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Senescence in human peripheral blood - A narrative review

L. Ghuan (1), C. Tuttle (1) and A. Maier (1, 2)

  1. @AgeMelbourne, Department of Medicine and Aged Care, University of Melbourne, Melbourne, Victoria, Australia

  2. @AgeAmsterdam, Department of Human Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, The Netherlands

Background

Cellular senescence has been associated with chronological age, biological age and age-related diseases. We have shown that senescent cells accumulate at sites of pathology however; how this influences the senescence levels in blood is unknown. As such the aim of this review was to collate all current evidence investigating senescence in human blood cells and determine how senescence levels are measured within human blood samples and, the association of senescence levels in blood with clinical parameters.


Methods

The PubMed database were searched from inception until 24th April 2019, key search terms focused on senescence (e.g. p16Ink4a) pathways and immunosenescence (e.g. CD28). Additional studies were isolated via analysis of the reference list of included articles (snowballing). Studies using an in vitro design were excluded from this review.


Results

Most of the ‘senescence’ literature in blood focuses on shortened telomere length. Of the remaining studies; immunosenescence (immunodifferentiation) is the most investigated measure of senescence within human blood samples. However; within the last 5 years the cyclin dependent kinase inhibitors (p16Ink4a, p21, p53) are becoming increasingly utilized by researchers to detect levels of senescence in blood. Overall articles that investigated senescence levels in ‘disease’ populations have shown that senescence markers are higher in human blood samples within these populations irrespective of the technique (e.g. qPCR vs. flow cytometry) used to measure senescence. However; the senescence phenotype i.e. p16 pos vs. p53 pos may differ depending on the pathology of the blood sample.


Conclusion

Senescence levels can be measured in human blood samples and is associated with disease phenotypes however; the senescence phenotype of the blood may differ depending on the disease pathology of the population investigated. Furthermore, heterogenous cell populations obscure the ability to identify cell-specific senescence and should be avoided.