Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

npj Aging
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. npj aging
  3. articles
  4. article

For urgent queries, please contact the Journal Publisher, Aicha Hanna.

Biological age and immunosenescence in Colombian centenarians
Download PDF
Download PDF
  • Article
  • Open access
  • Published: 16 February 2026

Biological age and immunosenescence in Colombian centenarians

  • Juan-Manuel Anaya1,2,
  • Edward A. Ruiz-Narváez3,
  • Ivan David Lozada-Martinez1,2,
  • Manuel Rojas1,4,5,
  • Diana M. Monsalve1,4,
  • Jesús Armando Álvarez-Álvarez1,6,
  • María José Díaz Gutiérrez1,7,
  • Olianis Pájaro1,7,
  • Brenda Guerra1,7,
  • Juan Esteban Gallo1,8,
  • Isaura Torres1,8,9,
  • Carolina Ramírez-Santana1,4,
  • Andres Angelo Cadena Bonfanti1,7,10 &
  • …
  • Yeny Acosta-Ampudia1,4 

npj Aging , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Biomarkers
  • Diseases
  • Immunology
  • Medical research

Abstract

Biological aging and immunosenescence are central to longevity, yet their interplay in centenarians remains unclear. We conducted a cross-sectional study in 160 Colombian centenarians to examine associations between biological age (PhenoAge), immunosenescence and age-related clinical variables. Cytokine profiling (n = 114) and lymphocyte immunophenotyping (n = 42) were assessed. It was observed that better QoL and well-being were significantly associated with lower biological age, while depressive symptoms, prior tobacco use, elevated levels of RANTES and G-CSF as well as a distinct CD8+ T cell phenotype including greater CD27− CD28+ central memory, effector memory, and KLRG1− CD57+ terminally differentiated effector memory T cells (TEMRA), and fewer KLRG1+ CD57+ TEMRA cells were linked to higher biological age. Centenarians were classified into three categories: vigorous (10%), resilient (46.25%), and vulnerable (43.75%). Cytokine levels were similar across the groups. These findings challenge the notion of immunosenescence in centenarians and highlight the value of translational research in geroscience.

Data availability

Individual-level data cannot be stored in public repositories or otherwise made publicly available due to ethical and data protection restrictions. However, data are available upon request for researchers who meet the criteria for access to confidential data.

References

  1. Cohen, A. A. et al. A complex systems approach to aging biology. Nat. Aging 2, 580–591 (2022).

    Google Scholar 

  2. Giuliani, C. et al. Centenarians as extreme phenotypes: An ecological perspective to get insight into the relationship between the genetics of longevity and age-associated diseases. Mech. Ageing Dev. 165, 195–201 (2017).

    Google Scholar 

  3. Mak, J. et al. Clinical biomarker-based biological aging and risk of cancer in the UK Biobank. Br. J. Cancer 129, 94–103 (2023).

    Google Scholar 

  4. Bortz, J. et al. Biological age estimation using circulating blood biomarkers. Commun. Biol. 6, 1089 (2023).

    Google Scholar 

  5. Terekhova, M., Bohacova, P. & Artyomov, M. N. Human immune aging. Immunity 58, 2646–2669 (2025).

    Google Scholar 

  6. Barbé-Tuana, F., Funchal, G., Schmitz, C. R. R., Maurmann, R. M. & Bauer, M. E. The interplay between immunosenescence and age-related diseases. Semin. Immunopathol. 42, 545–557 (2020).

    Google Scholar 

  7. Franceschi, C. et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann. N. Y. Acad. Sci. 908, 244–254 (2000).

    Google Scholar 

  8. Rodriguez, I. J. et al. Immunosenescence study of T cells: a systematic review. Front. Immunol. 11, 604591 (2021).

    Google Scholar 

  9. Anaya, J. M., Lozada-Martinez, I. D., Torres, I. & Shoenfeld, Y. Autoimmunity in centenarians. A paradox. J. Transl. Autoimmun. 8, 100237 (2024).

