Frailty is a common syndrome in older adults and is characterized by weight loss, low activity, and weakness. Aging and frailty have been linked to poor health outcomes. Frailty has been identified as an outcome of aging in humans. Moreover, it makes older adults more vulnerable to different forms of stress. A hallmark of frailty is a weakened immune system, which lowers the capability of aged people to ward off diseases.
A recent study published in Nature Aging aimed to explore different characteristics of human immune cells in relation to aging. Led by Oscar Junhong Luo, the research team collected cord blood from neonates (an infant aged less than four weeks) and peripheral blood (blood flowing through the heart, capillaries, arteries, and veins) from healthy young adults, non-frail older adults, and frail older adults, with the aim to assess blood samples based on changes in the T-cell antigen receptor (TCR) repertoire and transcriptomics (study of the complete RNA transcript set to understand the structure of genes) at a single-cell level.
Oscar and his team profiled approximately 114,467 immune cells collected from cord and peripheral blood using single-cell RNA and TCR sequencing. The researchers reported on the accumulation of transcriptome variability and heterogeneity in the immune cells, which was dependent on the age of the participants. Moreover, they identified distinguishing transcription factors in the selected cell types of precise age groups.
Previous studies have shed light on chief characteristics of human immune aging, such as a decrease in the TCR repertoire and number of naïve lymphocytes, together with an increase in the number of memory and effector cells with high inflammation response. These memory cells are generally able to identify foreign substances that the immune system has been previously exposed to.
Findings from the trajectory analysis elucidated that cells collected from both frail and non-frail older adults can be often classified into distinctive paths. The T-cell subtypes in old adults shared abundant TCR clonotypes (unique amino acid sequences), which hinted at disparities in pluripotency (the ability of a particular cell to form any of the three primary embryonic germ cell layers and consequently all cells present in an adult) and the resilience of the aged T cells.
The research team identified a subset of frailty-specific monocyte, which was characterized by an absolutely high expression of long noncoding RNAs, namely NEAT1 and MALAT1. This study added evidence to previous research in that it explored characteristics of human immune cells that were specific to frailty, based on the inclusive magnitudes in the immune landscape of frailty and aging. Oscar and collaborators mentioned that this study offered great insights into the detection of a novel cell type, particular cell markers, and comprehensive genomics resources related to immune aging and frailty in humans.
Luo, O.J., Lei, W., Zhu, G. et al. Multidimensional single-cell analysis of human peripheral blood reveals characteristic features of the immune system landscape in aging and frailty. Nat Aging 2, 348–364 (2022). https://doi.org/10.1038/s43587-022-00198-9
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