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Cellular polarity in aging: role of redox regulation and nutrition

Significance Statement

– Senescence-related functional losses emanate mainly from the derangement of the cellular redox state.

– Primary cilium- alterations on cilia assembly and/or function due to deregulation of redox status may affect tissues homeostasis and contribute to senescence. Polarity-dependent processes are altered during aging.

– Redox deregulation of the LKB1/AMPK signaling axis may impair the integration of metabolic and cellular information to regulate cellular polarity. This may involve cross-talks between cytoskeleton and extracellular matrix.

– Phytochemicals regulate the LKB1/AMPK signaling axis and elicit an antioxidant response, mediated by Nrf2.

– The gastrointestinal epithelium is a preferred target for phytochemicals bioactivity.

– The hypothesis that redox deregulation of cellular polarity is a central process during aging can be used as a guide for nutritional interventions.


Cellular polarity in aging: role of redox regulation and nutrition-Global Medical Discovery












Journal Reference

Soares H, Marinho HS, Real C, Antunes F.

Genes Nutr. 2014 Jan;9(1):371.

Departamento de Química e Bioquímica, Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal.


Cellular polarity concerns the spatial asymmetric organization of cellular components and structures. Such organization is important not only for biological behavior at the individual cell level, but also for the 3D organization of tissues and organs in living organisms. Processes like cell migration and motility, asymmetric inheritance, and spatial organization of daughter cells in tissues are all dependent of cell polarity. Many of these processes are compromised during aging and cellular senescence. For example, permeability epithelium barriers are leakier during aging; elderly people have impaired vascular function and increased frequency of cancer, and asymmetrical inheritance is compromised in senescent cells, including stem cells. Here, we review the cellular regulation of polarity, as well as the signaling mechanisms and respective redox regulation of the pathways involved in defining cellular polarity. Emphasis will be put on the role of cytoskeleton and the AMP-activated protein kinase pathway. We also discuss how nutrients can affect polarity-dependent processes, both by direct exposure of the gastrointestinal epithelium to nutrients and by indirect effects elicited by the metabolism of nutrients, such as activation of antioxidant response and phase-II detoxification enzymes through the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In summary, cellular polarity emerges as a key process whose redox deregulation is hypothesized to have a central role in aging and cellular senescence.


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