-2 · Cited by 51
“Selecting subjects for gerontological studies according to the SENIEUR protocol made it possible to determine age-related alterations in immune function and to differentiate it from other influencing factors like diseases (Ligthart et al. 1984).”
Background
Age-related tyrosine-specific protein phosphorylation defect in human T lymphocytes activated through CD3, CD4, CD8 or the IL-2 receptor
Quadri, R. A., Plastre, O., Phelouzat, M.-A., Arbogast, A., & Proust, J. J. (1996) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(96)01715-0 · Cited by 51
Ambulatory Monitoring of Sleep‐Wakefulness Patterns in Healthy Elderly Males and Females (>88 Years): The “Senieur” Protocol
Wauquier, A., van Sweden, B., Lagaay, A. M., Kemp, B., & KAMPHUISEN, H. A. C. (1992) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1992.tb01928.x · Cited by 51
HCV antibodies in saliva and urine
Elsana, S., Sikuler, E., Yaari, A., Shemer‐Avni, Y., Abu‐Shakra, M., Buskila, D., Katzman, P., Naggan, L., & Margalith, M. (1998) · Journal of Medical Virology · doi:10.1002/(sici)1096-9071(199805)55:1 · Cited by 46
Self-citation
Cyclodextrin modulation of T lymphocyte signal transduction with aging
Fülöp, T., Douziech, N., Goulet, A.-C., Desgeorges, S., Linteau, A., Lacombe, G., & Dupuis, G. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00274-3 · Cited by 49
Apolipoprotein E alleles in nonagenarian subjects in the Belfast Elderly Longitudinal Free-living Ageing Study (BELFAST)
Rea, I. M., Dowell, I. M., McMaster, D., Smye, M., Stout, R. L., & Evans, A. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00278-0 · Cited by 49
Effect of Resistance Training on Immunological Parameters of Healthy Elderly Women
Raso, V., Benard, G., Duarte, A. J. D. S., & Natale, V. M. (2007) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e318156e9fa · Cited by 48
“current and past detailed health status; (II) 12-lead electrocardiogram; (III) cardiopulmonary exercise testing; (IV) body composition by bioelectrical impedance technique; and (V) laboratory parameters according to the SENIEUR protocol (19).”
Method
Anti-beta 2 glycoprotein I antibodies in centenarians
Meroni, P. L., Mari, D., Monti, D., Coppola, R., Capri, M., Salvioli, S., Tincani, A., Gerli, R., & Franceschi, C. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.08.003 · Cited by 48
“3 years (group 4)] selected according to the SENIEUR Protocol (Ligthart et al., 1984).”
Method
Association between Changes in Adrenal Secretion and Cerebral Morphometric Correlates in Normal Aging and Senile Dementia
Magri, F., Terenzi, F., Ricciardi, T., Fioravanti, M., Solerte, S. B., Stabile, M., Balza, G., Gandini, C., Villa, M., & Ferrari, E. (2000) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000017220 · Cited by 48
Aging and Impairment of Innate Immunity
Nomellini, V., Gómez, C. R., & Kovacs, E. J. (2008) · KARGER eBooks · doi:10.1159/000136358 · Cited by 47
Contribution of zinc to reduce CD4+ risk factor for ‘severe’ infection relapse in aging: parallelism with HIV
Mocchegiani, E., Muzzioli, M., Gaetti, R., Veccia, S., Viticchi, C., & Scalise, G. (1999) · International Journal of Immunopharmacology · doi:10.1016/s0192-0561(99)00009-0 · Cited by 47
“Five men and ten women healthy elderly subjects (672 4.6 years) were recruited in accordance to immunogerontological `SENIEUR protocol' (Ligthart et al., 1984).”
