Nucleophagy delays aging and preserves germline immortality.

Marked alterations in nuclear ultrastructure are a universal hallmark of aging, progeroid syndromes and other age-related pathologies. Here we show that autophagy of nuclear proteins is an important determinant of fertility and aging. Impairment of nucleophagy diminishes stress resistance, germline immortality and longevity.

The complex interplay between autophagy and cell death pathways.

Autophagy is a universal cellular homeostatic process, required for the clearance of dysfunctional macromolecules or organelles. This self-digestion mechanism modulates cell survival, either directly by targeting cell death players, or indirectly by maintaining cellular balance and bioenergetics. Nevertheless, under acute or accumulated stress, autophagy can also contribute to promote different modes of cell death, either through highly regulated signalling events, or in a more uncontrolled inflammatory manner.

Selective Autophagy as a Potential Therapeutic Target in Age-Associated Pathologies.

Progressive accumulation of damaged cellular constituents contributes to age-related diseases. Autophagy is the main catabolic process, which recycles cellular material in a multitude of tissues and organs. Autophagy is activated upon nutrient deprivation, and oncogenic, heat or oxidative stress-induced stimuli to selectively degrade cell constituents and compartments.

Assessment of de novo Protein Synthesis Rates in Caenorhabditis elegans.

Maintaining a healthy proteome is essential for cell and organismal homeostasis. Perturbation of the balance between protein translational control and degradation instigates a multitude of age-related diseases. Decline of proteostasis quality control mechanisms is a hallmark of ageing.

Nucleophagy mediators and mechanisms.

Nuclear recycling is essential for cell and organismal homeostasis. Nuclear architecture perturbations, such as nuclear loss or nuclear enlargement, have been observed in several pathological conditions. Apart from proteasomal components which reside in the nucleus, specific autophagic proteins also shuttle between the nucleus and the cytoplasm.

Crosstalk between Endo/Exocytosis and Autophagy in Health and Disease.

Imbalance between the main intracellular degradative, trafficking and intercellular shuttling pathways has been implicated in disease pathogenesis. Autophagy controls degradation of cellular components, while vesicular trafficking permits transport of material in and out of the cell. Emerging evidence has uncovered the extensive interconnectivity between these pathways, which is crucial to maintain organismal homeostasis.

Nucleophagy: from homeostasis to disease.

Nuclear abnormalities are prominent in degenerative disease and progeria syndromes. Selective autophagy of organelles is instrumental in maintaining cell homeostasis and prevention of premature ageing. Although the nucleus is the control centre of the cell by safeguarding our genetic material and controlling gene expression, little is known in relation to nuclear autophagy.

Autophagy and the endo/exosomal pathways in health and disease.

Cell homeostasis requires the concerted action of cellular pathways involved in degradation, trafficking and intercellular communication, which are interlinked to satisfy the cell's needs upon demand. Defects in these pathways instigate the development of several age-related pathologies, such as neurodegenerative and chronic inflammatory diseases. Autophagy is an evolutionarily conserved and tightly regulated process of degrading cellular constituents.

Protein synthesis as an integral quality control mechanism during ageing.

Ageing is manifested as functional and structural deterioration that affects cell and tissue physiology. mRNA translation is a central cellular process, supplying cells with newly synthesized proteins. Accumulating evidence suggests that alterations in protein synthesis are not merely a corollary but rather a critical factor for the progression of ageing.