Initiating PeriCBD to probe perinatal influences on neurodevelopment during 3-10 years in China.

Adverse perinatal factors can interfere with the normal development of the brain, potentially resulting in long-term effects on the comprehensive development of children. Presently, the understanding of cognitive and neurodevelopmental processes under conditions of adverse perinatal factors is substantially limited. There is a critical need for an open resource that integrates various perinatal factors with the development of the brain and mental health to facilitate a deeper understanding of these developmental trajectories. In this Data Descriptor, we introduce a multicenter database containing information on perinatal factors that can potentially influence children's brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development associated with perinatal factors among children aged 3-10 years. Ultimately, our goal is to help understand how different adverse perinatal factors specifically impact cognitive development and neurodevelopment. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD.

Nanoliposome-Mediated Encapsulation of Chlorella Oil for the Development of a Controlled-Release Lipid-Lowering Formulation.

Chlorella oil nanoliposomes (CO-NLP) were synthesized through ultrasonic injection with ethanol, and their physicochemical properties and hypolipidemic efficacy were systematically investigated. The results revealed that the mean particle size of CO-NLP was 86.90 nm and the encapsulation efficiency (EE) was 92.84%. Storage conditions at 4 °C were conducive to the stability of CO-NLP, maintaining an EE of approximately 90% even after 10 days of storage. The release profile of CO-NLP adhered more closely to the first-order kinetic model during in vitro assessments, exhibiting a slower release rate compared to free microalgae oil. In simulated in vitro digestion experiments, lipolytic reactions of CO-NLP were observed during intestinal digestion subsequent to nanoliposome administration. Notably, the inhibitory effect of CO-NLP on cholesterol esterase activity was measured at 85.42%. Additionally, the average fluorescence intensity of nematodes in the CO-NLP group was 52.17% lower than in the control group at a CO-NLP concentration of 500 µg/mL, which suggests a pronounced lipid-lowering effect of CO-NLP. Therefore, the CO-NLP exhibited characteristics of small and uniform particle size, elevated storage stability, gradual release during intestinal digestion, and a noteworthy hypolipidemic effect. These findings designate CO-NLP as a novel lipid-lowering active product, demonstrating potential for the development of functional foods.

Role and Potential Mechanisms of Nicotinamide Mononucleotide in Aging.

Nicotinamide adenine dinucleotide (NAD+) has recently attracted much attention due to its role in aging and lifespan extension. NAD+ directly and indirectly affects many cellular processes, including metabolic pathways, DNA repair, and immune cell activities. These mechanisms are critical for maintaining cellular homeostasis. However, the decline in NAD+ levels with aging impairs tissue function, which has been associated with several age-related diseases. In fact, the aging population has been steadily increasing worldwide, and it is important to restore NAD+ levels and reverse or delay these age-related disorders. Therefore, there is an increasing demand for healthy products that can mitigate aging, extend lifespan, and halt age-related consequences. In this case, several studies in humans and animals have targeted NAD+ metabolism with NAD+ intermediates. Among them, nicotinamide mononucleotide (NMN), a precursor in the biosynthesis of NAD+, has recently received much attention from the scientific community for its anti-aging properties. In model organisms, ingestion of NMN has been shown to improve age-related diseases and probably delay death. Here, we review aspects of NMN biosynthesis and the mechanism of its absorption, as well as potential anti-aging mechanisms of NMN, including recent preclinical and clinical tests, adverse effects, limitations, and perceived challenges.

Global risk factor analysis of myopia onset in children: A systematic review and meta-analysis.

INTRODUCTION: This work aimed to comprehensively assess the risk factors affecting myopia in children to develop more effective prevention and treatment strategies. To this end, data from database were employed to assess the relationship between the incidence of myopia and its risk factors. METHODS: We searched eight databases online in June 2022. Cohort studies were included that measured the connection between risk factors and myopia. Eligibility was not restricted by language. The Newcastle-Ottawa Scale (NOS) was used to measure the risk of bias and conducted GRADE evaluation to determine the certainty of evidence. Potential risk factors with positive or negative results were seen. Inplasy Registration: https://inplasy.com/inplasy-2022-4-0109/. RESULTS: Evidence that risk factors for myopia are mixed, comprising both positive (20) and null (17) findings. In 19 cohort studies on 3578 children, girls were more likely to develop myopia (RR: 1.28 [1.22-1.35]). Myopia can occur at any age, from early childhood to late adulthood. Children whose parents had myopia were more likely to develop myopia. Longer outdoor activities time (RR: 0.97 [0.95-0.98]) and less near-work time (RR: 1.05 [1.02-1.07]) appeared to be significantly decrease the incidence of myopia. Children with lower SE, longer AL, a lower magnitude of positive relative accommodation, worse presenting visual acuity, deeper anterior chamber, and thinner crystalline lens may be related to myopia onset. The burden of myopia in underprivileged countries is higher than in developed countries (RR: 5.28 [2.06-13.48]). The quality of evidence for the evaluated factors was moderate to low or very low. CONCLUSIONS: Genetic factors, environmental factors (such as excessive use of electronic products, and poor study habits) and lifestyle factors (such as lack of outdoor activities, poor nutrition, etc.) are the main risk factors for myopia in children. Myopia prevention strategies should be designed based on environmental factors, gender, parental myopia and eye indicators in order to explore a lifestyle that is more conducive to the eye health of children.