MethodInfluential
TREM2 expression and amyloid‐beta phagocytosis in Alzheimer's disease
La Rosa, F., Agostini, S., Piancone, F., Marventano, I., Hernis, A., Fenoglio, C., Galimberti, D., Scarpini, E., Saresella, M., & Clerici, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108626 · Cited by 50
“Twelve sex and age-matched healthy controls (HC) were enrolled as well in the study; these individuals were volunteers without a family history of dementia or evidence of acute or chronic neurologic diseases at the time of enrollment and were selected according to the SENIEUR protocol for immuno-gerontological studies…”
Method
Impairment of the ABCA1 and SR-BI-mediated cholesterol efflux pathways and HDL anti-inflammatory activity in Alzheimer's disease
Khalil, A., Berrougui, H., Pawelec, G., & Fülöp, T. (2011) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2011.11.008 · Cited by 46
“cal studies (Ligthart et al., 1984).”
B cell subsets in postmenopausal women and the effect of hormone replacement therapy
Kamada, M., Irahara, M., Maegawa, M., Yasui, T., Yamano, S., Yamada, M., Tezuka, M., Kasai, Y., Deguchi, K., Ohmoto, Y., et al. (2001) · Maturitas · doi:10.1016/s0378-5122(00)00180-8 · Cited by 46
“Subjects who contracted infectious diseases, inflammatory disorders, malignancy, autoimmune diseases, malnutrition, alcoholism or drug abuse were excluded according to the SENIEUR protocol [14].”
Method
Hemorheological changes and overproduction of cytokines from immune cells in mild to moderate dementia of the Alzheimer’s type: adverse effects on cerebromicrovascular system.
Solerte, S. B., Ceresini, G., Ferrari, E., & Fioravanti, M. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00105-6 · Cited by 46
IgE regulation and lymphokine patterns in aging humans
Al-Rayes, H., Pachas, W. N., Mirza, N., Ahern, D., Geha, R. S., & Vercelli, D. (1992) · Journal of Allergy and Clinical Immunology · doi:10.1016/0091-6749(92)90136-p · Cited by 46
Age-associated changes in mitochondrial parameters on peripheral human lymphocytes
Drouet, M., Lauthier, F., Charmes, J. P., Sauvage, P., & Ratinaud, M. (1999) · Experimental Gerontology · doi:10.1016/s0531-5565(99)00058-3 · Cited by 46
Neutrophils of healthy aged humans are normal
Corberand, J. X., Laharrague, P. F., & Fillola, G. (1986) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(86)90138-7 · Cited by 46
Self-citation
Peripheral blood dendritic cells reinduce proliferation in in vitro aged T cell populations
Steger, M. M., Maczek, C., & Grubeck-Loebenstein, B. (1997) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(96)01835-0 · Cited by 45
Introduction: The Reshaping of the Immune System with Age
Franceschi, C., & Cossarizza, A. (1995) · International Reviews of Immunology · doi:10.3109/08830189509056697 · Cited by 45
A marked drop in the incidence of the null allele of the B gene of the fourth component of complement (C4B*Q0) in elderly subjects: C4B*Q0 as a probable negative selection factor for survival
Krámer, J., F�l�p, T., Rajczy, K., Tuan, N., & F�st, G. (1991) · Human Genetics · doi:10.1007/bf00201547 · Cited by 44
“C4B,Q0 occurred in series i ( Kramer et al. 1989c ) and series 2 in 18.5% and 17.2% of the "young" men and in 1.8% and 4.0% of the "old" men, respectively.”
BackgroundInfluential
Reductions in the Activation of ERK and JNK Are Associated with Decreased IL-2 Production in T Cells from Elderly Humans Stimulated by the TCR/CD3 Complex and Costimulatory Signals
Beiqing, L., Carle, K. W., & Whisler, R. L. (1997) · Cellular Immunology · doi:10.1006/cimm.1997.1226 · Cited by 44
DNA sequence changes in aging: How frequent, how important?
