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Age-related decrease in TCR repertoire diversity measured with deep and normalized sequence profiling.

Olga V Britanova1, Ekaterina V Putintseva, Mikhail Shugay

  • 1Shemiakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, 117997 Moscow, Russia;

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|February 11, 2014
PubMed
Summary
This summary is machine-generated.

T-cell receptor (TCR) diversity declines with age, impacting immune function. This study reveals a linear decrease in TCR diversity and naive T cells, with unique findings in the oldest individuals suggesting longevity associations.

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Area of Science:

  • Immunology
  • Gerontology
  • Genomics

Background:

  • T-cell receptor (TCR) diversity is crucial for adaptive immunity.
  • The impact of aging on TCR diversity has not been directly quantified.
  • Understanding age-related immune changes is vital for healthspan research.

Purpose of the Study:

  • To directly measure and quantify the decrease in TCR beta diversity with age.
  • To investigate the relationship between TCR diversity, naive T cell percentage, and age.
  • To explore immune profiles associated with longevity.

Main Methods:

  • Utilized high-throughput Illumina sequencing and unique cDNA molecular identifier technology for deep TCR beta repertoire profiling.
  • Analyzed samples from 39 healthy donors across a wide age range (6-90 years).
  • Correlated TCR diversity and naive T cell percentages with donor age.

Main Results:

  • TCR beta diversity per 10^6 T cells showed a significant linear decrease with age, evident by age 40.
  • The percentage of naive T cells strongly correlated with TCR diversity and decreased linearly up to age 70.
  • The oldest individuals (average age 82) exhibited increased TCR diversity, higher naive CD4+ T cells, and fewer expanded clones compared to younger elderly individuals (average age 62).
  • A public TCR beta clonotype set (>10,000) showed decreased abundance with aging, correlating with reduced TCR diversity.

Conclusions:

  • TCR diversity and naive T cell populations decline linearly with age, impacting immune function.
  • Longevity may be associated with specific immune profiles, including preserved TCR diversity and naive T cell subsets.
  • Public TCR clonotypes may serve as biomarkers for immune aging and diversity.