    Google Scholar 

  10. Marzo, R. R. et al. Front. Public Health 11, 1193789 (2023).

  11. Ahuja, S. K. et al. Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection. Nat. Commun. 14, 3286 (2023).

    Google Scholar 

  12. Vitlic, A., Lord, J. M. & Phillips, A. C. Stress, ageing and their influence on functional, cellular and molecular aspects of the immune system. Age 36, 9631 (2014).

    Google Scholar 

  13. Lozada-Martinez, I. D., Diazgranados-Garcia, M. C., Castelblanco-Toro, S. & Anaya, J. M. Global research on centenarians: a historical and comprehensive bibliometric analysis from 1887 to 2023. Ann. Geriatr. Med. Res. 28, 144–155 (2024).

    Google Scholar 

  14. Fundación Saldarriaga Concha, Fedesarrollo, PROESA & DANE. Misión Colombia Envejece—Una Investigación Viva. (Bogotá, D.C., Colombia, 2023). https://www.saldarriagaconcha.org/wp-content/uploads/2023/11/MCE-00-1-Completo-Octubre12-2023.pdf.

  15. von Elm, E. et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J. Clin. Epidemiol. 61, 344–349 (2008).

    Google Scholar 

  16. Daunay, A. et al. Centenarians consistently present a younger epigenetic age than their chronological age with four epigenetic clocks based on a small number of CpG sites. Aging (Albany NY) 14, 7718–7733 (2022).

    Google Scholar 

  17. Vacinova, G. et al. Regulated upon activation, normal T cell expressed and secreted (RANTES) levels in the peripheral blood of patients with Alzheimer's disease. Neural Regen. Res. 16, 796–800 (2021).

    Google Scholar 

  18. Guo, Y. et al. Elevated RANTES levels are associated with increased risk of cerebral atherosclerotic stenosis. BMC Neurol. 23, 39 (2023).

    Google Scholar 

  19. Link, H. Current state and future opportunities in granulocyte colony-stimulating factor (G-CSF). Support. Care Cancer 30, 7067–7077 (2022).

    Google Scholar 

  20. Galván, S. T. et al. Plasma concentrations of granulocyte colony-stimulating factor (G-CSF) in patients with substance use disorders and comorbid major depressive disorder. Sci. Rep. 11, 13629 (2021).

    Google Scholar 

  21. Chen, Y. & Rudolph, K. L. Granulocyte colony-stimulating factor acts on lymphoid-biased, short-term hematopoietic stem cells. Haematologica 106, 1516–1518 (2021).

    Google Scholar 

  22. Ju, Z. et al. Telomere dysfunction induces environmental alterations limiting hematopoietic stem cell function and engraftment. Nat. Med. 13, 742–747 (2007).

    Google Scholar 

  23. He, Z. et al. Declining neutrophil production despite increasing G-CSF levels is associated with chronic inflammation in elderly rhesus macaques. J. Leukoc. Biol. 109, 1033–1043 (2021).

    Google Scholar 

  24. Van Avondt, K. et al. Neutrophils in aging and aging-related pathologies. Immunol. Rev. 314, 357–375 (2023).

    Google Scholar 

  25. Alonso-Fernández, P., Puerto, M., Maté, I., Ribera, J. M. & De la Fuente, M. Neutrophils of centenarians show function levels similar to those of young adults. J. Am. Geriatr. Soc. 56, 2244–2251 (2008).

    Google Scholar 

  26. Duchowny, K. A. et al. The aging immune system and all-cause mortality in older Americans: differences across sex and race/ethnicity. Immun. Ageing 22, 25 (2025).

    Google Scholar 

  27. Chang, S. T. et al. Age-dependent immune profile in healthy individuals: an original study, systematic review and meta-analysis. Immun. Ageing 21, 75 (2024).

    Google Scholar 

  28. Evert, J., Lawler, E., Bogan, H. & Perls, T. Morbidity profiles of centenarians: survivors, delayers, and escapers. J. Gerontol. A Biol. Sci. Med. Sci. 58, M232–M237 (2003).

    Google Scholar 

  29. Lozada-Martinez, I. D. et al. Arch. Gerontol. Geriatr. Plus 1, 100006 (2024).

  30. Conte, M. et al. Human aging and longevity are characterized by high levels of mitokines. J. Gerontol. A Biol. Sci. Med. Sci. 74, 600–607 (2019).

