Nutraceutical and Dietary Strategies for Up-Regulating Macroautophagy

Abstract

Macroautophagy is a “cell cleansing” process that rids cells of protein aggregates and damaged organelles that may contribute to disease pathogenesis and the dysfunctions associated with aging. Measures which boost longevity and health span in rodents typically up-regulate macroautophagy, and it has often been suggested that safe strategies which can promote this process in humans may contribute to healthful aging. The kinase ULK1 serves as a trigger for autophagy initiation, and the transcription factors TFEB, FOXO1, ATF4 and CHOP promote expression of a number of proteins which mediate macroautophagy. Nutraceutical or dietary measures which stimulate AMPK, SIRT1, eIF5A, and that diminish the activities of AKT and mTORC1, can be expected to boost the activities of these pro-autophagic factors. The activity of AMPK can be stimulated with the phytochemical berberine. SIRT1 activation may be achieved with a range of agents, including ferulic acid, melatonin, urolithin A, N1-methylnicotinamide, nicotinamide riboside, and glucosamine; correction of ubiquinone deficiency may also be useful in this regard, as may dietary strategies such as time-restricted feeding or intermittent fasting. In the context of an age-related decrease in cellular polyamine levels, provision of exogenous spermidine can boost the hypusination reaction required for the appropriate post-translational modification of eIF5A. Low-protein plant-based diets could be expected to increase ATF4 and CHOP expression, while diminishing IGF-I-mediated activation of AKT and mTORC1. Hence, practical strategies for protecting health by up-regulating macroautophagy may be feasible.

Combined pulses of light and sound in the retina with nutraceuticals may enhance the recovery of foveal holes

“…Recently, a powerful effect of combined autophagy-inducing photomodulation by light therapy and its combination with autophagy inducers phytochemicals was described (Pinelli et al, 2021). Since light at specific wavelengths strongly activates autophagy (Suárez-Barrio et al, 2021), this is expected to synergize with establish autophagy activators such as specific phytochemicals (McCarty, 2022). The former represents the natural light, which depending on the specific wavelengths, apart from generating the process of vision, induces autophagy and it is key in removing mitochondria and altered proteins (Pevna et al, 2021;Stefenon et al, 2021;Yang et al, 2021).…”

Autophagy in Its (Proper) Context: Molecular Basis, Biological Relevance, Pharmacological Modulation, and Lifestyle Medicine

“…Diet is a major modulator of autophagy. More specifically, available literature distinguishes between specific nutrients present in certain groups of foods or in the form of supplementation and specific dietary strategies such as caloric restriction and intermittent fasting 195 , 196 . All these components can directly act through the biochemical regulation of different products such as AMPK, SIRT-1, eIF5A, or GCN2, ultimately leading to the modulation of the main proteins implicated in the autophagy process like ULK1, TFEB, FOXO1, ATF-4 or CHOP 195 .…”

“…Not only isolated nutrients but also those contained in foods are important modulators of autophagy. Plant foods are perhaps the major modulators of these processes, especially regarding their content in a broad spectrum of nutrients involved in the regulation of this process, such as vitamins and several bioactive compounds 195 , 202 . After plants, foods like fish and seafood, eggs, and in general, different groups of food commonly consumed in healthy dietary patterns such as Mediterranean Diet (Med Diet) have also significant effects on upregulating autophagy 203 , 204 .…”

Autophagic mechanisms in longevity intervention: role of natural active compounds

“…Finally, in the degradation stage, the autophagosome fuses with the lysosomal membrane and the autophagic cargo is sequestered by lysosomal hydrolases (Refs 15 , 16 , 17 ). In macroautophagy and microautophagy (also called endosomal microautophagy in mammals), cargo transport to the lysosome is vesicle-mediated, whereas in CMA it occurs through specific receptors (Refs 18 , 19 ). In CASA, which is one of the selective macroautophagy types, polyubiquitinated aggregate proteins are transmitted to the autophagosome by helper chaperone Bcl2-related athanogen 3 (Bag3) and cytosolic chaperone heat shock cognate 70 kDa protein (HSC70) without binding to a pentapeptide amino acid motif (KFERQ)-like motif (Ref.…”