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Trigonelline is the main alkaloid with bioactivity presented in fenugreek, which was used in traditional medicine in Asian countries for centuries. It is reported that trigonelline has anti-inflammatory, anti-oxidant, and anti-pathogenic effects. We are wondering whether trigonelline have anti-aging effect. We found that 50  μ M of trigonelline had the best anti-aging activity and could prolong the lifespan of Caenorhabditis elegans ( C. elegans ) by about 17.9%. Trigonelline can enhance the oxidative, heat, and pathogenic stress resistance of C. elegans . Trigonelline could also delay the development of neurodegenerative diseases, such as AD, PD, and HD, in models of C. elegans . Trigonelline could not prolong the lifespan of long-lived worms with loss-of-function mutations in genes regulating energy and nutrition, such as clk-1 , isp-1 , eat-2 , and rsks-1 . Trigonelline requires daf-16 , hsf-1 , and aak-2 to extend the lifespan of C. elegans . Trigonelline can also up-regulate the expression of daf-16 and hsf-1 targeted downstream genes, such as sod-3 , gst-4 , hsp-16.1 , and hsp-12.6 . Our results can be the basis for developing trigonelline-rich products with health benefits, as well as for further research on the pharmacological usage of trigonelline., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2021 Wen-Yu Zeng et al.)

Naringin is a dihydroflavonoid, which is rich in several plant species used for herbal medicine. It has a wide range of biological activities, including antineoplastic, anti-inflammatory, antiphotoaging, and antioxidative activities. So it would be interesting to know if naringin has an effect on aging and aging-related diseases. We examined the effect of naringin on the aging of Caenorhabditis elegans ( C . elegans ). Our results showed that naringin could extend the lifespan of C . elegans . Moreover, naringin could also increase the thermal and oxidative stress tolerance, reduce the accumulation of lipofuscin, and delay the progress of aging-related diseases in C . elegans models of AD and PD. Naringin could not significantly extend the lifespan of long-lived mutants from genes in insulin/IGF-1 signaling (IIS) and nutrient-sensing pathways, such as daf - 2 , akt - 2 , akt - 1 , eat - 2 , sir - 2 . 1 , and rsks - 1 . Naringin treatment prolonged the lifespan of long-lived glp - 1 mutants, which have decreased reproductive stem cells. Naringin could not extend the lifespan of a null mutant of the fox-head transcription factor DAF-16. Moreover, naringin could increase the mRNA expression of genes regulated by daf - 16 and itself. In conclusion, we show that a natural product naringin could extend the lifespan of C . elegans and delay the progression of aging-related diseases in C . elegans models via DAF-16., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2020 Qing Zhu et al.)

Competing Interests: The authors declare no conflict of interest.

In Caenorhabditis elegans (C. elegans) , ablation of germline stem cells (GSCs) leads to infertility, which extends lifespan. It has been reported that aging and reproduction are both inextricably associated with metabolism. However, few studies have investigated the roles of polar small molecules metabolism in regulating longevity by reproduction. In this work, we combined the nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to profile the water-soluble metabolome in C. elegans . Comparing the metabolic fingerprint between two physiological ages among different mutants, our results demonstrate that aging is characterized by metabolome remodeling and metabolic decline. In addition, by analyzing the metabolic profiles of long-lived germline-less glp-1 mutants, we discovered that glp-1 mutants regulate the levels of many age-variant metabolites to attenuate aging, including elevated concentrations of the pyrimidine and purine metabolism intermediates and decreased concentrations of the citric acid cycle intermediates. Interestingly, by analyzing the metabolome of daf-16;glp-1 double mutants, our results revealed that some metabolic exchange contributing to germline-mediated longevity was mediated by transcription factor FOXO/DAF-16, including pyrimidine metabolism and the TCA cycle. Based on a comprehensive metabolic analysis, we provide novel insight into the relationship between longevity and metabolism regulated by germline signals in C. elegans .