Pseudomyopia as an independent risk factor for myopia onset: a prospective cohort study among school-aged children.

AIM: To investigate whether pseudomyopia is an independent risk factor for myopia onset based on a population-based cohort study. METHODS: Non-myopic children were recruited from schools in rural and urban settings of Shangdong province, China. Baseline examinations started in September 2020 and all participants were invited for a 6-month follow-up. Pseudomyopia was defined as spherical equivalent (SE) ≤-0.50 diopters (D) before cycloplegia and >-0.50D after cycloplegia. Myopia was defined as cycloplegic SE ≤-0.50D. RESULTS: A total of 2328 children (baseline age: 4-17 years) were included in the final analysis. During the 6-month follow-up, 21.1% (355/1680) pseudomyopic eyes developed myopia, and 3.8% (110/2879) non-myopic and non-pseudomyopic eyes developed myopia. After adjusting for multiple myopia risk factors, including baseline cycloplegic SE, near work and outdoor time, pseudomyopia was found to be an independent risk factor for myopia onset (relative risk=2.52, 95% CI 1.86 to 3.42). Additionally, pseudomyopic children with more myopic cycloplegic SE (p<0.001), smaller difference between cycloplegic and non-cycloplegic SE (DIFF, p<0.001), and higher binocular amplitude of accommodation (p<0.001) had higher risk of myopia development. CONCLUSION: This is an important longitudinal study to prove that pseudomyopia is an independent risk factor for myopia development among school-aged children.

Characteristics of full compensation and its association with total astigmatism: A cross-sectional study.

Objective: To evaluate the characteristics of full compensation and its association with the prevalence of total astigmatism (TA), and to analyze the effects of TA on uncorrected distance visual acuity (UDVA). Methods: With random cluster sampling based on a school-based cross-sectional design, children aged 4 to 18 years were recruited in September 2020, Shandong Province, China. TA, anterior corneal astigmatism (ACA), and ocular residual astigmatism (ORA) were converted to vectorial components (J0, J45), followed by an assessment of the compensatory effect of ACA by ORA. Astigmatism was defined as a cylinder that was better than or equal to 0.75 diopters (D). Logistic regression analysis was used to assess the related factors for children with full compensation, and the generalized linear model was used to assess the influence of TA on UDVA. Results: Out of 4,494 eligible children, data of 4,145 children (92.3%, 9.23 ± 3.15 years, 50.4% boys) were included in the statistical analysis. The prevalence of TA (27.9%) increased significantly with age (Ptrend < 0.001). The distribution of full compensation in J0 and J45 components were similar (22.1% and 25.6%, respectively), which decreased with age (Ptrend < 0.001). The closer the refractive status was to emmetropization, the higher the proportion of full compensation and the lower the prevalence of TA were. Shorter axial length (J0: Odds Ratio (OR) = 0.76, 95% confidence interval (CI): 0.61 to 0.94, P = 0.010), better UDVA (J0: OR = 0.37, 95% CI: 0.21 to 0.65, P < 0.001; J45: OR = 0.34, 95% CI: 0.20 to 0.59, P < 0.001), and longer average corneal curvature radius (J0: OR = 3.72, 95% CI: 2.18 to 6.34, P < 0.001; J45: OR = 2.82, 95% CI: 1.67 to 4.76, P < 0.001) were associated with full compensation. Higher TA was associated with a worse UDVA (ß = 0.03, 95% CI: 0.02 to 0.04, P < 0.001). Conclusions: The prevalence of TA gradually increased with age, and showed a U-shaped distribution with increased refraction. Full compensation was associated with smaller TA and better UDVA. This indicated that considering the compensatory effect of ORA is vital for astigmatism correction in clinical work, which may improve the visual quality.

