[Exploring implementation strategies for healthy longevity among the elderly population in China based on the delphi method].

Objective: To explore the implementation strategies for promoting healthy longevity among the elderly population in China based on the Delphi method. Methods: Through literature review and expert discussion, a framework for implementation strategies to achieve healthy longevity among the elderly was determined, and a preliminary checklist of implementation strategies was developed. The Delphi method was employed from August to December 2022, inviting 25 experts from various disciplines such as clinical medicine, public health, basic research, and the elderly care services industry. Experts were sent consultation questionnaires via email to assess the importance, feasibility, judgment basis and familiarity of each implementation strategy. Active coefficient, authority coefficient, and harmony coefficient were analyzed to ultimately determine the important and feasible implementation strategies for healthy longevity that were suitable for the Chinese elderly population. Results: The expert active coefficients of the two rounds were 96.00% (24/25) and 79.17% (19/24). The authority coefficients were (0.76±0.19) and (0.77±0.17). The average scores of importance were (4.32±0.84) and (4.36±0.82), and the corresponding scores of feasibility were (3.72±1.04) and (3.80±0.92). The harmony coefficients for the importance score were 0.269 (χ2=594.084, P<0.001) and 0.159 (χ2=193.624, P<0.001). The harmony coefficients for feasibility scores were 0.205 (χ2=452.008, P<0.001) and 0.167 (χ2=202.878, P<0.001). The final eight implementation strategies were identified after two rounds of consultation. Conclusion: Through two rounds of Delphi consultations, eight important and feasible implementation strategies for promoting healthy longevity that are suitable for the Chinese context have been proposed.

Effect of temperature on the biological parameters of pink bollworm, Pectinophora gossypiella Saunders (Lepidoptera: Gelechiidae).

Pink bollworm (PBW) Pectinophora gossypiella is an important pest cotton worldwide. There are multiple factors which determines the occurrence and distribution of P. gossypiella across different cotton growing regions of the world, and one such key factor is 'temperature'. The aim was to analyze the life history traits of PBW across varying temperature conditions. We systematically explored the biological and demographic parameters of P. gossypiella at five distinct temperatures; 20, 25, 30, 35 and 40 ± 1 °C maintaining a photoperiod of LD 16:8 h. The results revealed that the total developmental period of PBW shortens with rising temperatures, and the highest larval survival rates were observed between 30 °C and 35 °C, reaching 86.66% and 80.67%, respectively. Moreover, significant impacts were observed as the pupal weight, percent mating success, and fecundity exhibited higher values at 30 °C and 35 °C. Conversely, percent egg hatching, larval survival, and adult emergence were notably lower at 20 °C and 40 °C, respectively. Adult longevity decreased with rising temperatures, with females outliving males across all treatments. Notably, thermal stress had a persistent effect on the F1 generation, significantly affecting immature stages (egg and larvae), while its impact on reproductive potential was minimal. These findings offer valuable insights for predicting the population dynamics of P. gossypiella at the field level and developing climate-resilient management strategies in cotton.

Leach's storm-petrel (Hydrobates leucorhous), a long-lived seabird shows flexible, condition-dependent, feeding strategies in response to poor chick condition.

BACKGROUND: Parent-offspring conflict represents the sensitive balance of resource allocation between self-maintenance and reproduction. Two strategies have been proposed to better understand how species manage this conflict. In fixed-level feeding behavior, parents feed offspring consistent quantities of food; while flexible feeding shows plasticity in parental allocation based on offspring need. Life-history theory predicts that parents of long-lived species prioritize their survival and may favor the fixed-level hypothesis to maximize lifetime reproductive success. In this study, we highlight the natural variation of parent-offspring allocation strategies within a unique population of Leach's storm-petrels (Hydrobates leucorhous), and through month-long food supplementation and restriction manipulations, we investigate how chick condition affects parental provisioning during the chick-rearing period of reproduction. RESULTS: We show that the parents upregulated chick feeding frequency of nutritionally deprived chicks, resulting in a larger total amount of food delivered during the study period. Additionally, the proportion of nights when both parents fed was highest in restricted chicks, and the proportion of nights when neither parents fed was lowest in restricted chicks, suggesting that storm-petrel parents shorten their foraging bouts to deliver food more often when their chicks are in relatively poor condition. CONCLUSIONS: Our results support that Leach's storm-petrels use a flexible-level feeding strategy, suggesting that parents can assess offspring condition, and respond by feeding chicks at higher frequencies. These data provide insight on how a long-lived seabird balances its own energetic demands with that of their offspring during the reproductive period.

