[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.

Activity of DNA Repair Systems in the Cells of Long-Lived Rodents and Bats.

Damages of various origin accumulated in the genomic DNA can lead to the breach of genome stability, and are considered to be one of the main factors involved in cellular senescence. DNA repair systems in mammalian cells ensure effective damage removal and repair of the genome structure, therefore, activity of these systems is expected to be correlated with high maximum lifespan observed in the long-lived mammals. This review discusses current results of the studies focused on determination of the DNA repair system activity and investigation of the properties of its key regulatory proteins in the cells of long-lived rodents and bats. Based on the works discussed in the review, it could be concluded that the long-lived rodents and bats in general demonstrate high efficiency in functioning and regulation of DNA repair systems. Nevertheless, a number of questions around the study of DNA repair in the cells of long-lived rodents and bats remain poorly understood, answers to which could open up new avenues for further research.

Life history of the two predacious mites species, Amblyseius swirskii, and Neoseiulus cucumeris (Acari: Phytoseiidae), as biological control agents of the date palm mite, Oligonychus afrasiaticus (Acari: Tetranychidae).

The date palm mite, Oligonychus afrasiaticus (McGregor) (Acari: Tetranychidae), is a serious pest of dates in the Middle East and North Africa, inflicting severe economic damage if not controlled early. As predaceous mites are known to be potential biocontrol agents against several pests, so predation capacity, life table, reproduction, and survival of Amblyseius swirskii Athias-Henriot and Neoseiulus cucumeris (Oudemans) (Acari: Phytoseiidae), collected from date palm farms in Qassim Saudi Arabia, were studied under laboratory conditions (25 °C, 30 °C, 35 °C and 50 ± 5% RH) against all motile stages of O. afrasiaticus. For both predators, mean developmental time, oviposition period, and longevity were inversely related to temperature from 25 to 35 °C. Various parameters were studied for A. swirskii and N. cucumeris at 25 °C, 30 °C and 35 °C, i.e. the female developmental time, 9.37, 7.29, 5.56, and 10.67, 8.38, 6.45 d; oviposition period, 19.77, 16.18, 13.94 and 15.90, 13.84, 10.64 d; longevity, 29.39, 24.79, 20.64 and 25.42, 21.94, 17.39 d; fecundity, 31.91, 37.10, 42.16 and 21.75, 26.84, 30.56 eggs per female, respectively. The maximum daily predation rate for both the predators was recorded at 35 °C during the oviposition period. The total predation of A. swirskii and N. cucumeris female was 370.86, 387.54, 405.83, 232.14, 263.32, 248.85 preys at 25 °C, 30 °C and 35 °C respectively. The maximum reproduction rate of A. swirskii and N. cucumeris (3.02, 2.87 eggs/♀/day) was recorded at 35 °C while the minimum (2.00, 1.36 eggs/♀/day) was recorded at 25 °C. The life table parameters were estimated as net reproductive rate (Ro) 21.68, 25.94, 29.52 and 18.95, 20.25, 22.78; the mean generation time (T) 24.92, 21.82, 18.24 and 26.30, 23.60, 20.56 d; the intrinsic rate of increase (rm) 0.181, 0.232, 0.248 and 0.170, 0.185, 0.196; the finite rate of increase (λ) 1.365, 1.551, 1.706 and 1.126, 1.324, 1.428 for A. swirskii and N. cucumeris at 25 °C, 30 °C and 35 °C respectively. The results of this study suggested that the two phytoseiid species are promising biological control agents of O. afrasiaticus at a wide range of temperatures.

A Seed Storage Protocol to Determine Longevity.

The longevity of seeds, also known as storability, is the period of time for which a seed lot maintains its viability during storage. The method aims to determine longevity of a seed lot during storage in a controlled environment. Seeds are first rehydrated to a preset water content (or relative humidity, RH) and then incubated under controlled conditions for various periods of time to allow for deterioration to occur. At increasing intervals during storage, seeds are retrieved and viability is tested by scoring germination of the seed lot (i.e., radicle protrusion). From these data, a survival curve can be drawn depicting loss of germination during time of storage from which different parameters estimating longevity can be inferred. These parameters can be used to compare longevity between different seed lots, genotypes, or species at similar storage conditions. This test can also be used as a proxy to measure seed vigor or physiological seed quality.

Trends in socioeconomic inequalities in life expectancy and lifespan variation in Chile.