Fe-N-C catalysts decorated with oxygen vacancies-rich CeOx to increase oxygen reduction performance for Zn-air batteries.

Platinum group metal (PGM)-free catalysts represented by nitrogen and iron co-doped carbon (Fe-N-C) catalysts are desirable and critical for metal-air batteries, but challenges still exist in performance and stability. Here, cerium oxides (CeOx) are incorporated into a two-dimensional Fe-N-C catalyst (FeNC-Ce-950) via a host-guest strategy. The Ce4+/Ce3+ redox system creates a large number of oxygen vacancies for rapid O2 adsorption to accelerate the kinetics of oxygen reduction reaction (ORR). Consequently, the as-synthesized FeNC-Ce-950 catalyst exhibits a half-wave potential (E1/2) of 0.921 V and negligible decay (<2 mV for ΔE1/2) after 5,000 accelerated durability cycles, significantly outperforming most of ORR catalysts reported in recent years and precious metal counterparts. When applied in a zinc-air battery, it demonstrates a peak power density of 175 mW cm-2 and a specific capacity of 757 mAh gZn-1. This study also provides a reference for the exploration of Fe-N-C catalysts decorated with variable valence metal oxides.

An antisteatosis response regulated by oleic acid through lipid droplet-mediated ERAD enhancement.

Although excessive lipid accumulation is a hallmark of obesity-related pathologies, some lipids are beneficial. Oleic acid (OA), the most abundant monounsaturated fatty acid (FA), promotes health and longevity. Here, we show that OA benefits Caenorhabditis elegans by activating the endoplasmic reticulum (ER)-resident transcription factor SKN-1A (Nrf1/NFE2L1) in a lipid homeostasis response. SKN-1A/Nrf1 is cleared from the ER by the ER-associated degradation (ERAD) machinery and stabilized when proteasome activity is low and canonically maintains proteasome homeostasis. Unexpectedly, OA increases nuclear SKN-1A levels independently of proteasome activity, through lipid droplet-dependent enhancement of ERAD. In turn, SKN-1A reduces steatosis by reshaping the lipid metabolism transcriptome and mediates longevity from OA provided through endogenous accumulation, reduced H3K4 trimethylation, or dietary supplementation. Our findings reveal an unexpected mechanism of FA signal transduction, as well as a lipid homeostasis pathway that provides strategies for opposing steatosis and aging, and may mediate some benefits of the OA-rich Mediterranean diet.

Morusin and mulberrin extend the lifespans of yeast and C. elegans via suppressing nutrient-sensing pathways.

Compounds with lifespan extension activity are rare, although increasing research efforts have been invested in this field to find ways to extend healthy lifespan. By applying a yeast-based high-throughput assay to identify the chronological lifespan extension activity of mulberry extracts rapidly, we demonstrated that a group of prenylated flavones, particularly morusin and mulberrin, could extend the chronological lifespan of budding yeast via a nutrient-dependent regime by at least partially targeting SCH9. Their antiaging activity could be extended to C. elegans by promoting its longevity, dependent on the full functions of genes akt-1 or akt-2. Moreover, additional benefits were observed from morusin- and mulberrin-treated worms, including increased reproduction without the influence of worm health (pumping rate, pumping decline, and reproduction span). In the human HeLa cell model, morusin and mulberrin inhibited the phosphorylation of p70S6K1, promoted autophagy, and slowed cell senescence. The molecular docking study showed that mulberrin and morusin bind to the same pocket of p70S6K1. Collectively, our findings open up a potential class of prenylated flavones performing their antiaging activity via nutrient-sensing pathways.

Prevalence of myopia and consistency evaluation of three myopia assessment methods among children and adolescents / 中国学校卫生

