Monitoring Autophagy in Human Aging: Key Cell Models and Insights

Autophagy, a key cellular degradation and recycling pathway, is critical for maintaining cellular homeostasis and responding to metabolic and environmental stress. Evidence for age-related autophagic dysfunction and its implications in chronic age-related diseases including neurodegeneration is accumulating. However, as a complex, multi-step process, autophagy can be challenging to measure, particularly in humans and human aging- and disease-relevant models. This review describes the links between macroautophagy, aging, and chronic age-related diseases. We present three novel human cell models, peripheral blood mononuclear cells (PBMCs), primary dermal fibroblasts (PDFs), and induced neurons (iNs), which serve as essential tools for studying autophagy flux and assessing its potential as a biomarker for aging. Unlike traditional models, these cell models retain age- and disease-associated molecular signatures, enhancing their relevance for human studies. The development of robust tools and methodologies for measuring autophagy flux in human cell models holds promise for advancing our understanding of autophagy's role in aging and age-related diseases, ultimately facilitating the discovery of therapies to enhance health outcomes.