The Mitochondrial Clock: Biogenesis, Dynamics, and Quality Control in Human Aging

Mitochondrial biology has gained prominence as a core focus within aging research, driven by advances that underscore mitochondria’s pivotal role in regulating cellular health, metabolism, and longevity. In recent years, studies have increasingly revealed that mitochondrial biogenesis, dynamics (including fusion and fission processes), and quality control systems such as mitophagy and proteostasis are intimately linked to the progression of human aging and its associated pathologies. Persistent alterations in these mitochondrial processes have been connected with hallmark traits of aging cells, such as diminished oxidative phosphorylation, increased generation of reactive oxygen species, and compromised mitochondrial DNA integrity. Despite these insights, critical gaps persist regarding whether these changes are primary drivers of systemic aging, mere contributors to age-related cellular stress, or both. Particularly, unresolved questions remain about the temporal sequence of such alterations, their tissue specificity, and the existence of a measurable “mitochondrial age” that could serve as a reliable biomarker of aging and disease risk.

This Research Topic aims to unravel the intricate interplay of mitochondrial biogenesis, network dynamics, and quality control mechanisms throughout the human lifespan. The principal objective is to clarify how the regulation and breakdown of mitochondrial homeostasis contribute to functional decline and to explore the hypothesis that mitochondria operate as a molecular “clock” governing aging trajectories. Key questions include: How do core regulators of mitochondrial generation and network remodeling shift with age and in disease? What roles do altered fusion–fission dynamics play in propagating mitochondrial DNA mutations and tissue-specific pathologies? Can changes in mitophagy efficiency and proteostasis be used to predict or forestall age-associated dysfunction, and which interventions can effectively reset or delay the mitochondrial clock in humans? Through integrating molecular, cellular, and translational investigations, this topic aspires to uncover foundational mechanisms and actionable intervention points that enhance healthspan.

This Research Topic will focus on the investigation of mitochondrial function in the context of human aging, with an emphasis on mechanisms, biomarkers, and interventions. It will primarily examine changes occurring over the adult lifespan, while excluding unrelated topics such as non-mitochondrial organelle aging or studies lacking translational relevance. To gather further insights in mitochondrial involvement in aging and therapeutics, we welcome articles addressing, but not limited to, the following themes:

o Regulation of mitochondrial biogenesis across the lifespan and in age-associated diseases
o Alterations in mitochondrial network dynamics and their effects on tissue-specific aging
o Mechanistic insights into mitophagy and mitochondrial proteostasis during aging
o Development of biomarkers and “mitochondrial age” metrics for translational research
o Nutritional, pharmacological, genetic, and lifestyle interventions targeting mitochondrial health or rejuvenation
o Application of multi-omics, advanced imaging, and human cohort studies to dissect mitochondrial aging
o Comparative studies using human cell models, organoids, and animal systems to validate findings
o Novel therapeutic approaches and their outcomes on mitigating mitochondrial dysfunction in aging

If submitting, you may share original research, reviews, methodological papers, perspectives, or clinical studies relevant to the above themes.

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
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• ... 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
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Mitochondrial Biogenesis, Mitochondrial Dynamics, Mitophagy, Mitochondrial Proteostasis, Oxidative Phosporylation Decline, Reactive Oxygen Species (ROS), Mitochondrial DNA Integrity, Mitochondrial Aging Biomarkers, Mitochondrial Clock of Aging

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.