Male Monocyte-Like Cells are Prone to a Senescence-Induced Pro-inflammatory State

Area of Science:

• Immunology
• Cell Biology
• Gerontology

Background:

• Chronic systemic inflammation is a hallmark of aging, linked to age-related diseases and senescent immune cells.
• While sex differences in aging are known, the impact of cellular sex on immune cell senescence is not well understood.

Purpose of the Study:

• To investigate the impact of cellular sex on D-galactose-induced immune cell senescence.
• To compare the molecular and inflammatory responses of male and female monocyte-like cells during senescence.

Main Methods:

• Senescence was induced in human male (THP-1) and female (HL-60) monocyte-like cells using D-galactose.
• Evaluated senescence markers, metabolic sensors (Sirt1, pAMPK), mitochondrial function, reactive oxygen species (ROS), and pro-inflammatory markers.

Main Results:

• D-galactose induced senescence markers and senescence-associated secretory phenotype factors (IL-6, VEGF, TGF-β, MMP-9) in both male and female cells.
• Both cell types showed reduced Sirt1/pAMPK, increased mitochondrial ROS, and elevated mitochondrial gene expression.
• Male monocytes exhibited a significantly greater elevation in pro-inflammatory markers (NF-κB, TNF-α, IL-1β, HLA-DR, MCP-1) compared to female cells.

Conclusions:

• Male immune cells are more susceptible to developing a pro-inflammatory state during senescence.
• Findings suggest potential sex-specific differences in immune aging and highlight the need for tailored anti-inflammatory therapies.