Selenocysteine mimics the effect of dietary restriction on lifespan via SKN‑1 and retards age‑associated pathophysiological changes in Caenorhabditis�elegans

Abstract

Selenocysteine, a sulfur-containing amino acid, can modulate cellular oxidative stress defense systems by incorporating into anti-oxidant enzymes such as glutathione peroxidase and thioredoxin reductase. Selenocysteine can also prevent cancer, neurodegenerative diseases and cardiovascular diseases. A recent study revealed that dietary supplementation with selenocysteine can increase the resistance of Caenorhabditis elegans to environmental stressors and its lifespan. The objective of the present study was to identify the underlying mechanism involved in the lifespan-extending effect of selenocysteine and the effect of selenocysteine on age-associated pathophysiological changes. Lifespan assays with known long-lived mutants of age-1 (the ortholog of the phosphoinositide 3-kinase), clk-1 (the ortholog of demethoxyubiquinone hydroxylase) and eat-2 (a ligand-gated ion channel subunit) revealed that the effect of selenocysteine on lifespan specifically overlapped with that of the eat-2 mutation, a genetic model of dietary restriction (DR). Selenocysteine mimicked the effect of DR on the bacterial dilution method. It required SKN-1 (the ortholog of mammalian nuclear factor-erythroid-related factor) for lifespan extension. In addition, selenocysteine significantly delayed the paralysis induced by human amyloid-β gene, positively correlated with the incidence of Alzheimer's disease. The effect of selenocysteine on amyloid-β-induced toxicity was dependent on the nuclear localization of DAF-16. Reduced survival caused by high-glucose-diet was recovered by selenocysteine. Selenocysteine also reduced the cellular level of reactive oxygen species known to be increased by high-glucose-diet. The results of the present study suggested that selenocysteine can mimic the effect of DR on lifespan and age-associated pathophysiological alterations, providing scientific evidence for the development of DR mimetics using selenocysteine.

Phosphatidylcholine Extends Lifespan via DAF-16 and Reduces Amyloid-Beta-Induced Toxicity inCaenorhabditis elegans

“…Resveratrol, a polyphenol compound rich in red wine, has been shown to have strong antioxidant and lifespan-extending effects on various model organisms [35]. Recent studies reported that amino acid derivatives, including N-acetyl-L-cysteine, S-allylcysteine, and selenocysteine, increase resistance to oxidative stress and extend lifespan in C. elegans [15, 16, 36]. In the present study, we showed that phosphatidylcholine, a phospholipid composing cellular membrane, had an antioxidant activity in vivo and conferred the longevity phenotype in C. elegans for the first time.…”

“…N-Acetyl-L-cysteine increased the resistance to environmental stresses and lifespan, mimicking dietary restriction [15]. Supplementation with selenocysteine conferred longevity phenotype and ameliorated age-related pathophysiological changes [16]. Extracts from Acanthopanax sessiliflorus , a plant used as a traditional treatment for many diseases, or Tenebrio molitor , an insect whose extracts have antibacterial, antifungal, and anticancer activities, also showed antioxidant and antiaging effect in C. elegans [17, 18].…”

The Relevance of Selenium Status in Rheumatoid Arthritis

“…Similar to the latter, it was recently reported that in Caenorhabditis elegans , the Sec mimics the effects of caloric restriction, which has shown benefits in lifespan and in age-related diseases. In this study, Sec was shown to mimic the effects of calorie restriction through SKN-1, the ortholog of nuclear factor erythroid 2-related factor 2 (NRF2) in mammalians, which regulates the expression of antioxidant proteins [ 150 ]. Although some of the aforementioned therapies, such as the Mediterranean diet and fasting, have shown favorable effects on some parameters of RA, more robust clinical trials are needed to generalize their recommendation; however, they are still promising proposals for accompanying drug therapy in RA patients.…”

Potential ofCaenorhabditis elegansas an antiaging evaluation model for dietary phytochemicals: A review

“…Selenocysteine plays an important role in cellular oxidative stress defense systems and preventing neurovegetative diseases. Selenocysteine has recently been shown to mimic the effects of DR on lifespan and age‐related pathophysiological changes by SKN‐1 but is not dependent on DAF‐16 (Kim, Kim, & Park, 2018). Sesamin is derived from sesame seeds and exerts antiaging effects (Yaguchi et al., 2014).…”

“…d ‐allulose, an isomer of d ‐fructose, also increased the lifespan of nematodes and mimic DR response in the organism (Kim, Kim, & Park, 2018a). A study found that Ayurvedic polyherbal extract (PHE) at a low dose of 0.01 µg/mL increased the mean lifespan of C. elegans by 16.09% (Rathor, Pant, Awasthi, Mani, & Pandey, 2017).…”