Durable proteins appear to protect ovaries.

Studies find long-lived proteins are prevalent in the organs.

An expedited screening platform for the discovery of anti-ageing compounds in vitro and in vivo.

BACKGROUND: Restraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great interest in anti-ageing drug discovery. However, this currently requires laborious and lengthy longevity analysis. Here, we present a novel screening readout for the expedited discovery of compounds that restrain ageing of cell populations in vitro and enable extension of in vivo lifespan. METHODS: Using Illumina methylation arrays, we monitored DNA methylation changes accompanying long-term passaging of adult primary human cells in culture. This enabled us to develop, test, and validate the CellPopAge Clock, an epigenetic clock with underlying algorithm, unique among existing epigenetic clocks for its design to detect anti-ageing compounds in vitro. Additionally, we measured markers of senescence and performed longevity experiments in vivo in Drosophila, to further validate our approach to discover novel anti-ageing compounds. Finally, we bench mark our epigenetic clock with other available epigenetic clocks to consolidate its usefulness and specialisation for primary cells in culture. RESULTS: We developed a novel epigenetic clock, the CellPopAge Clock, to accurately monitor the age of a population of adult human primary cells. We find that the CellPopAge Clock can detect decelerated passage-based ageing of human primary cells treated with rapamycin or trametinib, well-established longevity drugs. We then utilise the CellPopAge Clock as a screening tool for the identification of compounds which decelerate ageing of cell populations, uncovering novel anti-ageing drugs, torin2 and dactolisib (BEZ-235). We demonstrate that delayed epigenetic ageing in human primary cells treated with anti-ageing compounds is accompanied by a reduction in senescence and ageing biomarkers. Finally, we extend our screening platform in vivo by taking advantage of a specially formulated holidic medium for increased drug bioavailability in Drosophila. We show that the novel anti-ageing drugs, torin2 and dactolisib (BEZ-235), increase longevity in vivo. CONCLUSIONS: Our method expands the scope of CpG methylation profiling to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro, and in vivo, providing a novel accelerated discovery platform to test sought after anti-ageing compounds and geroprotectors.

Improving bee feed recipes to safeguard honeybee colonies during times of food scarcity.

In beekeeping, when natural nectar or pollen sources become limited, it is crucial to provide supplemental bee feed to maintain the viability of the bee colony. This study was conducted during the autumn food shortage season, during which bees were fed with different proportions of modified bee feed. We identified an optimal bee diet by evaluating honeybee longevity, food consumption, body weight, and gut microbe distribution, with natural pollen serving as a control diet. The results indicated that bees preferred a mixture of 65% defatted soy flour, 20% corn protein powder, 13% wheat germ flour, 2% yeast powder, and a 50% sucrose solution. This bee food recipe significantly increased the longevity, feed consumption, and body weight of bees. The group fed the natural pollen diet exhibited a greater abundance of essential intestinal bacteria. The bee diets used in this study contained higher protein levels and lower concentrations of unsaturated fatty acids and vitamins than did the diets stored within the colonies. Therefore, we propose that incorporating both bee feed and natural pollen in beekeeping practices will achieve more balanced nutritional intake.

Microplastic exposure disturbs sleep structure, reduces lifespan, and decreases ovary size in Drosophila melanogaster.

The organ-specific toxicity resulting from microplastic (MP) exposure has been extensively explored, particularly concerning the gut, liver, testis, and lung. However, under natural conditions, these effects are not restricted to specific organs or tissues. Investigating whether MP exposure presents a systemic threat to an entire organism, impacting factors such as lifespan, sleep, and fecundity, is essential. In this study, we investigated the effects of dietary exposure to two different doses of MPs (1-5 µm) using the terrestrial model organism Drosophila melanogaster. Results indicated that the particles caused gut damage and remained within the digestive system. Continuous MP exposure significantly shortened the lifespan of adult flies. Even short-term exposure disrupted sleep patterns, increasing the length of daytime sleep episodes. Additionally, one week of MP exposure reduced ovary size, with a trend towards decreased egg-laying in mated females. Although MPs did not penetrate the brain or ovaries, transcriptome analysis revealed altered gene expression in these tissues. In the ovary, Gene Ontology (GO) analysis indicated genotoxic effects impacting inflammation, circadian regulation, and metabolic processes, with significant impacts on extracellular structure-related pathways. In the brain, GO analysis identified changes in pathways associated with proteolysis and carbohydrate metabolism. Overall, this study provides compelling evidence of the systemic negative effects of MP exposure, highlighting the urgent need to address and mitigate environmental MP pollution.

