Hallmarks of T cell aging

Area of Science:

• Immunology
• Gerontology
• Cellular Biology

Background:

• The aged adaptive immune system exhibits progressive dysfunction, leading to increased autoimmunity, susceptibility to infections and cancer, and reduced vaccine efficacy.
• CD4+ T cell intrinsic alterations contribute to chronic inflammation and accelerate organism-wide aging, highlighting the central role of T cell aging in systemic deterioration.

Purpose of the Study:

• To propose ten molecular hallmarks that represent common denominators of T cell aging.
• To group these hallmarks into primary and secondary categories and explain their role in immunodeficiency and inflammaging.
• To identify molecular targets for interventions aimed at mitigating the aging process.

Main Methods:

• This review synthesizes recent evidence on T cell aging.
• It proposes a framework of ten molecular hallmarks, categorized into primary and secondary.
• It discusses the integrative hallmarks of immunodeficiency and inflammaging.

Main Results:

• Ten molecular hallmarks of T cell aging are proposed: thymic involution, mitochondrial dysfunction, genetic/epigenetic alterations, loss of proteostasis (primary), and reduced TCR repertoire, naive-memory imbalance, T cell senescence, lack of effector plasticity (secondary).
• These hallmarks collectively explain immunodeficiency and inflammaging in aged individuals.
• The relative impact and interconnections of these hallmarks require further investigation.

Conclusions:

• T cell aging is a significant driver of age-related immune decline and systemic deterioration.
• Understanding the molecular hallmarks of T cell aging is critical for developing interventions.
• Further research is needed to elucidate the interplay of these hallmarks and identify therapeutic targets.