GDF15/MIC-1: a stress-induced immunosuppressive factor which promotes the aging process

Area of Science:

• Immunology
• Gerontology
• Cell Biology

Background:

• Growth differentiation factor 15 (GDF15) is a stress-induced protein regulating immune responses.
• GDF15 levels increase with age, linked to inflammaging and cellular senescence (senescence-associated secretory phenotype - SASP).
• Diverse age-related stresses, including oxidative and metabolic stress, induce GDF15 expression.

Purpose of the Study:

• To investigate the dual role of GDF15 signaling in inflammation and aging.
• To elucidate the mechanisms by which GDF15 influences immune suppression and age-related pathologies.

Main Methods:

• Review of existing literature on GDF15 function in stress, inflammation, and aging.
• Analysis of GDF15 signaling pathways, including TGF-β superfamily and GFRAL/HPA/glucocorticoid pathways.
• Examination of GDF15's impact on immune cells like myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and M2 macrophages.

Main Results:

• GDF15 exhibits anti-inflammatory properties but also acts as a pro-aging factor.
• GDF15 enhances immunosuppression in chronic inflammation by activating MDSCs, Tregs, and M2 macrophages.
• GDF15 signaling contributes to detrimental effects in aged tissues, such as fibrosis and sarcopenia.

Conclusions:

• While GDF15 can mitigate acute inflammation, its persistent signaling in aging promotes immunosuppression and age-related diseases.
• GDF15's survival functions are dysregulated in chronic inflammation, driving aging processes.
• Targeting GDF15 pathways may offer therapeutic strategies for age-related conditions.