Background: Socioeconomic disparities in life expectancy are well-documented in various contexts, including Chile. However, there is a lack of research examining trends in life expectancy inequalities and lifespan variation over time. Addressing these gaps can provide crucial insights into the dynamics of health inequalities. Methods: This study utilizes data from census records, population surveys, and death certificates to compare the life expectancy and the lifespan variation at age 26 of individuals according to their rank in the distribution of years of education within their own birth cohort. The analysis spans three periods (1991, 2002, and 2017) and focuses on two educational groups: individuals in the first (lowest) quintile and tenth (highest) decile of educational attainment. Changes in life expectancy are disaggregated by major causes of death to elucidate their contributions to overall trends. Results: Consistent with existing literature, our findings confirm that individuals with lower education levels experience lower life expectancy and higher lifespan variation compared to their more educated counterparts. Notably, by 2017, life expectancy for individuals in the lowest quintile of education has caught up with that of the top decile in 1991, albeit with contrasting trends between genders. Among women, the gap has reduced, while it has increased for males. Moreover, lifespan variation decreased (increased) over time for individuals in the tenth decile (first quintile). The leading causes of death that explain the increase in life expectancy in women and men in the tenth decile as well as women in the first quintile are cardiovascular, cancer, respiratory and digestive diseases. In the case of males in the first quintile, few gains have been made in life expectancy resulting from cancer and a negative contribution is associated with digestive conditions. Conclusions: This study underscores persistent socioeconomic disparities in life expectancy in Chile, emphasizing the importance of ongoing monitoring of health inequalities across different demographic segments. The gender-specific and educational gradient trends highlight areas for targeted interventions aimed at reducing health disparities and improving overall population health outcomes. Further research is warranted to delve into specific causes of death driving life expectancy differentials and to inform evidence-based policy interventions.

Conditional Inhibition of Eip75B Eliminates the Effects of Mating and Mifepristone on Lifespan in Female Drosophila.

Mating in female Drosophila melanogaster causes midgut hypertrophy and reduced lifespan, and these effects are blocked by the drug mifepristone. Eip75B is a transcription factor previously reported to have pleiotropic effects on Drosophila lifespan. Because Eip75B null mutations are lethal, conditional systems and/or partial knock-down are needed to study Eip75B effects in adults. Previous studies showed that Eip75B is required for adult midgut cell proliferation in response to mating. To test the possible role of Eip75B in mediating the lifespan effects of mating and mifepristone, a tripartite FLP-recombinase-based conditional system was employed that provides controls for genetic background. Expression of a Hsp70-FLP transgene was induced in third instar larvae by a brief heat pulse. The FLP recombinase catalyzed the recombination and activation of an Actin5C-GAL4 transgene. The GAL4 transcription factor in turn activated expression of a UAS-Eip75B-RNAi transgene. Inhibition of Eip75B activity was confirmed by loss of midgut hypertrophy upon mating, and the lifespan effects of both mating and mifepristone were eliminated. In addition, the negative effects of mifepristone on egg production were eliminated. The data indicate that Eip75B mediates the effects of mating and mifepristone on female midgut hypertrophy, egg production, and lifespan.

What factors preventing the older adults in China from living longer: a machine learning study.

BACKGROUND: The fact that most older people do not live long means that they do not have more time to pursue self-actualization and contribute value to society. Although there are many studies on the longevity of the elderly, the limitations of traditional statistics lack the good ability to study together the important influencing factors and build a simple and effective prediction model. METHODS: Based on the the data of Chinese Longitudinal Healthy Longevity Survey (CLHLS), 2008-2018 cohort and 2014-2018 cohort were selected and 16 features were filtered and integrated. Five machine learning algorithms, Elastic-Net Regression (ENR), Decision Tree (DT), Random Forest (RF), K-Nearest Neighbor (KNN), and eXtreme Gradient Boosting (XGBoost), were used to develop models and assessed by internal validation with CLHLS 2008-2018 cohort and temporal validation with CLHLS 2014-2018 cohort. Besides, the best performing model was explained and according to the variable importance results, simpler models would be developed. RESULTS: The results showed that the model developed by XGBoost algorithm had the best performance with AUC of 0.788 in internal validation and 0.806 in temporal validation. Instrumental activity of daily living (IADL), leisure activity, marital status, sex, activity of daily living (ADL), cognitive function, overall plant-based diet index (PDI) and psychological resilience, 8 features were more important in the model. Finally, with these 8 features simpler models were developed, it was found that the model performance did not decrease in both internal and temporal validation. CONCLUSIONS: The study indicated that the importance of these 8 factors for predicting the death of elderly people in China and built a simple machine learning model with good predictive performance. It can inspire future key research directions to promote longevity of the elderly, as well as in practical life to make the elderly healthy longevity, or timely end-of-life care for the elderly, and can use predictive model to aid decision-making.

