Polyphenols and Diets as Current and Potential Nutrition Senotherapeutics in Alzheimer’s Disease: Findings from Clinical Trials

Issue title: Therapeutic Trials in Alzheimer’s Disease: Where Are We Now?

Guest editors: Paula I. Moreira, Jesus Avila, Daniela Galimberti, Miguel A. Pappolla, Germán Plascencia-Villa, Aaron A. Sorensen, Xiongwei Zhu and George Perry

Article type: Review Article

Authors: Chen, Xi^{a; b; *} | Walton, Karen^a | Brodaty, Henry^{b; 1} | Chalton, Karen^{a; 1}

Affiliations: [a] School of Medical, Indigenous and Health Sciences, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, Australia | [b] Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Kensington, NSW, Australia

Correspondence: [*] Correspondence to: Dr Xi Sophie Chen, School of Medical, Indigenous and Health Sciences, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia. E-mail: [email protected].

Note: [1] Equal senior authors.

Abstract: Cellular senescence, a hallmark of aging, plays an important role in age-related conditions among older adults. Targeting senescent cells and its phenotype may provide a promising strategy to delay the onset or progression of Alzheimer’s disease (AD). In this review article, we investigated efficacy and safety of nutrition senotherapy in AD, with a focus on the role of polyphenols as current and potential nutrition senotherapeutic agents, as well as relevant dietary patterns. Promising results with neuroprotective effects of senotherapeutic agents such as quercetin, resveratrol, Epigallocatechin-gallate, curcumin and fisetin were reported from preclinical studies. However, in-human trials remain limited, and findings were inconclusive. In future, nutrition senotherapeutic agents should be studied both individually and within dietary patterns, through the perspective of cellular senescence and AD. Further studies are warranted to investigate bioavailability, dosing regimen, long term effects of nutrition senotherapy and provide better understanding of the underlying mechanisms. Collaboration between researchers needs to be established, and methodological limitations of current studies should be addressed.

Keywords: Alzheimer’s disease, cellular senescence, cognition, mild cognitive impairment, nutrition senotherapeutics, senolytic agent

DOI: 10.3233/JAD-231222

Journal: Journal of Alzheimer's Disease, vol. 101, no. s1, pp. S479-S501, 2024