Abstract
Organismal ageing is associated with increased chance of morbidity or mortality and it is driven by diverse molecular pathways that are affected by both environmental and genetic factors. The progression of ageing correlates with the gradual accumulation of stressors and damaged biomolecules due to the time-dependent decline of stress resistance and functional capacity, which eventually compromise cellular homeodynamics. As protein machines carry out the majority of cellular functions, proteome quality control is critical for cellular functionality and is carried out through the curating activity of the proteostasis network (PN). Key components of the PN are the two main degradation machineries, namely the ubiquitin-proteasome and autophagy-lysosome pathways along with several stress-responsive pathways, such as that of nuclear factor erythroid 2-related factor 2 (Nrf2), which mobilises cytoprotective genomic responses against oxidative and/or xenobiotic damage. Reportedly, genetic or dietary interventions that activate components of the PN delay ageing in evolutionarily diverse organisms. Natural products (extracts or pure compounds) represent an extraordinary inventory of highly diverse structural scaffolds that offer promising activities towards meeting the challenge of increasing healthspan and/or delaying ageing (e.g., spermidine, quercetin or sulforaphane). Herein, we review those natural compounds that have been found to activate proteostatic and/or anti-stress cellular responses and hence have the potential to delay cellular senescence and/or in vivo ageing.
Highlights
The viability of metazoans largely depends on their ability to regulate metabolic processes in order to generate biomolecules [1]
The protein synthesis module along with the machineries involved in sorting and trafficking of newly synthesised polypeptides are key components of the proteostasis network (PN) and they are complemented by the unfolded protein response of the endoplasmic reticulum (ER) (UPRER ) and mitochondria (UPRmt ), the intra- and extra-cellular molecular chaperones and a number of compartmentalised proteases, along with the two main degradation branches, i.e., the ubiquitin-proteasome system (UPS) and the autophagy-lysosome (ALP)
The catalytic activity of the proteasome is central to quality control of protein synthesis as non-functional newly synthesised polypeptides originating from cytosolic or ER-bound ribosomes are targeted for degradation to cytosolic or ER-bound proteasomes [ER associated protein degradation (ERAD)] respectively [32]
Summary
The viability of metazoans largely depends on their ability to regulate metabolic processes in order to generate biomolecules [1] In eukaryotic cells these molecules are produced in mitochondria through the action of a protein machinery that drives the oxidative phosphorylation (OXPHOS) [2]. Free radicals and their derivatives are highly reactive molecules and, in physiological concentrations, are essential for proper intracellular signalling, metabolism and responses to pathogens If their concentration exceeds the cellular antioxidant capacity, they cause oxidative stress and damage to all cellular biomolecules [4]. Cellular functions deteriorate and compromise these mechanisms, resulting in the impairment of signalling, repair and clearance pathways [11] This promotes the gradual accumulation of stressors, which correlates with increased disability, morbidity and inevitably death [11,12]. We summarise the most recent findings related to natural compounds that reportedly delay cellular senescence and/or prolong in vivo longevity by activating cytoprotective proteostatic mechanisms and/or the nuclear factor E2-related factor (Nrf2) anti-stress pathway
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