    Google Scholar 

  31. Accardi, G. et al. The Phenotypic Characterization of the Oldest Italian Man from December 28, 2020, to September 23, 2021, A.T., strengthens the idea that the immune system can play a key role in the attainment of extreme longevity. J. Clin. Med. 12, 7591 (2023).

    Google Scholar 

  32. Wherry, E. J. & Kurachi, M. Molecular and cellular insights into T cell exhaustion. Nat. Rev. Immunol. 15, 486–499 (2015).

    Google Scholar 

  33. Slaets, H., Veeningen, N., de Keizer, P. L. J., Hellings, N. & Hendrix, S. Are immunosenescent T cells really senescent? Aging Cell 23, e14300 (2024).

    Google Scholar 

  34. Ng, T. P. et al. Socio-Environmental, Lifestyle, Behavioural, and Psychological Determinants of Biological Ageing: The Singapore Longitudinal Ageing Study. Gerontology 66, 603–613 (2020).

    Google Scholar 

  35. Tzemah-Shahar, R., Hochner, H., Iktilat, K. & Agmon, M. What can we learn from physical capacity about biological age? A systematic review. Ageing Res. Rev. 77, 101609 (2022).

    Google Scholar 

  36. Nicita-Mauro, V. et al. Smoking, aging and the centenarians. Exp. Gerontol. 43, 95–101 (2008).

    Google Scholar 

  37. Gao, S., Deng, H., Wen, S. & Wang, Y. Effects of accelerated biological age on depressive symptoms in a causal reasoning framework. J. Affect. Disord. 339, 732–741 (2023).

    Google Scholar 

  38. Zhu, M., Lv, T., Peng, M., Sun, H. & Li, Y. PTP-3 regulated by VB12 is important for ageing health in C. elegans. NPJ Aging 11, 10 (2025).

    Google Scholar 

  39. Elliott, M. L. et al. Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy. Nat. Aging 1, 295–308 (2021).

    Google Scholar 

  40. Balachandran, A. et al. Pace of Aging analysis of healthspan and lifespan in older adults in the US and UK. Nat. Aging 5, 1132–1142 (2025).

    Google Scholar 

  41. Santos-Pujol, E. et al. The multiomics blueprint of the individual with the most extreme lifespan. Cell Rep. Med. 6, 102368 (2025).

    Google Scholar 

  42. Anaya, J. M., Alpi, S. V., Castelblanco-Toro, S. M., Lozada-Mart¡nez, I. D. & Salazar-Uribe, J. C. Quality of life and well-being in Colombian centenarians. Sci. Rep 15, 32071 (2025).

    Google Scholar 

  43. O'bryant, S. E. et al. Staging dementia using Clinical Dementia Rating Scale Sum of Boxes scores: a Texas Alzheimer's research consortium study. Arch. Neurol. 65, 1091–1095 (2008).

    Google Scholar 

  44. Feng, L. et al. Malnutrition is positively associated with cognitive decline in centenarians and oldest-old adults: a cross-sectional study. EClinicalMedicine 47, 101336 (2022).

    Google Scholar 

  45. Cheng, A., Leung, Y., Harrison, F. & Brodaty, H. The prevalence and predictors of anxiety and depression in near-centenarians and centenarians: a systematic review. Int. Psychogeriatr 31, 1539–1558 (2019).

    Google Scholar 

  46. Ruiz, F. J. et al. Validity of the Satisfaction with Life Scale in Colombia and factorial equivalence with Spanish data. Rev. Latinoam Psicol 51, 58–65 (2019).

    Google Scholar 

  47. Ribeiro, O., Teixeira, L., Ara£jo, L., Afonso, R. M. & Pachana, N. Predictors of anxiety in centenarians: health, economic factors, and loneliness. Int. Psychogeriatr 27, 1167–1176 (2015).

