Age-Related Oxidative Stress and Mitochondrial Dysfunction in Lymph Node Stromal Cells Limit the Peripheral T Cell...

Area of Science:

• Immunology
• Aging research
• Cell biology

Background:

• Lymph nodes (LN) are crucial for immune responses and maintaining naive lymphocytes.
• Aging impairs LN function, affecting immune responses, but the underlying mechanisms are unclear.
• Age-related degenerative changes in LN stromal cells are known to impact immune function.

Purpose of the Study:

• To investigate the nature of age-related defects in LN stromal cells.
• To determine the role of mitochondrial dysfunction and oxidative stress in aging LNs.
• To assess the potential of antioxidant interventions to restore LN function in aged individuals.

Main Methods:

• Analysis of mitochondrial function (ROS, potential, mass) in isolated LN stromal cells (FRC, LEC, BEC) from young and old mice.
• In vitro assessment of LN stromal cell support for T cell survival.
• In vivo administration of antioxidants (NAC, mitoquinone, urolithin A) to aged mice.
• Evaluation of antigen-specific CD8+ T cell responses post-vaccination in aged mice treated with NAC.

Main Results:

• Aging leads to increased mitochondrial ROS, reduced mitochondrial potential, and increased mitochondrial mass in all major LN stromal cell subsets.
• Old LN stromal cells show impaired T cell survival support in vitro, which is rescued by antioxidants.
• Mitochondrial dysfunction in FRCs is observed in vivo during infection or vaccination.
• In vivo NAC treatment in aged mice restored CD8+ T cell numbers and granzyme B production to levels seen in young adults.

Conclusions:

• Age-related lymph node stromal cell dysfunction is characterized by mitochondrial dysfunction and oxidative stress.
• Targeting mitochondrial dysfunction and oxidative stress with antioxidants can restore immune responses in aged individuals.
• These findings suggest a promising therapeutic strategy for enhancing immunity in the elderly.