lifespan extension
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BMC Nutrition ◽  
2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Samantha Hughes ◽  
Nikki Kolsters ◽  
David van de Klashorst ◽  
Emanuel Kreuter ◽  
Karin Berger Büter

Abstract Background Members of the Rosaceae, Solanaceae and Zingiberaceae families which include fruits such as cherries, tomatoes and ginger are known to have health promoting effects. There is growing interest in consuming these “functional foods” as a means to increase health and healthy ageing. However, many studies explore the effect of these foods in isolation, not as a blend of multiple functional foods. Methods In this study, an extract containing the dried berries, fruits, and roots of members of these families was prepared, which we called Bioact®180. The nematode Caenorhabditis elegans was used to evaluate the effects of Bioact®180 on lifespan and health endpoints, including muscle and mitochondria structure and locomotion. Results Exposure to the 1000 µg/mL of Bioact®180 extract, containing 4% total phenols, were healthier, as observed by an increase in mean lifespan with and small but significant increase in maximal lifespan. Nematodes exposed to Bioact®180 displayed better mobility in mid-life stages as well as enhanced mitochondrial morphology, which was more comparable to younger animals, suggesting that these worms are protected to some degree from sarcopenia. Conclusions Together, our findings reveal that Bioact®180, a blend of fruits and roots from Rosaceae, Solanaceae and Zingiberaceae family members has anti-aging effects. Bioact®180 promotes health and lifespan extension in C. elegans, corresponding to functional improvements in mobility.


2022 ◽  
Vol 8 ◽  
Author(s):  
Haitao Zhou ◽  
Shanshan Ding ◽  
Chuanxin Sun ◽  
Jiahui Fu ◽  
Dong Yang ◽  
...  

Lycium barbarum berry (Ningxia Gouqi, Fructus lycii, goji berry, or wolfberry), as a traditional Chinese herb, was recorded beneficial for longevity in traditional Chinese medical scriptures and currently is a natural dietary supplement worldwide. However, under modern experimental conditions, the longevity effect of L. barbarum berry and the underlying mechanisms have been less studied. Here, we reported that total water extracts of L. barbarum berry (LBE), which contains 22% polysaccharides and other components, such as anthocyanins, extended the lifespan of Caenorhabditis elegans without side effects on worm fertility and pharyngeal pumping. Interestingly, we found that the lifespan extension effect was more prominent in worms with shorter mean lifespan as compared to those with longer mean lifespan. Furthermore, we showed that the lifespan extension effect of LBE depended on deacetylase sir-2.1. Remarkably, LBE rescued heat shock transcription factor-1 (hsf-1) deficiency in wild-type worms with different mean lifespans, and this effect also depended on sir-2.1. In addition, we found that LBE extended lifespan and alleviated toxic protein aggregation in neurodegenerative worms with hsf-1 deficiency. Our study suggested that LBE may be a potential antiaging natural dietary supplement especially to individuals with malnutrition or chronic diseases and a potential therapeutic agent for neurodegenerative diseases characterized by hsf-1 deficiency.


2021 ◽  
Author(s):  
Javier Huayta ◽  
Adriana San-Miguel

In many organisms, dietary restriction (DR) leads to lifespan extension through the activation of cell protection and pro-longevity gene expression programs. In the nematode C. elegans, the DAF-16 transcription factor is a key aging regulator that governs the Insulin/IGF-1 signaling pathway and undergoes translocation from the cytoplasm to the nucleus of cells when animals are exposed to food limitation. In this work, we assess the endogenous activity of DAF-16 under various DR regimes by coupling CRISPR/Cas9-enabled fluorescent tagging of DAF-16 with quantitative image analysis and machine learning. Our results indicate that lifelong DAF-16 endogenous activity is a robust predictor of mean lifespan in C. elegans, and it accounts for 78% of the lifespan variability induced by DR. We found that this lifespan-extending mechanism occurs mainly in the intestine and neurons, and that DR drives DAF-16 activity in unexpected locations such as the germline and intestinal nucleoli.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 684-684
Author(s):  
Raul Castro-Portuguez ◽  
Jeremy Meyers ◽  
Sam Freitas ◽  
Hope Dang ◽  
Emily Turner ◽  
...  

