Longevity Study Research Articles

Bone Markers Are Diminished in Offspring of Long-Lived Families Compared With Matched Controls, but Respond Equally to T3 and rhTSH

Objective: We explored the effects of T3 and rhTSH administration on bone turnover in subjects of the Leiden Longevity Study. Design: Twenty-six subjects (13 offspring and 13 matched controls), mean age 68 y, underwent a rhTSH (0.1 mg i.m) and a T3 challenge (100 µg orally) with an interval of at least 3 m. Bone markers were measured at baseline and hereafter once daily for 3–4 days. Outcome Measures: Bone markers and changes after T3 and rhTSH. The influence of sex, group and time, and relations with incremental changes in TSH, fT4 and T3. Results: CTX (bone resorption) was lower in offspring than controls (mean ± SEM), 0.324±0.026 vs 0.443±0.036 ng/mL, P= 0.02. P1NP (bone formation) was also lower in offspring than in controls (40.3±2.2 vs 59.0± 4.7 ng/mL, P=0.004). No sex differences were found. In offspring, CTX but not P1NP was positively related to TSH and fT4 (R=0.48, P=0.001 and R=0.55, P=0.005). In controls, CTX was negatively related to TSH (R=-0.50, P=0.009), while P1NP was positively related with fT4 (R=0.52, P=0.006). TSH administration increased bone resorption and formation (P<0.0001 and 0.005, respectively). CTX was maximal at 48 h, increasing from 0.415±0.032 to 0.470 ±0.037 ng/mL, P=0.001. P1NP increased from 51.1±4.09 to a maximum of 56.2±3.9 ng/mL at 24 h (P=0.005). T3 also increased bone resorption (P=0.049) and formation (P=0.001). CTX increased from 0.386±0.034 to 0.410± 0.041 ng/mL, P=0.05, and P1NP from 48.9± 4.3 to 55.5±4.2 ng/mL, P=0.007), with maximal values at 48 h. Offspring and controls had similar responses and sex had generally no statistical impact. Significant linear regressions were found between the incremental changes of CTX and TSH at 24 h (R=0.44, P=0.003), but not later. Here, significant linear relation were found for the incremental fT4 and CTX (R=0.60, P=0.001 at 48 h, and R=0.49, P=0.013 at 72 h). For P1NP such relations were not present (R values between from 0.002 to 0.14). T3 changes did not correlate with bone markers at any time point. Conclusion: This study demonstrates that bone turnover is diminished in members of long-lived families where bone resorption was positively related to serum TSH and fT4. Nevertheless, the responses to TSH (and fT4) and T3 were similar in offspring and controls. Interestingly, the maximal effect of TSH increment on bone resorption preceded that of fT4, suggesting that TSH may have an independent stimulatory effect on bone resorption. At physiological TSH concentrations such stimulatory effect on bone resorption may be postulated in offspring, along with many other factors, e.g PTH, vitamin D, GH, sex hormones and cytokines.

Prevalence, Causes, and Factors Associated with Visual Impairment in a Chinese Elderly Population: The Rugao Longevity and Aging Study.

PurposeThis study aimed to explore the current prevalence, causes, and factors associated with visual impairment in a Chinese elderly population.MethodsA random sample of 2164 candidates aged ≥70 years was selected. Among them, 1914 participants (response rate: 88.4%) underwent comprehensive eye examinations. The prevalence and causes of visual impairment were estimated, and the associated factors were identified.ResultsThe standardized prevalence of mild visual impairment (<6/12 to ≥6/18), moderate to severe visual impairment (MSVI) (<6/18 to ≥3/60), and blindness (<3/60) in the better eye were 20.5%, 25.8%, and 3.4%, respectively. The leading cause of visual impairment was cataract (49.7%), followed by uncorrected refractive error (26.5%), myopic maculopathy (5.8%), and posterior capsular opacification (5.5%). Optical coherence tomography revealed that vitreoretinal interface abnormalities were the third most common cause of monocular mild visual impairment (2.2%) and MSVI (4.4%) in the elderly population. A large number of patients with visual impairment (81.7%) were amenable to undergo the interventions. Visual impairment was associated with advanced age (odds ratio [OR], 1.09 per year; p<0.001), female sex (OR, 1.59; p=0.003), self-reported visual impairment (OR, 1.91; p<0.001), cognitive impairment (OR, 1.40, p=0.005), and high educational level (OR, 0.75; primary, p=0.045; and OR, 0.53, secondary or higher; p<0.001).ConclusionVisual impairment was common in the Chinese elderly population and a severe health and social problem. Practicable policies are urgently needed to popularize eye health knowledge and promote treatments for visual impairment in elderly people in rural China.

Health and longevity studies in C. elegans: the \u201chealthy worm database\u201d reveals strengths, weaknesses and gaps of test compound-based studies

Several biogerontology databases exist that focus on genetic or gene expression data linked to health as well as survival, subsequent to compound treatments or genetic manipulations in animal models. However, none of these has yet collected experimental results of compound-related health changes. Since quality of life is often regarded as more valuable than length of life, we aim to fill this gap with the “Healthy Worm Database” (http://healthy-worm-database.eu). Literature describing health-related compound studies in the aging model Caenorhabditis elegans was screened, and data for 440 compounds collected. The database considers 189 publications describing 89 different phenotypes measured in 2995 different conditions. Besides enabling a targeted search for promising compounds for further investigations, this database also offers insights into the research field of studies on healthy aging based on a frequently used model organism. Some weaknesses of C. elegans-based aging studies, like underrepresented phenotypes, especially concerning cognitive functions, as well as the convenience-based use of young worms as the starting point for compound treatment or phenotype measurement are discussed. In conclusion, the database provides an anchor for the search for compounds affecting health, with a link to public databases, and it further highlights some potential shortcomings in current aging research.