Objective@#To evaluate the prevalence and consistency of screening myopia, non-cycloplegic myopia and cycloplegic myopia in children and adolescents, and to provide references for exploring the factors affecting the consistency of different definition methods.@*Methods@#A total of 3 868 children and adolescents aged 6 to 17 years from seven schools were included in a school based cross sectional study in Shandong Province in September 2020. The prevalence of screening myopia, non cycloplegic refraction, and cycloplegic refraction at different ages and all children and adolescents were analyzed. With cycloplegic spherical equivalent ≤-0.50 D as the gold standard for myopia, and Kappa test and area under the ROC curve were used to evaluate the consistency.@*Results@#The prevalence of cycloplegic myopia and screening myopia were 36.7% and 38.3% among children and adolescents. The prevalence of non cycloplegic myopia was 62.4%, which was significantly higher than screening myopia and cycloplegic myopia two methods in primary and junior high schools. Among 3 868 subjects, there were 3 628 (93.8%) subjects with screening myopia and 2 862 (74.0%) subjects with non cycloplegic myopia who were consistent with the gold standard for myopia. The Kappa values of screening myopia and non cycloplegic myopia were 0.87 and 0.51, and the area under the ROC curve was 0.94 (95% CI =0.93-0.95) and 0.79 (95% CI =0.78-0.81). Compared with other groups, children and adolescents aged 8 to 17 years, in junior or high school, urban residence, better presenting distance visual acuity, and astigmatism ≤1.50 D had a higher consistency in the application of screening myopia ( P <0.05).@*Conclusion@#The consistency between screening myopia and cycloplegic myopia is high, and the consistency between non cycloplegic objective myopia is low.

A mini-review on how the COVID-19 pandemic affected intertemporal choice.

The coronavirus disease (COVID-19) has extremely harmful effects on individual lifestyles, and at present, people must make financial or survival decisions under the profound changes frequently. Although it has been reported that COVID-19 changed decision-making patterns, the underlying mechanisms remained unclear. This mini-review focuses on the impact of the COVID-19 pandemic on intertemporal choice, and potential psychological, biological, and social factors that mediate this relationship. A search of the Web of Science electronic database yielded 23 studies. The results showed that under the COVID-19 pandemic, people tended to choose immediate and smaller rewards, and became less patient. In particular, people with negative emotions, in a worse condition of physical health, or who did not comply with their government restriction rules tended to become more "short-sighted" in behavioral terms. Future studies should examine more longitudinal and cross-cultural research to give a broad view about the decision-making change under the COVID-19 pandemic.

Prevalence of anisometropia and associated factors in Shandong school-aged children.

Objective: To investigate anisometropia's prevalence and associated factors in school-aged children. Methods: A cross-sectional school-based study was conducted in Shandong Province, China, including children aged 4 to 17 from 9 schools. Anisometropia was defined as the differences between the two eyes in spherical equivalent (SE) or cylinder degree of 1.00 diopter (D) or more [SE or cylindrical (CYL) difference ≥ 1.00 D] after cycloplegic autorefraction. The Generalized Linear Model (GLM) was used to analyze the effects of ocular parameters [the differences between eyes in axial length (AL), habitual visual acuity (HVA), and corneal astigmatism (CA)] and lifestyle parameters (time spent indoor near work and outdoor activities) on anisometropia. Results: Total 4,198 (93.4%) of the 4,494 children were included in the statistical analysis. The mean difference in inter-eye SE was 0.42 ± 0.61 D. The prevalence of anisometropia was 13.2% (95%CI: 12.1 to 14.2%) (SE anisometropia's prevalence:10.3%; CYL anisometropia's prevalence: 4.1%), increased with older age (OR = 1.10, P = 0.002), the worse myopic eye (myopia vs. premyopia, OR = 1.87, P = 0.002), the worse hyperopic eye (hyperopia vs. premyopia, OR = 1.77, P = 0.013), larger difference in inter-eye AL (0.1-0.3 vs. ≤ 0.1, OR = 1.67, P = 0.008; >0.3 vs. ≤ 0.1, OR = 28.61, P < 0.001), HVA (>0.2 vs. ≤ 0.2, OR = 3.01, P < 0.001), CA (OR = 6.24, P < 0.001), the worse stereoacuity (>100 vs. ≤ 100, OR = 1.59, P = 0.001), longer indoor near work time per day on weekends (4-8 vs. <4, OR = 1.41, P = 0.038; ≥8 vs. <4, OR = 1.40, P = 0.131), and shorter outdoor activity time per day on weekdays (≥1 vs. <1, OR = 0.75, P = 0.046) in multivariable analysis. In the SE anisometropia group, the difference in inter-eye AL (>0.3 vs. ≤ 0.1, ß: 0.556, 95%CI: 0.050 to 1.063), HVA (>0.2 vs. ≤ 0.2, ß: 0.511, 95%CI: 0.312 to 0.710), and CA (ß: 0.488, 95%CI: 0.289 to 0.688), stereoacuity (>100 vs. ≤ 100, ß: 0.299, 95%CI: 0.110 to 0.488) had a positive impact on the difference in inter-eye SE. Conclusions: Ocular parameters and lifestyle parameters are associated with the occurrence of anisometropia in children aged 4 to 17 years, including the difference in inter-eye AL, HVA, CA, stereoacuity, indoor near work time, and outdoor activity time. Preventing myopia and early treating anisometropic amblyopia may be effective ways to reduce the prevalence of anisometropia.

