Inflammaging: Experimental Insights and Translational Advances

Area of Science:

• Gerontology and immunology
• Molecular and cellular biology
• Translational medicine

Background:

• Inflammaging, a persistent low-grade inflammation, is a key factor in age-related diseases like cardiovascular dysfunction and neurodegeneration.
• Understanding the mechanisms of inflammaging is crucial for developing interventions to promote healthy aging.

Purpose of the Study:

• To review recent advances in the mechanistic basis of inflammaging.
• To discuss preclinical and early-phase clinical interventions targeting inflammaging.
• To highlight the potential of precision geroscience for extending healthspan.

Main Methods:

• Review of recent literature on cellular senescence, SASP, mitochondrial dysfunction, immune cell senescence, and nutrient-sensing pathways.
• Analysis of single-cell and spatial transcriptomics data.
• Evaluation of preclinical and clinical trial data for senolytics, senomorphics, metabolic modulators, and immune-based therapies.

Main Results:

• Inflammaging mechanisms include cellular senescence, SASP, mitochondrial dysfunction, and immune dysregulation.
• Tissue-specific patterns of inflammaging revealed by transcriptomics highlight systemic complexity.
• Interventions like senolytics, senomorphics, and metabolic modulators show promise in preclinical and early clinical studies.
• Early clinical trials demonstrate safety and efficacy in frail older adults, with improved physical function and immune response.

Conclusions:

• Inflammaging is a modifiable driver of age-related pathology.
• Personalized, multimodal interventions targeting inflammaging are essential for extending healthspan.
• Further research is needed for biomarker development and addressing population heterogeneity.