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PreprintCited by 1Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsSingle-cell and spatial transcriptomics

Circulating Cell Type Senescence Signatures Reveal High-Resolution Health Status and Trajectories in Human Longitudinal Studies

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Olinger, Bradley, Anerillas, Carlos, Herman, Allison B., Tsitsipatis, Dimitrios, Banarjee, Reema, Tanaka, Toshiko, Candia, Julian, Maragkakis, Manolis +7 more·2026·medRxiv
DOI 10.64898/2026.02.06.26345739PMC PMC12919141
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Abstract

SUMMARY: Cellular senescence increases in frequency with age and is implicated in age-related pathologies, and identifying circulating biomarkers of senescence holds great diagnostic potential. Circulating senescence signatures are predictive of many age-related traits and diseases, though cell type-specific senescence signatures have not been comprehensively explored. In this study, senescence signatures from the Senescence Catalog (SenCat), including 14 human cell types such as peripheral blood mononuclear cells, renal epithelial cells, vascular smooth muscle cells, among others, are examined for their clinical relevance in circulation in two longitudinal studies: 1,275 participants of the Baltimore Longitudinal Study of Aging (BLSA) and 997 participants of the Invecchiare in Chianti (InCHIANTI) study. Notably, pooled senescence proteins outperformed non-senescence proteins in predicting many clinical parameters such as age and hypertension, and in many instances cell type senescence signatures mapped most strongly to their corresponding health domain. Importantly, the immune cell senescence signature is associated with future onset of several diseases such as diabetes. This study demonstrates that circulating cell type-specific biomarkers of senescence can reveal higher resolution health status than previously attained. HIGHLIGHTS: Circulating senescence associated proteins tend to outperform non-senescence proteins as biomarkers of clinical phenotypes in two independent longitudinal studies. A core senescence signature developed from 14 human cell types predicted a range of clinical phenotypes during aging. Cell type senescence signatures more strongly associated with their corresponding health domains. The immune cell senescence signature and others were associated with mortality and diabetes onset, highlighting relevance for assessing health trajectories.

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  • The companion study shows that SenCat's protein component can identify clinically relevant senotype-specific signatures in human plasma proteomic data, with better performance and tissue resolution than earlier reports.

    “our companion study19 demonstrates that the proteomic component of SenCat can be leveraged to identify clinically relevant senotype-specific signatures in human plasma proteomic data, with greater performance and tissue-resolution than previously reported.”

    From SenCat: Cataloging human cell senescence through multi-omic profiling of multiple senescent primary cell types (2026) · cites this paper as [19]

    The Results describe clinically relevant cell type-specific signatures derived from SenCat proteins and measured in human plasma; the Discussion says they offer higher-resolution insights into health status than previously achieved. The reported performance advantage is over non-senescence proteins in predicting clinical traits, not over earlier reports. The copy therefore does not support the claim of better performance than previously reported. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • A companion study connected blood markers of specific senotypes to particular age-related conditions.

    “We have validated its usefulness in a companion study that linked senotype-specific senescence markers in blood to specific age-associated conditions.19”

    From SenCat: Cataloging human cell senescence through multi-omic profiling of multiple senescent primary cell types (2026) · cites this paper as [19]

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Authors
Olinger, B., Anerillas, C., Herman, A. B., Tsitsipatis, D., Banarjee, R., Tanaka, T., Candia, J., Maragkakis, M., Bandinelli, S., Walker, K. A., Simonsick, E. M., Qi, Y. A., Ferrucci, L., Gorospe, M., & Basisty, N.
Affiliations
  • Johns Hopkins University (US)
  • Consejo Superior de Investigaciones Científicas (ES)
  • National Institute on Aging (US)
  • Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, Maryland, USA
  • National Institutes of Health (US)
  • Geriatric Unit, Azienda Sanitaria toscana centro, Firenze, Italy
Corresponding author
Basisty, Nathan
ORCID
Venue
medRxiv
Publisher
openRxiv
Published
2026-02-09
DOI
10.64898/2026.02.06.26345739
PMC
PMC12919141
OpenAlex
W7128438450
Cited by
0
References
11
Type
posted content
Language
en
Open access
Licence
Locations
  • medRxiv (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
Funders
  • U.S. Department of Health and Human Services
  • National Institutes of Health (NIA U54 AG079779)
  • National Institute on Aging (U54AG079779)
  • Common Fund
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
Keywords
cellular senescence, aging, health trajectories, hypertension, diabetes onset, mortality, peripheral blood mononuclear cells, vascular smooth muscle cells, renal epithelial cells, Baltimore Longitudinal Study of Aging

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