Mild mitochondrial impairment enhances innate immunity and longevity through ATFS-1 and p38 signaling.

While mitochondrial function is essential for life in all multicellular organisms, a mild impairment of mitochondrial function can extend longevity in model organisms. By understanding the molecular mechanisms involved, these pathways might be targeted to promote healthy aging. In studying two long-lived mitochondrial mutants in C. elegans, we found that disrupting subunits of the mitochondrial electron transport chain results in upregulation of genes involved in innate immunity, which is driven by the mitochondrial unfolded protein response (mitoUPR) but also dependent on the canonical p38-mediated innate immune signaling pathway. Both of these pathways are required for the increased resistance to bacterial pathogens and extended longevity of the long-lived mitochondrial mutants, as is the FOXO transcription factor DAF-16. This work demonstrates that both the p38-mediated innate immune signaling pathway and the mitoUPR act in concert on the same innate immunity genes to promote pathogen resistance and longevity and that input from the mitochondria can extend longevity by signaling through these pathways. This indicates that multiple evolutionarily conserved genetic pathways controlling innate immunity also function to modulate lifespan.

Global profiling of distinct cysteine redox forms reveals wide-ranging redox regulation in C. elegans.

Post-translational changes in the redox state of cysteine residues can rapidly and reversibly alter protein functions, thereby modulating biological processes. The nematode C. elegans is an ideal model organism for studying cysteine-mediated redox signaling at a network level. Here we present a comprehensive, quantitative, and site-specific profile of the intrinsic reactivity of the cysteinome in wild-type C. elegans. We also describe a global characterization of the C. elegans redoxome in which we measured changes in three major cysteine redox forms after H2O2 treatment. Our data revealed redox-sensitive events in translation, growth signaling, and stress response pathways, and identified redox-regulated cysteines that are important for signaling through the p38 MAP kinase (MAPK) pathway. Our in-depth proteomic dataset provides a molecular basis for understanding redox signaling in vivo, and will serve as a valuable and rich resource for the field of redox biology.

Neuronal SKN-1B modulates nutritional signalling pathways and mitochondrial networks to control satiety.

The feeling of hunger or satiety results from integration of the sensory nervous system with other physiological and metabolic cues. This regulates food intake, maintains homeostasis and prevents disease. In C. elegans, chemosensory neurons sense food and relay information to the rest of the animal via hormones to control food-related behaviour and physiology. Here we identify a new component of this system, SKN-1B which acts as a central food-responsive node, ultimately controlling satiety and metabolic homeostasis. SKN-1B, an ortholog of mammalian NF-E2 related transcription factors (Nrfs), has previously been implicated with metabolism, respiration and the increased lifespan incurred by dietary restriction. Here we show that SKN-1B acts in two hypothalamus-like ASI neurons to sense food, communicate nutritional status to the organism, and control satiety and exploratory behaviours. This is achieved by SKN-1B modulating endocrine signalling pathways (IIS and TGF-ß), and by promoting a robust mitochondrial network. Our data suggest a food-sensing and satiety role for mammalian Nrf proteins.

TOR Signaling in Caenorhabditis elegans Development, Metabolism, and Aging.

The Target of Rapamycin (TOR or mTOR) is a serine/threonine kinase that regulates growth, development, and behaviors by modulating protein synthesis, autophagy, and multiple other cellular processes in response to changes in nutrients and other cues. Over recent years, TOR has been studied intensively in mammalian cell culture and genetic systems because of its importance in growth, metabolism, cancer, and aging. Through its advantages for unbiased, and high-throughput, genetic and in vivo studies, Caenorhabditis elegans has made major contributions to our understanding of TOR biology. Genetic analyses in the worm have revealed unexpected aspects of TOR functions and regulation, and have the potential to further expand our understanding of how growth and metabolic regulation influence development. In the aging field, C. elegans has played a leading role in revealing the promise of TOR inhibition as a strategy for extending life span, and identifying mechanisms that function upstream and downstream of TOR to influence aging. Here, we review the state of the TOR field in C. elegans, and focus on what we have learned about its functions in development, metabolism, and aging. We discuss knowledge gaps, including the potential pitfalls in translating findings back and forth across organisms, but also describe how TOR is important for C. elegans biology, and how C. elegans work has developed paradigms of great importance for the broader TOR field.