Aging is a major risk factor for many prevalent diseases. Pharmacological intervention to improve the health span and extend the lifespan could be a preventive elixir for aging and age-related diseases. The non-steroid anti-inflammation medicine aspirin was reported to delay aging in Caenorhabditis elegans (C. elegans) and mice. We are wondering if the analogues of aspirin could also present antiaging activity. Here, we synthesized several aspirin derivatives and investigated their thermotolerance and antiaging effect in C. elegans. One of the compounds, 5-(bis(3-methylbut-2-en-1-yl)amino)-2-hydroxybenzoic acid, moderately increased the survival of C. elegans under heat stress, but could not extend the lifespan under optimum conditions. This compound could increase the mRNA level of stress response gene gst-4, and the mRNA and protein expression level of heat shock protein hsp-16.2 under heat stress. The failure of activating the transcription factor DAF-16 might explain why this compound could not act as aspirin to extend the lifespan of C. elegans. Our results would help further the investigation of the pharmacological activity of aspirin analogues and the relationship between structures and activity. [ABSTRACT FROM AUTHOR]

The abrogation of the germ cells in Caenorhabditis elegans ( C. elegans ) by either genetic means or cell ablation results in about 60% increase of longevity. Upon the inhibition of germline stem cell proliferation, certain signaling molecules inhibit the target of rapamycin (TOR), activate the transcription factors including DAF-16, DAF-12, and PHA-4, leading to altered fatty acid lipolysis, autophagy, stress resistance, and the extended lifespan. But the exact cascades and interactions of those signaling pathways are still obscure. To understand how the reproductive system affects aging at the protein level, we determined the protein expression profile of the long-lived temperature-sensitive mutant glp-1(e2141) and wild-type N2 using isobaric tags for relative and absolute quantitation (iTRAQ) technology. Our results showed that the abundance of proteins relevant to transcription, RNA processing, translation, protein folding, and proteolytic process were decreased, while collagen proteins and proteins involved in detoxification and innate immune responses were increased in C. elegans glp-1 mutant, these alterations of protein abundance might attenuate protein metabolism and enhance immune response and stress resistance, and finally contribute to germline-mediated longevity. Biological significance This study provides an overview of the altered protein expression upon germline ablation. Germ-cell loss results in decreased abundance of proteins involved in protein synthesis and breakdown, and increased abundance of proteins involved in detoxification and immune response, suggesting that protein synthesis and metabolism might be attenuated, while detoxification and immune responses might be increased. The altered protein abundance might result in physiological adaptations that contribute to extended longevity in germline-deficient C. elegans . This study brings new light on the role of reproductive control of lifespan. [ABSTRACT FROM AUTHOR]

D-chiro-inositol (DCI) is an isomer of inositol, abundant in many foods, such as beans and buckwheat, with insulin-sensitizing, anti-inflammatory, and antioxidant effects. DCI has been used to relieve insulin resistance in diabetes and polycystic ovary syndrome in combination with inositol or D-pinitol. Here, we investigated the effect of DCI on aging and stress resistance in C. elegans. We found that DCI could prolong the lifespan of C. elegans by up to 29.6 %. DCI significantly delayed the onset of neurodegenerative diseases in models of C. elegans. DCI decreased the accumulation of Aβ 1 – 42 , alpha-synuclein, and poly-glutamine, the pathological causes of Alzheimer's, Parkinson's, and Huntington's diseases, respectively. DCI significantly increased the stress resistances against pathogens, oxidants and heat shock. Moreover, D-chiro-inositol reduced the content of ROS and malondialdehyde by increasing the total antioxidant capacity and the activity of superoxide dismutase and catalase. Above effects of DCI requires the transcription factors FOXO/DAF-16 and Nrf-2/SKN-1. DCI also increased the expression of downstream genes regulated by FOXO/DAF-16 and Nrf-2/SKN-1. In conclusion, DCI enhanced the antioxidant capacity and healthy lifespan of C. elegans by activating DAF-16, SKN-1, and HSF-1. Our results showed that DCI could be a promising antiaging agent that is worth further research on the mechanism and health supplemental application of DCI. • D-chiro-inositol extends the lifespan and slows the aging-related phenotypes of C. elegans. • D-chiro-inositol delays the development of neurodegenerative diseases in models of C. elegans. • D-chiro-inositol enhances the healthy lifespan of C. elegans by activating DAF-16, SKN-1/NRF-2, and HSF-1. [ABSTRACT FROM AUTHOR]