Late-life dietary folate restriction reduces biosynthesis without compromising healthspan in mice.

Folate is a vitamin required for cell growth and is present in fortified foods in the form of folic acid to prevent congenital abnormalities. The impact of low-folate status on life-long health is poorly understood. We found that limiting folate levels with the folate antagonist methotrexate increased the lifespan of yeast and worms. We then restricted folate intake in aged mice and measured various health metrics, metabolites, and gene expression signatures. Limiting folate intake decreased anabolic biosynthetic processes in mice and enhanced metabolic plasticity. Despite reduced serum folate levels in mice with limited folic acid intake, these animals maintained their weight and adiposity late in life, and we did not observe adverse health outcomes. These results argue that the effectiveness of folate dietary interventions may vary depending on an individual's age and sex. A higher folate intake is advantageous during the early stages of life to support cell divisions needed for proper development. However, a lower folate intake later in life may result in healthier aging.

Timut Pepper Extract Slows Age-Dependent Decline of Mobility and Collagen Loss and Promotes Longevity.

Investigations into human longevity are increasingly focusing on healthspan enhancement, not just lifespan extension. Lifestyle modifications and nutritional choices, including food supplements, can significantly affect aging and general health. Phytochemicals in centenarians' diets, such as those found in Timut pepper, a Nepalese spice with various medicinal properties, may contribute to their longevity. Similarly, Sichuan pepper, a related species, has demonstrated anti-inflammatory and neuroprotective activities. With the broader purpose of uncovering a novel treatment to address aging and its comorbidities, this study aims to investigate the potential lifespan- and healthspan-promoting effects of Timut pepper using the model organism Caenorhabditis elegans. We show that Timut pepper extract extends C. elegans' lifespan at different maintenance temperatures and increases the proportion of active nematodes in their early adulthood. In addition, we show that Timut pepper extract enhances speed and distance moved as the nematodes age. Finally, Timut pepper extract assures extracellular matrix homeostasis by slowing the age-dependent decline of collagen expression.

Mutations in fibulin-1 and collagen IV suppress the short healthspan of mig-17/ADAMTS mutants in Caenorhabditis elegans.

The ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family metalloprotease MIG-17 plays a crucial role in the migration of gonadal distal tip cells (DTCs) in Caenorhabditis elegans. MIG-17 is secreted from the body wall muscle cells and localizes to the basement membranes (BMs) of various tissues including the gonadal BM where it regulates DTC migration through its catalytic activity. Missense mutations in the BM protein genes, let-2/collagen IV a2 and fbl-1/fibulin-1, have been identified as suppressors of the gonadal defects observed in mig-17 mutants. Genetic analyses indicate that LET-2 and FBL-1 act downstream of MIG-17 to regulate DTC migration. In addition to the control of DTC migration, MIG-17 also plays a role in healthspan, but not in lifespan. Here, we examined whether let-2 and fbl-1 alleles can suppress the age-related phenotypes of mig-17 mutants. let-2(k196) fully and fbl-1(k201) partly, but not let-2(k193) and fbl-1(k206), suppressed the senescence defects of mig-17. Interestingly, fbl-1(k206), but not fbl-1(k201) or let-2 alleles, exhibited an extended lifespan compared to the wild type when combined with mig-17. These results reveal allele specific interactions between let-2 or fbl-1 and mig-17 in age-related phenotypes, indicating that basement membrane physiology plays an important role in organismal aging.

Association of increased participation in social activity in later life with risk of all-cause mortality and heart diseases in older people: results from the Chinese Longitudinal Healthy Longevity Survey (CLHLS).