Should patients with exceptional longevity be treated for osteoporosis after a hip fracture?

BACKGROUND: There are no studies focusing on treatment for osteoporosis in patients with exceptional longevity after suffering a hip fracture. OBJECTIVE: To assess the advisability of initiating treatment for osteoporosis after a hip fracture according to the incidence of new fragility fractures after discharge, risk factors for mortality and long-term survival. DESIGN: Retrospective review. SETTING: A tertiary university hospital serving a population of ~425 000 inhabitants in Barcelona. SUBJECTS: All patients >95 years old admitted with a fragility hip fracture between December 2009 and September 2015 who survived admission were analysed until the present time. METHODS: Pre-fracture ambulation ability and new fragility fractures after discharge were recorded. Risk factors for 1-year and all post-discharge mortality were calculated with multivariate Cox regression. Kaplan-Meier survival curve analyses were performed. RESULTS: One hundred and seventy-five patients were included. Median survival time was 1.32 years [95% confidence interval (CI) 1.065-1.834], with a maximum of 9.2 years. Male sex [hazard ratio (HR) 2.488, 95% CI 1.420-4.358] and worse previous ability to ambulate (HR 2.291, 95% CI 1.417-3.703) were predictors of mortality. After discharge and up to death or the present time, 10 (5.7%) patients had a new fragility fracture, half of them during the first 6 months. CONCLUSIONS: Few new fragility fractures occurred after discharge and half of these took place in the first 6 months. The decision to start treatment of osteoporosis should be individualised, bearing in mind that women and patients with better previous ambulation ability will have a better chance of survival.

Behavioral Dysfunctions Caused by Pyridoxamine Deficiency in Drosophila melanogaster.

Pyridoxamine (PM) is one of the natural vitamins B6 (VB6) and functions as an endogenous inhibitor for the formation of AGEs (advanced glycation end products). The AGEs are implicated in aging, diabetes, and various neuropsychiatric disease, including schizophrenia, Alzheimer's disease, and Parkinson's disease. However, it is unclear whether the absence of PM per se accumulates AGEs in vivo and causes behavioral dysfunctions. To address these points, we raised PM-deficient fruit flies, Drosophila melanogaster, with the sterilized defined medium. Flies reared in a PM-deficient medium accumulated AGEs and reduced lifespan, impaired gustatory response, sleep, courtship behavior, and olfactory learning. These results suggest that PM suppresses AGE accumulation in vivo and is required for regulating innate and empirical behaviors.

Lack of T04C9.1, the Homologue of Mammalian APPL2, Leads to Premature Ageing and Shortens Lifespan in Caenorhabditis elegans.

Ageing has been identified as an independent risk factor for various diseases; however, the physiological basis and molecular changes related to ageing are still largely unknown. Here, we show that the level of APPL2, an adaptor protein, is significantly reduced in the major organs of aged mice. Knocking down APPL2 causes premature ageing of human umbilical vein endothelial cells (HUVECs). We find that a lack of T04C9.1, the homologue of mammalian APPL2, leads to premature ageing, slow movements, lipid deposition, decreased resistance to stresses, and shortened lifespan in Caenorhabditis elegans (C. elegans), which are associated with decreased autophagy. Activating autophagy by rapamycin or inhibition of let-363 suppresses the age-related alternations, impaired motility, and shortened lifespan of C. elegans, which are reversed by knocking down autophagy-related genes. Our work provides evidence that APPL2 and its C. elegans homologue T04C9.1 decrease with age and reveals that a lack of T04C9.1 bridges autophagy decline and ageing in C. elegans.

Relationship between Hypoxia and Hypercapnia Tolerance and Life Expectancy.