Abstract Aging is characterized by a progressive decline in the normal physiological functions of an organism, ultimately leading to mortality. Metabolic changes throughout the aging process disrupt the balance and homeostasis of the cell. The kynurenine metabolic pathway is the sole de novo biosynthetic pathway for producing NAD+ from ingested tryptophan. Altered kynurenine pathway activity is associated with both aging and a variety of age-associated diseases, and kynurenine-based interventions can extend lifespan in Caenorhabditis elegans. Our laboratory recently demonstrated knockdown of the kynurenine pathway enzymes kynureninase (KYNU) or 3-hydroxyanthranilic acid dioxygenase (HAAO) increases lifespan by 20-30% in C elegans. However, the mechanism of how these interventions may modulate response against different stressors during the aging process has yet to be explored. Fluorescent reporter strains show the stress-responsive transcription factors skn-1 (ortholog of NRF2/NFE2L2; oxidative stress response) and hif-1 (ortholog of HIF1A; hypoxic stress response) to be highly upregulated when the kynurenine pathway is inhibited. We also demonstrated the increase expression of gst-4 and gcs-1 (transcriptional targets skn-1), which are involved in production of the antioxidant glutathione (GSH), as well as upregulation of cysl-2 (transcriptional target of hif-1), a regulator of cysteine biosynthesis from serine. We hypothesize that lifespan extension resulting from kynurenine pathway inhibition is mediated, at least in part, by upregulation of these transcription factors, providing elevated defense against oxidative stress and hypoxic stress.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 682-682
Author(s):  
Bohan Zhang ◽  
David Lee ◽  
Alexander Tyshkovskiy ◽  
Akshay Bareja ◽  
Csaba Kerepesi ◽  
...  

Abstract Heterochronic parabiosis is a powerful rejuvenation model in aging research. Due to limitations in the duration of blood sharing and/or physical attachment, it is currently unclear if parabiosis retards the molecular signatures of aging or affects healthspan/lifespan in the mouse. Here, we describe a long-term heterochronic parabiosis model, which appears to slow down the aging process. We observed a “deceleration” of biological age based on molecular aging biomarkers estimated with DNA methylation clock and RNA-seq signature analysis. The slowing of biological aging was accompanied by systemic amelioration of aging phenotypes. Consistent with these findings, we found that aged mice, which underwent heterochronic parabiosis, had an increased healthspan and lifespan. Overall, our study re-introduces a prolonged parabiosis and detachment model as a novel rejuvenation therapy, suggesting that a systemic reset of biological age in old organisms can be achieved through the exposure to young environment.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 562-562
Author(s):  
Sudipta Bar ◽  
George Brownridge ◽  
Jennifer Beck ◽  
Rachel Brem ◽  
Hugo Bellen ◽  
...  

Abstract Dietary restriction (DR) is the most robust method to delay aging and the onset of neurogenerative disorders across multiple species, though the mechanisms behind this phenomenon remain unknown. To elucidate how DR mediates lifespan extension, we analyzed natural genetic variants that associate with increased longevity under DR conditions in the Drosophila Genetic Reference Panel. We found that neuronal expression of the fly homolog of human Oxidation Resistance 1 (OXR1) is necessary for DR-mediated lifespan extension. Neuronal knockdown of OXR1 also accelerated visual decline but not physical decline, arguing for a specific role of OXR1 in neuronal signaling. Further, we find that overexpression of the TLDc domain from human OXR1 is sufficient for lifespan extension in a diet-dependent manner. Studies from the Accelerating Medicines Partnership - Alzheimer's Disease network show that patients with reduced OXR1 protein levels are more prone to Alzheimer's disease diagnosis, and we find that overexpression of human OXR1 is protective in animal and cell Alzheimer's models. In seeking the mechanism by which OXR1 protects against age-related neuronal decline, we discovered that it provides a necessary function in regulating the neuronal retromer complex, which is essential for the recycling of transmembrane receptors and for maintenance of autophagy. We further discovered that OXR1 deficiency can be rescued by genetic or pharmacological enhancement of retromer function, and that this enhancement extends lifespan and healthspan. Understanding how OXR1 operates could help uncover novel mechanisms to slow neurodegeneration including Alzheimer's disease.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 116-116
Author(s):  
Filipa Rijo-Ferreira ◽  
Mariko Izumo ◽  
Pin Xu ◽  
Carla B Green ◽  
Joseph S Takahashi

