Production of MHCII-expressing classical monocytes increases during aging in mice and humans
Pijus K Barman1,2, Juliana E Shin1,2, Sloan A Lewis3,4
1Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Abstract:
Aging is associated with increased monocyte production and altered monocyte function. Classical monocytes are heterogenous and a shift in their subset composition may underlie some of their apparent functional changes during aging. We have previously shown that mouse granulocyte-monocyte progenitors (GMPs) produce "neutrophil-like" monocytes (NeuMo), whereas monocyte-dendritic cell progenitors (MDPs) produce monocyte-derived dendritic cell (moDC)-producing monocytes (DCMo). Here, we demonstrate that classical monocytes from the bone marrow of old male and female mice have higher expression of DCMo signature genes (H2-Aa, H2-Ab1, H2-Eb1, Cd74), and that more classical monocytes express MHCII and CD74 protein. Moreover, we show that bone marrow MDPs and classical monocytes from old mice yield more moDC. We also demonstrate higher expression of Aw112010 in old monocytes and that Aw112010 lncRNA activity regulates MHCII induction in macrophages, which suggests that elevated Aw112010 levels may underlie increased MHCII expression during monocyte aging. Finally, we show that classical monocyte expression of MHCII is also elevated during healthy aging in humans. Thus, aging-associated changes in monocyte production may underlie altered monocyte function and have implications for aging-associated disorders.
Insights
Aging alters monocyte subsets, increasing a type that produces more dendritic cells. This shift, linked to specific gene expression and lncRNA activity, is observed in both mice and humans, potentially impacting age-related diseases.
Area of Science:
- Immunology
- Aging research
- Cell biology
Background:
- Aging is linked to increased monocyte production and functional changes.
- Classical monocytes are heterogeneous, with subset shifts potentially explaining functional alterations in aging.
- Previous work identified distinct monocyte subsets derived from granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs).
Purpose of the Study:
- To investigate changes in classical monocyte subset composition during aging.
- To determine the functional implications of these changes on dendritic cell production.
- To explore the role of specific genes and lncRNAs in age-related monocyte alterations.
Main Methods:
- Analysis of classical monocyte gene expression (H2-Aa, H2-Ab1, H2-Eb1, Cd74) in young vs. old mice.
- Assessment of MHCII and CD74 protein expression on monocytes.
- Evaluation of dendritic cell yield from bone marrow progenitors and monocytes.
- Measurement of Aw112010 long non-coding RNA (lncRNA) expression and its regulatory role in macrophages.
- Comparison of MHCII expression in human classical monocytes from young and old individuals.
Main Results:
- Old mice exhibit higher expression of dendritic cell-producing monocyte (DCMo) signature genes and proteins (MHCII, CD74) in classical monocytes.
- Bone marrow MDPs and classical monocytes from old mice produce more monocyte-derived dendritic cells (moDCs).
- Elevated Aw112010 lncRNA levels in old monocytes correlate with increased MHCII expression, suggesting a regulatory role.
- Increased classical monocyte MHCII expression is also observed in healthy aging humans.
Conclusions:
- Aging skews monocyte production towards a subset with enhanced dendritic cell-generating capacity.
- Increased expression of specific genes and the lncRNA Aw112010 contributes to altered monocyte function during aging.
- These age-associated monocyte changes in mice and humans may have significant implications for aging-related disorders.
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