    Google Scholar 

  48. Chavarro Carvajal, D. A. et al. Scales frequently used in geriatrics [Escalas de uso frecuente en geriatría] [Internet]. 1st ed. (Pontificia Universidad Javeriana, Bogotá, 2020) [cited 2025 Sep 7]. 1–80 p. https://apidspace.javeriana.edu.co/server/api/core/bitstreams/ec7f3b83-0fc3-48a5-890d-bb6b2a9d10a8/content.

  49. Croize-Pourcelet, C. et al. Geriatric syndromes in a centenarians population. Aging Clin. Exp. Res. 34, 3131–3136 (2022).

    Google Scholar 

  50. Lozada-Martinez, I. D., Vindas-Meza, L., Castelblanco-Toro, S., Salazar-Uribe, J. C. & Anaya, J. M. The impact of nutritional status on centenarians’ physical, mental, and functional health. Clin. Nutr. Open Sci. 60, 10–20 (2025).

    Google Scholar 

  51. Chen, T. Y. et al. Prevalence and correlates of falls among centenarians: results from the Five-Country Oldest Old Project (5-COOP). J. Gerontol. A Biol. Sci. Med. Sci. 75, 974–979 (2020).

    Google Scholar 

  52. Zhong, B.L., Li, H.J., Xu, Y.M. & Jiang, X.F. Front. Public Health 10, 1026034 (2022).

  53. Cress, M. E. et al. Assessing physical performance in centenarians: norms and an extended scale from the Georgia Centenarian Study. Curr. Gerontol. Geriatr. Res. 2010, 1–6 (2010).

    Google Scholar 

  54. Lee, G. C. et al. Immunologic resilience and COVID-19 survival advantage. J. Allergy Clin. Immunol. 148, 1176–1191 (2021).

    Google Scholar 

  55. Levine, M. E. et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY) 10, 573–591 (2018).

    Google Scholar 

  56. Wu, J. et al. Age differences in associations of serum alkaline phosphatase and mortality among peritoneal dialysis patients. Chin. Med. J. 132, 232–236 (2019).

    Google Scholar 

  57. Vieira, F. T. et al. Hip muscle strength, dynamic balance and functional capacity of community-dwelling older adults aged 60 and older: a cross-sectional study. J. Biomech. 129, 110753 (2021).

    Google Scholar 

  58. Lebart, L., Morineau, A., Piron, M. Statistique Exploratoire Multidimensionnelle. (Dunod Paris, 1995).

  59. Acosta-Ampudia, Y. et al. Persistent autoimmune activation and proinflammatory state in post-coronavirus disease 2019 syndrome. J. Infect. Dis. 225, 2155–2162 (2022).

    Google Scholar 

  60. Di Mitri, D. et al. Reversible senescence in human CD4+CD45RA+CD27- memory T cells. J. Immunol. 187, 2093–2100 (2011).

    Google Scholar 

Download references

Acknowledgements

We extend our special thanks to the members of the Colombian Centenarians Alliance who made the design and maintenance of this national study possible. To the University EIA, Soluciones Moleculares SAS, the Office for the Older Persons of the Bogotá Health Secretary, and particularly to the commitment of the centenarians for their desire to contribute to the study, understanding, and promotion of extreme longevity. This work was supported by the Colombian Centenarians Alliance, Clínica de la Costa (Barranquilla, Colombia) and Universidad del Rosario (Bogotá, Colombia).

Author information

Authors and Affiliations

  1. Colombian Centenarians Alliance, Bogotá, Colombia

    Juan-Manuel Anaya, Ivan David Lozada-Martinez, Manuel Rojas, Diana M. Monsalve, Jesús Armando Álvarez-Álvarez, María José Díaz Gutiérrez, Olianis Pájaro, Brenda Guerra, Juan Esteban Gallo, Isaura Torres, Carolina Ramírez-Santana, Andres Angelo Cadena Bonfanti & Yeny Acosta-Ampudia