The review discusses the potential relationship between hypoxia resistance and longevity, the influence of carbon dioxide on the mechanisms of aging of the mammalian organism, and intermittent hypercapnic-hypoxic effects on the signaling pathways of aging mechanisms. In the article, we focused on the potential mechanisms of the gero-protective efficacy of carbon dioxide when combined with hypoxia. The review summarizes the possible influence of intermittent hypoxia and hypercapnia on aging processes in the nervous system. We considered the perspective variants of the application of hypercapnic-hypoxic influences for achieving active longevity and the prospects for the possibilities of developing hypercapnic-hypoxic training methods.

EGCG Alleviates the Aging Toxicity Induced by 3-MCPD via IIS Pathway in Caenorhabditis elegans with Abnormal Reproduction and Heat Shock Protein.

This study aimed to investigate the mitigation effect of epigallocatechin gallate (EGCG) on aging induced by 3-monochloropropane-1,2-diol (3-MCPD) in Caenorhabditis elegans, evaluate health indicators during the process, and reveal the underlying mechanism through transcriptomics and identification of mutants. The results showed that EGCG alleviated the declined fertility, shortened lifespan, reduced body size, weakened movement, increased reactive oxygen species and lipofuscin, and damaged antioxidative stress response and excessive heat shock proteins caused by 3-MCPD. Transcriptomics study indicated that treatment with 3-MCPD and EGCG altered gene expression, and gene mutants confirmed the involvement of insulin/IGF-1 signaling pathway in mediating the process that EGCG alleviated the aging toxicity induced by 3-MCPD. The study showed that EGCG alleviated the aging toxicity induced by 3-MCPD.

Inhibition of a cyclic nucleotide-gated channel on neuronal cilia activates unfolded protein response in intestinal cells to promote longevity.

Ciliary defects are linked to ciliopathies, but impairments in the sensory cilia of Caenorhabditis elegans neurons extend lifespan, a phenomenon with previously unclear mechanisms. Our study reveals that neuronal cilia defects trigger the unfolded protein response of the endoplasmic reticulum (UPRER) within intestinal cells, a process dependent on the insulin/insulin-like growth factor 1 (IGF-1) signaling transcription factor and the release of neuronal signaling molecules. While inhibiting UPRER doesn't alter the lifespan of wild-type worms, it normalizes the extended lifespan of ciliary mutants. Notably, deactivating the cyclic nucleotide-gated (CNG) channel TAX-4 on the ciliary membrane promotes lifespan extension through a UPRER-dependent mechanism. Conversely, constitutive activation of TAX-4 attenuates intestinal UPRER in ciliary mutants. Administering a CNG channel blocker to worm larvae activates intestinal UPRER and increases adult longevity. These findings suggest that ciliary dysfunction in sensory neurons triggers intestinal UPRER, contributing to lifespan extension and implying that transiently inhibiting ciliary channel activity may effectively prolong lifespan.

Maternal care leads to the evolution of long, slow lives.

Animals, and mammals in particular, vary widely in their "pace of life," with some species living long lives and reproducing infrequently (slow life histories) and others living short lives and reproducing often (fast life histories). These species also vary in the importance of maternal care in offspring fitness: In some species, offspring are fully independent of their mothers following a brief period of nutritional input, while others display a long period of continued dependence on mothers well after nutritional dependence. Here, we hypothesize that these two axes of variation are causally related to each other, such that extended dependence of offspring on maternal presence leads to the evolution of longer lives at the expense of reproduction. We use a combination of deterministic modeling and stochastic agent-based modeling to explore how empirically observed links between maternal survival and offspring fitness are likely to shape the evolution of mortality and fertility. Each of our modeling approaches leads to the same conclusion: When maternal survival has a strong impact on the survival of offspring and grandoffspring, populations evolve longer lives with less frequent reproduction. Our results suggest that the slow life histories of humans and other primates as well as other long-lived, highly social animals such as hyenas, whales, and elephants are partially the result of the strong maternal care that these animals display. We have designed our models to be readily parameterized with demographic data that are routinely collected by long-term researchers, which will facilitate more thorough testing of our hypothesis.

Biomarkers for aging in Caenorhabditis elegans high throughput screening.

Aging is characterized by a functional decline in organism fitness over time due to a complex combination of genetic and environmental factors [ 1-4]. With an increasing elderly population at risk of age-associated diseases, there is a pressing need for research dedicated to promoting health and longevity through anti-aging interventions. The roundworm Caenorhabditis elegans is an established model organism for aging studies due to its short life cycle, ease of culture, and conserved aging pathways. These benefits also make the worm well-suited for high-throughput screening (HTS) methods to study biomarkers of the molecular changes, cellular dysfunction, and physiological decline associated with aging. Within this review, we offer a summary of recent advances in HTS techniques to study biomarkers of aging in C. elegans.