Vijg, J. (1990) · Aging Clinical and Experimental Research · doi:10.1007/bf03323904 · Cited by 44
Translational research in immune senescence: Assessing the relevance of current models
High, K. P., Akbar, A. N., & Nikolich‐Žugich, J. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.04.007 · Cited by 42
Regulatory role of extracellular matrix proteins in neutrophil respiratory burst during aging
Tortorella, C., Piazzolla, G., Spaccavento, F., Vella, F., Pace, L., & Antonaci, S. (2000) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(00)00171-8 · Cited by 43
TOTAL SERUM IL-12 AND IL-12p40, BUT NOT IL-12p70, ARE INCREASED IN THE SERUM OF OLDER SUBJECTS; RELATIONSHIP TO CD3+AND NK SUBSETS
Rea, I. M., McNerlan, S., & Alexander, H. D. (2000) · Cytokine · doi:10.1006/cyto.1999.0537 · Cited by 43
Different rates of telomere shortening and telomerase activity reduction in CD8 T and CD16 NK lymphocytes with ageing
Mariani, E. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(03)00058-5 · Cited by 43
During a corticotropin-releasing hormone test in healthy subjects, administration of a beta-adrenergic antagonist induced secretion of cortisol and dehydroepiandrosterone sulfate and inhibited secretion of ACTH
Kizildere, S., Glück, T., Zietz, B., Schölmerich, J., & Straub, R. H. (2003) · European Journal of Endocrinology · doi:10.1530/eje.0.1480045 · Cited by 41
Age-related changes in the natural killer cell response to seasonal influenza vaccination are not influenced by a synbiotic: A randomised controlled trial
Przemska-Kosicka, A., Childs, C. E., Maidens, C., Dong, H., Todd, S., Gosney, M. A., Tuohy, K. M., & Yaqoob, P. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00591 · Cited by 43
“Additional exclusion criteria for older volunteers included: laboratory data which were outside the normal range for this age group AND outside the ranges speci fi ed in the SENIEUR protocol (27), Barthel Index score of < 16/100, cumulative illness rating scale score of > 15 (28).”
Production of antimicrobial peptides is preserved in aging
Castañeda‐Delgado, J. E., Miranda-Castro, N. Y., González‐Amaro, R., Gonzalez-Curiel, I. E., Montoya-Rosales, A., Rivas-Calderon, B., & Rivas-Santiago, B. T. (2013) · Clinical Immunology · doi:10.1016/j.clim.2013.05.015 · Cited by 42
Multidimensional evaluation of endogenous and health factors affecting food preferences, taste and smell perception
Guido, D., Perna, S., Carrai, M., Barale, R., Grassi, M., & Rondanelli, M. (2016) · The journal of nutrition health & aging · doi:10.1007/s12603-016-0703-4 · Cited by 42
“Subjects over 65 were eligible if they had the characteristics shown in Senieur Protocol (38).”

Authors: Ligthart, G. J., Corberand, J. X., Fournier, C., Galanaud, P., Hijmans, W., Kennes, B., Müller-Hermelink, H. K., & Steinmann, G. G.
Affiliations: Leiden University (NL)
Hôpital Necker-Enfants Malades (FR)
Université Paris-Sud (FR)
Christian-Albrechts-Universität zu Kiel (DE)
Corresponding author: Ligthart, Gerard J.
ORCID: Galanaud, Pierre
Venue: Mechanisms of Ageing and Development
Publisher: Elsevier BV
Published: 1984-11
Volume: 28
Issue: 1
Pages: 47-55
ISSN: 0047-6374 (ISSN-L)
DOI: 10.1016/0047-6374(84)90152-0
OpenAlex: W2037412303
Cited by: 754
References: 9
Citations by year: 2026: 2 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 6 · 2021: 9 · 2020: 10 · 2019: 11 · 2018: 13 · 2017: 8 · 2016: 17 · 2015: 11 · 2014: 11 · 2013: 22 · 2012: 18
FWCI: 13.79
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Mechanisms of Ageing and Development (publishedVersion)
PubMed (publishedVersion)
Topics: Social Sciences › Psychology › Developmental and Educational Psychology › Aging and Gerontology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: healthy aging, reference values, age-related immune changes
MeSH terms: Adult, Aged, Aging, Cardiovascular Diseases, Humans, Immunity, Infections, Inflammation, Lymphoproliferative Disorders, Neoplasms, Research Design

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Admission criteria for immunogerontological studies in man: The senieur protocol

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