The FEBS journalOct 13, 2026

Specific cell cleaning processes in aging and brain diseases: New roles for mitochondrial and nuclear removal

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Oct 14, 2026

Abstract

Aging may lead to increased disease risk due to the accumulation of cellular damage.

Aging is influenced by both genetic and non-genetic factors that contribute to cellular damage.
The ability to manage stress is crucial for longevity and is linked to specific molecular pathways.
Mitophagy and nucleophagy are important processes that help maintain the health of mitochondria and nuclear materials, respectively.
These autophagic processes are essential for the survival of long-lived neurons and help prevent neurodegeneration.
Disruptions in autophagy pathways could play a role in aging and the development of neurodegenerative diseases.
Future research may explore the potential connections between mitophagy and nucleophagy.

Simplified

Ageing is characterized by the progressive accumulation of molecular and cellular damage, driven by both genetic and nongenetic factors and ultimately leading to functional decline and an increased risk of disease. Convergent evidence indicates that many of the mechanisms influencing ageing are intimately related to the ability of the organism to cope with intrinsic and extrinsic stress. Key determinants of this capacity are the molecular pathways that coordinate stress responses throughout life. Among these, general and cargo-specific autophagy have emerged as integral components of cellular and systemic adaptation to stress. Here, we focus on mitophagy, a selective form of autophagy targeting mitochondria, and nucleophagy, the selective autophagic recycling of nuclear material. These processes help safeguard the integrity of two organelles that are central to long-term cellular survival and function. Such homeostatic mechanisms are vital in long-lived neurons, where they mediate damage removal during ageing to protect against neurodegeneration. We further discuss how perturbations in these autophagic pathways may contribute to ageing and neurodegenerative disorders. Finally, we outline key open questions and future challenges in the field, including the largely unexplored possibility of functional connections between mitophagy and nucleophagy, which we identify as an important direction for future research.

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Specific cell cleaning processes in aging and brain diseases: New roles for mitochondrial and nuclear removal

Abstract

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