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1.
Nat Commun ; 14(1): 8142, 2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38065964

RESUMEN

To ameliorate or even prevent signatures of aging in ultimately humans, we here report the identification of a previously undescribed polyacetylene contained in the root of carrots (Daucus carota), hereafter named isofalcarintriol, which we reveal as potent promoter of longevity in the nematode C. elegans. We assign the absolute configuration of the compound as (3 S,8 R,9 R,E)-heptadeca-10-en-4,6-diyne-3,8,9-triol, and develop a modular asymmetric synthesis route for all E-isofalcarintriol stereoisomers. At the molecular level, isofalcarintriol affects cellular respiration in mammalian cells, C. elegans, and mice, and interacts with the α-subunit of the mitochondrial ATP synthase to promote mitochondrial biogenesis. Phenotypically, this also results in decreased mammalian cancer cell growth, as well as improved motility and stress resistance in C. elegans, paralleled by reduced protein accumulation in nematodal models of neurodegeneration. In addition, isofalcarintriol supplementation to both wild-type C57BL/6NRj mice on high-fat diet, and aged mice on chow diet results in improved glucose metabolism, increased exercise endurance, and attenuated parameters of frailty at an advanced age. Given these diverse effects on health parameters in both nematodes and mice, isofalcarintriol might become a promising mitohormesis-inducing compound to delay, ameliorate, or prevent aging-associated diseases in humans.


Asunto(s)
Caenorhabditis elegans , Daucus carota , Humanos , Animales , Ratones , Caenorhabditis elegans/metabolismo , Mitocondrias/metabolismo , Ratones Endogámicos C57BL , Envejecimiento , Longevidad , Poliinos/metabolismo , Mamíferos
2.
Front Nutr ; 10: 1277343, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37904788

RESUMEN

As the global population continues to grow, the demand for dietary protein is rapidly increasing, necessitating the exploration of sustainable and nutritious protein sources. Algae has emerged as a promising food source due to their high value ingredients such as proteins, as well as for their environmental sustainability and abundance. However, knowledge gaps surrounding dietary recommendations and food applications restrict algae's utilization as a viable protein source. This review aims to address these gaps by assessing the suitability of both microalgae and macroalgae as alternative/complementary protein sources and exploring their potential applications in food products. The first section examines the potential suitability of algae as a major food source by analyzing the composition and bioavailability of key components in algal biomass, including proteins, lipids, dietary fiber, and micronutrients. Secondly, the biological effects of algae, particularly their impact on metabolic health are investigated with an emphasis on available clinical evidence. While evidence reveals protective effects of algae on glucose and lipid homeostasis as well as anti-inflammatory properties, further research is required to understand the longer-term impact of consuming algal protein, protein isolates, and concentrates on metabolic health, including protein metabolism. The review then explores the potential of algal proteins in food applications, including ways to overcome their sensory limitations, such as their dark pigmentation, taste, and odor, in order to improve consumer acceptance. To maximize algae's potential as a valuable protein source in the food sector, future research should prioritize the production of more acceptable algal biomass and explore new advances in food sciences and technology for improved consumer acceptance. Overall, this paper supports the potential utility of algae as a sustainable and healthy ingredient source for widespread use in future food production.

3.
Nat Commun ; 13(1): 107, 2022 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-35013237

RESUMEN

Aging is impacted by interventions across species, often converging on metabolic pathways. Transcription factors regulate longevity yet approaches for their pharmacological modulation to exert geroprotection remain sparse. We show that increased expression of the transcription factor Grainyhead 1 (GRH-1) promotes lifespan and pathogen resistance in Caenorhabditis elegans. A compound screen identifies FDA-approved drugs able to activate human GRHL1 and promote nematodal GRH-1-dependent longevity. GRHL1 activity is regulated by post-translational lysine methylation and the phosphoinositide (PI) 3-kinase C2A. Consistently, nematodal longevity following impairment of the PI 3-kinase or insulin/IGF-1 receptor requires grh-1. In BXD mice, Grhl1 expression is positively correlated with lifespan and insulin sensitivity. In humans, GRHL1 expression positively correlates with insulin receptor signaling and also with lifespan. Fasting blood glucose levels, including in individuals with type 2 diabetes, are negatively correlated with GRHL1 expression. Thereby, GRH-1/GRHL1 is identified as a pharmacologically malleable transcription factor impacting insulin signaling and lifespan.


Asunto(s)
Proteínas de Caenorhabditis elegans/genética , Fosfatidilinositol 3-Quinasas Clase II/genética , Diabetes Mellitus Tipo 2/genética , Factor I del Crecimiento Similar a la Insulina/genética , Insulina/metabolismo , Longevidad/genética , Proteínas Represoras/genética , Factores de Transcripción/genética , Animales , Animales Modificados Genéticamente , Glucemia/metabolismo , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/genética , Caenorhabditis elegans/crecimiento & desarrollo , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Fosfatidilinositol 3-Quinasas Clase II/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Regulación de la Expresión Génica , Humanos , Resistencia a la Insulina , Factor I del Crecimiento Similar a la Insulina/metabolismo , Longevidad/efectos de los fármacos , Metilación , Ratones , Papaverina/farmacología , Proteínas Represoras/metabolismo , Transducción de Señal , Factores de Transcripción/metabolismo , Vorinostat/farmacología
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