  2. Universidad de la Costa, Barranquilla, Colombia

    Juan-Manuel Anaya & Ivan David Lozada-Martinez

  3. Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA

    Edward A. Ruiz-Narváez

  4. Center for Autoimmune Diseases Research, School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia

    Manuel Rojas, Diana M. Monsalve, Carolina Ramírez-Santana & Yeny Acosta-Ampudia

  5. Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, CA, USA

    Manuel Rojas

  6. Grupo de Errores Innatos de la Inmunidad, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia

    Jesús Armando Álvarez-Álvarez

  7. Clínica de la Costa, Barranquilla, Colombia

    María José Díaz Gutiérrez, Olianis Pájaro, Brenda Guerra & Andres Angelo Cadena Bonfanti

  8. ASRT Laboratories, ASRT Inc., Birmingham, AL, USA

    Juan Esteban Gallo & Isaura Torres

  9. Universidad EIA, Medellín, Colombia

    Isaura Torres

  10. Universidad Simón Bolívar, Barranquilla, Colombia

    Andres Angelo Cadena Bonfanti

Authors
  1. Juan-Manuel Anaya
    View author publications

    Search author on:PubMed Google Scholar

  2. Edward A. Ruiz-Narváez
    View author publications

    Search author on:PubMed Google Scholar

  3. Ivan David Lozada-Martinez
    View author publications

    Search author on:PubMed Google Scholar

  4. Manuel Rojas
    View author publications

    Search author on:PubMed Google Scholar

  5. Diana M. Monsalve
    View author publications

    Search author on:PubMed Google Scholar

  6. Jesús Armando Álvarez-Álvarez
    View author publications

    Search author on:PubMed Google Scholar

  7. María José Díaz Gutiérrez
    View author publications

    Search author on:PubMed Google Scholar

  8. Olianis Pájaro
    View author publications

    Search author on:PubMed Google Scholar

  9. Brenda Guerra
    View author publications

    Search author on:PubMed Google Scholar

  10. Juan Esteban Gallo
    View author publications

    Search author on:PubMed Google Scholar

  11. Isaura Torres
    View author publications

    Search author on:PubMed Google Scholar

  12. Carolina Ramírez-Santana
    View author publications

    Search author on:PubMed Google Scholar

  13. Andres Angelo Cadena Bonfanti
    View author publications

    Search author on:PubMed Google Scholar

  14. Yeny Acosta-Ampudia
    View author publications

    Search author on:PubMed Google Scholar

Contributions

J.M.A., E.A.R.N., I.D.L.M., and M.R. conceived and designed the study. J.M.A., E.A.R.N., I.D.L.M., M.R., Y.A.A., D.M.M. and J.A.A.A. contributed to methodology and data analysis. J.M.A., I.D.L.M., M.J.D.G., O.P., and B.G. collected and curated the data. J.E.G., I.T. and C.R.S. contributed to biological sample management for formal analysis and interpretation. A.A.C.B. supported clinical and laboratory work. J.M.A., I.D.L.M., and E.A.R.N. wrote the first draft of the paper. All authors contributed to data interpretation and revised the paper for intellectual content. J.M.A. supervised the study. All authors have read and approved the paper.

Corresponding author

Correspondence to Juan-Manuel Anaya.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

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

Supplementary information

Supplementary Information

Supplementary Data 1

Supplementary Data 2

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Anaya, JM., Ruiz-Narváez, E.A., Lozada-Martinez, I.D. et al. Biological age and immunosenescence in Colombian centenarians. npj Aging (2026). https://doi.org/10.1038/s41514-026-00340-6

Download citation

  • Received: 01 October 2025

  • Accepted: 27 January 2026

  • Published: 16 February 2026

  • DOI: https://doi.org/10.1038/s41514-026-00340-6

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Download PDF

Associated content

Collection

Immuno-senescence

Advertisement

Explore content

  • Research articles
  • Reviews & Analysis
  • News & Comment
  • Collections
  • Follow us on X
  • Sign up for alerts
  • RSS feed

About the journal

  • Aims & Scope
  • Journal Information
  • Content types
  • About the Editors
  • Contact
  • Open Access
  • Calls for Papers
  • Article Processing Charges
  • Editorial policies
  • Journal Metrics
  • About the Partner

Publish with us

  • For Authors and Referees
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

npj Aging (npj Aging)

ISSN 2731-6068 (online)

nature.com sitemap

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research