Background: Previous studies have shown social activity is associated with reduced risk of health outcomes. However, among older people (≥65 years) who were socially inactive at baseline, limited study explored whether increased participation in social activity in later life was associated with reduced risk of health outcomes; therefore, using the data from the Chinese Longitudinal Healthy Longevity Survey, the study was performed. Methods: The study outcomes were 10-year all-cause mortality (sample number = 9,984) and 10-year heart diseases (sample number = 7,496). The exposure was the change of social activity frequency. Cox regression analysis was used for data analysis. Results: During the follow-up, there were 6,407 all-cause mortalities and 1,035 heart diseases, respectively. Kaplan-Meier analysis demonstrated that cumulative incidences of all-cause mortality were significantly lower in participants with changes into more frequent social activity (log-rank p < 0.001), while no significant difference was observed for heart diseases (log-rank p = 0.330). Compared with the subgroup who never participated in social activity at baseline, adjusted HRs of all-cause mortality were 0.79 (95% CI: 0.70-0.90, p < 0.001), 0.78 (95% CI: 0.63-0.96, p = 0.019), 0.74 (0.59-0.92, p = 0.006), and 0.70 (95% CI: 0.56-0.88, p = 0.002) for the subgroup of switching to sometimes, the subgroup of switching to once a month, the subgroup of switching to once a week, and the subgroup of switching to everyday, respectively. The corresponding HRs of heart diseases were 0.83 (95% CI: 0.65-1.08, p = 0.170), 0.82 (95% CI: 0.51-1.31, p = 0.412), 0.91 (0.58-1.42, p = 0.675) and 0.75 (95% CI: 0.47-1.20, p = 0.227), respectively. Stratified and sensitivity analyses revealed similar results. Conclusion: Among older people who never participated in social activity, increased participation in social activity in later life was associated with reduced risk of all-cause mortality, but was not associated with reduced risk of heart diseases.

Lifespan differences in hippocampal subregion connectivity patterns during movie watching.

Age-related episodic memory decline is attributed to functional alternations in the hippocampus. Less clear is how aging affects the functional connections of the hippocampus to the rest of the brain during episodic memory processing. We examined fMRI data from the CamCAN dataset, in which a large cohort of participants watched a movie (N = 643; 18-88 years), a proxy for naturalistic episodic memory encoding. We examined connectivity profiles across the lifespan both within the hippocampus (anterior, posterior), and between the hippocampal subregions and cortical networks. Aging was associated with reductions in contralateral (left, right) but not ipsilateral (anterior, posterior) hippocampal subregion connectivity. Aging was primarily associated with increased coupling between the anterior hippocampus and regions affiliated with Control, Dorsal Attention and Default Mode networks, yet decreased coupling between the posterior hippocampus and a selection of these regions. Differences in age-related hippocampal-cortical, but not within-hippocampus circuitry selectively predicted worse memory performance. Our findings comprehensively characterize hippocampal functional topography in relation to cognition in older age, suggesting that shifts in cortico-hippocampal connectivity may be sensitive markers of age-related episodic memory decline.

Regulatory mechanism of cold-inducible diapause in Caenorhabditis elegans.

Temperature is a critical environmental cue that controls the development and lifespan of many animal species; however, mechanisms underlying low-temperature adaptation are poorly understood. Here, we describe cold-inducible diapause (CID), another type of diapause induced by low temperatures in Caenorhabditis elegans. A premature stop codon in heat shock factor 1 (hsf-1) triggers entry into CID at 9 °C, whereas wild-type animals enter CID at 4 °C. Furthermore, both wild-type and hsf-1(sy441) mutant animals undergoing CID can survive for weeks, and resume growth at 20 °C. Using epistasis analysis, we demonstrate that neural signalling pathways, namely tyraminergic and neuromedin U signalling, regulate entry into CID of the hsf-1 mutant. Overexpression of anti-ageing genes, such as hsf-1, XBP1/xbp-1, FOXO/daf-16, Nrf2/skn-1, and TFEB/hlh-30, also inhibits CID entry of the hsf-1 mutant. Based on these findings, we hypothesise that regulators of the hsf-1 mutant CID may impact longevity, and successfully isolate 16 long-lived mutants among 49 non-CID mutants via genetic screening. Furthermore, we demonstrate that the nonsense mutation of MED23/sur-2 prevents CID entry of the hsf-1(sy441) mutant and extends lifespan. Thus, CID is a powerful model to investigate neural networks involving cold acclimation and to explore new ageing mechanisms.

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.

Investigating grey matter volumetric trajectories through the lifespan at the individual level.

Adolescents exhibit remarkable heterogeneity in the structural architecture of brain development. However, due to limited large-scale longitudinal neuroimaging studies, existing research has largely focused on population averages, and the neurobiological basis underlying individual heterogeneity remains poorly understood. Here we identify, using the IMAGEN adolescent cohort followed up over 9 years (14-23 y), three groups of adolescents characterized by distinct developmental patterns of whole-brain gray matter volume (GMV). Group 1 show continuously decreasing GMV associated with higher neurocognitive performances than the other two groups during adolescence. Group 2 exhibit a slower rate of GMV decrease and lower neurocognitive performances compared with Group 1, which was associated with epigenetic differences and greater environmental burden. Group 3 show increasing GMV and lower baseline neurocognitive performances due to a genetic variation. Using the UK Biobank, we show these differences may be attenuated in mid-to-late adulthood. Our study reveals clusters of adolescent neurodevelopment based on GMV and the potential long-term impact.