Abstract Caloric restriction (CR) promotes longevity in several species. Classic CR protocols often lead to chronic cycles of 2h-feeding/22h-fasting, raising the question whether calories, fasting or time of day are causal. To address this, we tested an AL control group and five CR protocols with different timing and duration of feeding/fasting cycles. C57BL/6J male mice were subjected to 30% CR as one single meal a day at the beginning of the day or night (classical protocols with < 2h feeding, CR-day and CR-night), or smaller meals distributed for 12h (CR-day-12h and CR-night-12h), or evenly spread out throughout 24h (CR-spread) to abolish the otherwise daily feeding pattern adopted by nocturnal animals. We found that CR alone is sufficient to extend lifespan without fasting. However, the benefits are enhanced if feeding/fasting cycles are present and match their normal nocturnal activity. Circadian alignment of feeding with at least 12h fasting boosts CR-mediated increase on survival in mice, independently body weight. Aging leads to widespread upregulation of inflammation-related genes and downregulation of metabolic pathways in liver from ad lib fed mice; whereas CR at night ameliorates these aging-related changes and preserves circadian oscillations in gene expression. Overall, our results demonstrate that circadian interventions promote longevity and provide a novel perspective for elucidating mechanisms of aging.


2021 ◽  
Vol 22 (23) ◽  
pp. 12873
Author(s):  
Dmitry L. Maslov ◽  
Nadezhda V. Zemskaya ◽  
Oxana P. Trifonova ◽  
Steven Lichtenberg ◽  
Elena E. Balashova ◽  
...  

The increase in life expectancy, leading to a rise in the proportion of older people, is accompanied by a prevalence of age-related disorders among the world population, the fight against which today is one of the leading biomedical challenges. Exploring the biological insights concerning the lifespan is one of the ways to provide a background for designing an effective treatment for the increase in healthy years of life. Untargeted direct injection mass spectrometry-based metabolite profiling of 12 species of Drosophila with significant variations in natural lifespans was conducted in this research. A cross-comparison study of metabolomic profiles revealed lifespan signatures of flies. These signatures indicate that lifespan extension is associated with the upregulation of amino acids, phospholipids, and carbohydrate metabolism. Such information provides a metabolome-level view on longevity and may provide a molecular measure of organism age in age-related studies.


2021 ◽  
Author(s):  
Bohan Zhang ◽  
David E Lee ◽  
Alexandre Trapp ◽  
Alexander Tyshkovskiy ◽  
Ake T Lu ◽  
...  

Heterochronic parabiosis (HPB) is known for its functional rejuvenation effects across several mouse tissues. However, its impact on the biological age of organisms and their long-term health remains unknown. Here, we performed extended (3-month) HPB, followed by a 2-month detachment period of anastomosed pairs. Old detached mice exhibited improved physiological parameters and lived longer than control isochronic mice. HPB drastically reduced the biological age of blood and liver based on epigenetic analyses across several clock models on two independent platforms; remarkably, this rejuvenation effect persisted even after 2 months of detachment. Transcriptomic and epigenomic profiles of anastomosed mice showed an intermediate phenotype between old and young, suggesting a comprehensive multi-omic rejuvenation effect. In addition, old HPB mice showed transcriptome changes opposite to aging, but akin to several lifespan-extending interventions. Altogether, we reveal that long-term HPB can decrease the biological age of mice, in part through long-lasting epigenetic and transcriptome remodeling, culminating in the extension of lifespan and healthspan.


2021 ◽  
Author(s):  
Tatiana V Villalobos ◽  
Bhaswati Ghosh ◽  
Sanaa Alam ◽  
Tyler J Butsch ◽  
Brennan M Mercola ◽  
...  

Dietary restriction promotes longevity via autophagy activation. However, changes to lysosomes underlying this effect remain unclear. Using the nematode Caenorhabditis elegans, we show that induction of autophagic tubular lysosomes, which occurs upon dietary restriction or mTOR inhibition, is a critical event linking reduced food intake to lifespan extension. We find that starvation induces tubular lysosomes not only in affected individuals but also in well-fed descendants, and the presence of gut tubular lysosomes in well-fed progeny is predictive of enhanced lifespan. Furthermore, we demonstrate that expression of Drosophila SVIP, a tubular-lysosome activator in flies, artificially induces tubular lysosomes in well-fed worms and improves C. elegans health in old age. These findings identify tubular lysosomes as a new class of lysosomes that couples starvation to healthy aging.


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