Autophagy, Mitophagy, and Proteostasis in Aging and Metabolic Decline

Aging is characterized by the progressive deterioration of cellular quality control mechanisms that are essential for maintaining homeostasis. Among these, autophagy, mitophagy, and proteostasis play central roles in clearing damaged macromolecules, recycling cellular components, and preserving organelle integrity. As organisms age, the coordinated activity of these pathways declines, contributing to the accumulation of dysfunctional mitochondria, misfolded proteins, and oxidative damage - hallmarks that are closely intertwined with metabolic dysfunction.

Autophagy serves as a primary recycling system, enabling cells to degrade and repurpose cytoplasmic material under conditions of stress or nutrient deprivation. Mitophagy, a selective form of autophagy targeting damaged mitochondria, is critical for sustaining mitochondrial quality and bioenergetic efficiency. When mitophagy is impaired, defective mitochondria accumulate, driving elevated reactive oxygen species (ROS) production and inflammatory signaling. Proteostasis networks - encompassing the ubiquitin-proteasome system, molecular chaperones, and the unfolded protein response - work in parallel to prevent the toxic aggregation of misfolded proteins. Together, these systems form an integrated surveillance infrastructure that is indispensable for metabolic health.

The dysregulation of these pathways in aging tissues has been implicated in the pathogenesis of a spectrum of metabolic disorders, including type 2 diabetes, obesity-related comorbidities, non-alcoholic fatty liver disease, and sarcopenia. Understanding how these mechanisms fail with age, and how they interact with nutrient sensing pathways such as mTOR, AMPK, and sirtuins, is essential for identifying novel therapeutic targets that could extend healthspan.

This Research Topic invites original research, reviews, and perspectives that explore the molecular, cellular, and systemic dimensions of autophagy, mitophagy, and proteostasis in the context of aging and metabolic decline. Topics of interest include, but are not limited to:

• Age-related impairments in autophagic flux and their metabolic consequences
• Mitophagy regulation and mitochondrial quality control in aging tissues
• Proteostasis network dysfunction and protein aggregation in metabolic disease
• Crosstalk between autophagy, redox signaling, and inflammation
• Caloric restriction, fasting, and exercise as modulators of these pathways
• Preclinical and translational studies targeting autophagy or proteostasis for therapeutic benefit

By bringing together multidisciplinary perspectives from cell biology, genomics, geroscience, and metabolism research, this Research Topic aims to advance our understanding of how cellular quality control underpins healthy aging - and where it breaks down in disease.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Autophagy, Mitophagy, Proteostasis, Metabolic aging, Mitochondrial quality control

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.