Dietary Restriction Extends Lifespan through Metabolic Regulation of Innate Immunity.

Chronic inflammation predisposes to aging-associated disease, but it is unknown whether immunity regulation might be important for extending healthy lifespan. Here we show that in C. elegans, dietary restriction (DR) extends lifespan by modulating a conserved innate immunity pathway that is regulated by p38 signaling and the transcription factor ATF-7. Longevity from DR depends upon p38-ATF-7 immunity being intact but downregulated to a basal level. p38-ATF-7 immunity accelerates aging when hyperactive, influences lifespan independently of pathogen exposure, and is activated by nutrients independently of mTORC1, a major DR mediator. Longevity from reduced insulin/IGF-1 signaling (rIIS) also involves p38-ATF-7 downregulation, with signals from DAF-16/FOXO reducing food intake. We conclude that p38-ATF-7 is an immunometabolic pathway that senses bacterial and nutrient signals, that immunity modulation is critical for DR, and that DAF-16/FOXO couples appetite to growth regulation. These conserved mechanisms may influence aging in more complex organisms.

Mitochondrial unfolded protein response transcription factor ATFS-1 promotes longevity in a long-lived mitochondrial mutant through activation of stress response pathways.

BACKGROUND: The mitochondrial unfolded protein response (mitoUPR) is a stress response pathway activated by disruption of proteostasis in the mitochondria. This pathway has been proposed to influence lifespan, with studies suggesting that mitoUPR activation has complex effects on longevity. RESULTS: Here, we examined the contribution of the mitoUPR to the survival and lifespan of three long-lived mitochondrial mutants in Caenorhabditis elegans by modulating the levels of ATFS-1, the central transcription factor that mediates the mitoUPR. We found that clk-1, isp-1, and nuo-6 worms all exhibit an ATFS-1-dependent activation of the mitoUPR. While loss of atfs-1 during adulthood does not affect lifespan in any of these strains, absence of atfs-1 during development prevents clk-1 and isp-1 worms from reaching adulthood and reduces the lifespan of nuo-6 mutants. Examining the mechanism by which deletion of atfs-1 reverts nuo-6 lifespan to wild-type, we find that many of the transcriptional changes present in nuo-6 worms are mediated by ATFS-1. Genes exhibiting an ATFS-1-dependent upregulation in nuo-6 worms are enriched for transcripts that function in stress response and metabolism. Consistent, with this finding, loss of atfs-1 abolishes the enhanced stress resistance observed in nuo-6 mutants and prevents upregulation of multiple stress response pathways including the HIF-1-mediated hypoxia response, SKN-1-mediated oxidative stress response and DAF-16-mediated stress response. CONCLUSIONS: Our results suggest that in the long-lived mitochondrial mutant nuo-6 activation of the mitoUPR causes atfs-1-dependent changes in the expression of genes involved in stress response and metabolism, which contributes to the extended longevity observed in this mutant. This work demonstrates that the mitoUPR can modulate multiple stress response pathways and suggests that it is crucial for the development and lifespan of long-lived mitochondrial mutants.

Tanshinones extend chronological lifespan in budding yeast Saccharomyces cerevisiae.

Natural products with anti-aging property have drawn great attention recently but examples of such compounds are exceedingly scarce. By applying a high-throughput assay based on yeast chronological lifespan measurement, we screened the anti-aging activity of 144 botanical materials and found that dried roots of Salvia miltiorrhiza Bunge have significant anti-aging activity. Tanshinones isolated from the plant including cryptotanshione, tanshinone I, and tanshinone IIa, are the active components. Among them, cryptotanshinone can greatly extend the budding yeast Saccharomyces cerevisiae chronological lifespan (up to 2.5 times) in a dose- and the-time-of-addition-dependent manner at nanomolar concentrations without disruption of cell growth. We demonstrate that cryptotanshinone prolong chronological lifespan via a nutrient-dependent regime, especially essential amino acid sensing, and three conserved protein kinases Tor1, Sch9, and Gcn2 are required for cryptotanshinone-induced lifespan extension. In addition, cryptotanshinone significantly increases the lifespan of SOD2-deleted mutants. Altogether, those data suggest that cryptotanshinone might be involved in the regulation of, Tor1, Sch9, Gcn2, and Sod2, these highly conserved longevity proteins modulated by nutrients from yeast to humans.