Jujubae Fructus extract prolongs lifespan and improves stress tolerance in Caenorhabditis elegans dependent on DAF-16/SOD-3.

Jujubae Fructus, the fruit of Ziziphus jujuba Mill has been used as one of the medicine food homology species for thousands of years in China. Studies have shown that the active ingredients of Jujubae Fructus have a variety of biological effects, but its role in the aging process still lacks knowledge. Here, we investigated the effect of Jujubae Fructus extract (JE) on Caenorhabditis elegans lifespan and its potential mechanism. The lifespan of C. elegans treated with JE was signifificantly increased in a dose-dependent manner. In addition, JE treatment prolonged the reproductive period and increased normal activity during aging in C. elegans. Similarly, JE supplementation also enhanced the resistance to heat and oxidative stress in C. elegans. Furthermore, the mutant worms' lifespan assays demonstrated that JE requires daf-16 to prolong lifespan. DAF-16::GFP analysis of TJ356 showed that JE treatment translocates DAF-16::GFP to nucleus in transgenic worms. By analyzing the downstream of daf-16, we identify that JE may regulate sod3 downstream of daf-16. Mutant worms' lifespan and transgenic reporter gene expression assays revealed that increasing SOD-3 expression was critical for extending longevity in C. elegans with JE therapy. Collectively, these data indicate that JE may have an important role in C. elegans longevity that is dependent on DAF-16 and SOD-3.

Dietary sucrose determines the regulatory activity of lithium on gene expression and lifespan in Drosophila melanogaster.

The amount of dietary sugars and the administration of lithium both impact the lifespan of the fruit fly Drosophila melanogaster. It is noteworthy that lithium is attributed with insulin-like activity as it stimulates protein kinase B/Akt and suppresses the activity of glycogen synthase kinase-3 (GSK-3). However, its interaction with dietary sugar has largely remained unexplored. Therefore, we investigated the effects of lithium supplementation on known lithium-sensitive parameters in fruit flies, such as lifespan, body composition, GSK-3 phosphorylation, and the transcriptome, while varying the dietary sugar concentration. For all these parameters, we observed that the efficacy of lithium was significantly influenced by the sucrose content in the diet. Overall, we found that lithium was most effective in enhancing longevity and altering body composition when added to a low-sucrose diet. Whole-body RNA sequencing revealed a remarkably similar transcriptional response when either increasing dietary sucrose from 1% to 10% or adding 1 mM LiCl to a 1% sucrose diet, characterized by a substantial overlap of nearly 500 differentially expressed genes. Hence, dietary sugar supply is suggested as a key factor in understanding lithium bioactivity, which could hold relevance for its therapeutic applications.

Effects of miR-306 Perturbation on Life Parameters in the English Grain Aphid, Sitobion avenae (Homoptera: Aphididae).

MicroRNAs (miRNA) play a vital role in insects' growth and development and have significant potential value in pest control. Previously, we identified miR-306 from small RNA libraries within the English grain aphid, Sitobion avenae, a devasting insect pest for wheat. miR-306 not only involves in wing morphogenesis, but also is critically important for aphid survival. Its specific impacts on the life history traits, however, remain unclear. Here, we evaluate the impact of miR-306 perturbation on S. avenae populations using a two-sex life table approach. This comprehensive analysis revealed that miR-306 perturbation significantly prolongs the developmental stages (9.64% and 8.20%) and adult longevity of S. avenae, while decreasing pre-adult survival rate (41.45% and 38.74%) and slightly reducing average fecundity (5.80% and 13.05%). Overall, miR-306 perturbation negatively affects the life table parameters of the aphid population. The population prediction models show a significant decline in the aphid population 60 days post interference, compared to the control groups (98.14% and 97.76%). Our findings highlight the detrimental effects of miR-306 perturbation on S. avenae population growth and suggest potential candidate genes for the development of RNAi-based biopesticides targeted specifically at this pest species.

Long live the RNAs: The guardians of neuronal longevity?

In a recent publication in Science, Zocher et al.1 identify and characterize long-lived nuclear RNA in the mouse brain, suggesting their potential roles as guardians of neuronal longevity.