Integrated genetic analyses revealed novel human longevity loci and reduced risks of multiple diseases in a cohort study of 15,651 Chinese individuals.

There is growing interest in studying the genetic contributions to longevity, but limited relevant genes have been identified. In this study, we performed a genetic association study of longevity in a total of 15,651 Chinese individuals. Novel longevity loci, BMPER (rs17169634; p = 7.91 × 10−15) and TMEM43/XPC (rs1043943; p = 3.59 × 10−8), were identified in a case–control analysis of 11,045 individuals. BRAF (rs1267601; p = 8.33 × 10−15) and BMPER (rs17169634; p = 1.45 × 10−10) were significantly associated with life expectancy in 12,664 individuals who had survival status records. Additional sex‐stratified analyses identified sex‐specific longevity genes. Notably, sex‐differential associations were identified in two linkage disequilibrium blocks in the TOMM40/APOE region, indicating potential differences during meiosis between males and females. Moreover, polygenic risk scores and Mendelian randomization analyses revealed that longevity was genetically causally correlated with reduced risks of multiple diseases, such as type 2 diabetes, cardiovascular diseases, and arthritis. Finally, we incorporated genetic markers, disease status, and lifestyles to classify longevity or not‐longevity groups and predict life span. Our predictive models showed good performance (AUC = 0.86 for longevity classification and explained 19.8% variance of life span) and presented a greater predictive efficiency in females than in males. Taken together, our findings not only shed light on the genetic contributions to longevity but also elucidate correlations between diseases and longevity.

An alternative food source for metabolism and longevity studies in Caenorhabditis elegans

Caenorhabditis elegans is an instrumental research model used to advance our knowledge in areas including development, metabolism, and aging. However, research on metabolism and/or other measures of health/aging are confounded by the nematode’s food source in the lab, live E. coli bacteria. Commonly used treatments, including ultraviolet irradiation and antibiotics, are successful in preventing bacterial replication, but the bacteria can remain metabolically active. The purpose of this study is to develop a metabolically inactive food source for the worms that will allow us to minimize the confounding effects of bacterial metabolism on worm metabolism and aging. Our strategy is to use a paraformaldehyde (PFA) treated E. coli food source and to determine its effects on worm health, metabolism and longevity. We initially determine the lowest possible concentrations of PFA necessary to rapidly and reproducibly kill bacteria. We then measure various aspects of worm behavior, healthspan and longevity, including growth rate, food attraction, brood size, lifespan and metabolic assessments, such as oxygen consumption and metabolomics. Our resulting data show that worms eat and grow well on these bacteria and support the use of 0.5% PFA-killed bacteria as a nematode food source for metabolic, drug, and longevity experiments.

Seed longevity of maize conserved under germplasm bank conditions for up to 60 years.

The long-term conservation of seeds of plant genetic resources is of key importance for food security and preservation of agrobiodiversity. Nevertheless, there is scarce information available about seed longevity of many crops under germplasm bank conditions. Through germination experiments as well as the analysis of historical monitoring data, we studied the decline in viability manifested by 1000 maize (Zea mays subsp. mays) seed accessions conserved for an average of 48 years at the CIMMYT germplasm bank, the largest maize seedbank in the world, under two cold storage conditions: an active (-3 °C; intended for seed distribution) and a base conservation chamber (-15 °C; for long-term conservation). Seed lots stored in the active chamber had a significantly lower and more variable seed germination, averaging 81.4 %, as compared with the seed lots conserved in the base chamber, averaging 92.1 %. The average seed viability detected in this study was higher in comparison with that found in other seed longevity studies on maize conserved under similar conditions. A significant difference was detected in seed germination and longevity estimates (e.g. p85 and p50) among accessions. Correlating seed longevity with seed traits and passport data, grain type showed the strongest correlation, with flint varieties being longer lived than floury and dent types. The more rapid loss of seed viability detected in the active chamber suggests that the seed conservation approach, based on the storage of the same seed accessions in two chambers with different temperatures, might be counterproductive for overall long-term conservation and that base conditions should be applied in both. The significant differences detected in seed longevity among accessions underscores that different viability monitoring and regeneration intervals should be applied to groups of accessions showing different longevity profiles.

Design and implementation framework of social assistive robotics for people with dementia - a scoping review

Nowadays, longevity studies have become a distinguished multidisciplinary field merging with cutting-edge computer science technologies to outline innovative ideas to cater to the needs of seniors. Since the global geriatric population is anticipated to rise, the number of people seeking to obtain caregiving services and wishing to be more actively engaged in life will be more apparent. Therefore, seniors aspiring day-to-day special care in home settings, interested in improving their living standards can likewise benefit from an amiable companion. A comprehensive search strategy was developed and selected databases were looked through with relevant keywords. This scoping review qualitatively examines the literature on the use of companion robots, including both pet-like and humanoid robots, and Internet-of-Things (IoT) security, coupled with the new 5G technology for the home-based elder care. From 355 full-text articles that were found, 90 articles were selected to be investigated respectively. In order to ascertain their operation in the future, we discuss remaining challenges, unused opportunities, security risks and suggested remedies and suggest a dementia-centred concept and an implementation framework.

Lantana camara ethanolic leaves extracts exhibit anti-aging properties in Drosophila melanogaster: survival-rate and life span studies.

In this article, we aimed to investigate the anti-aging activity of Lantana camara ethanolic leaves-extract in Drosophila melanogaster: survival and longevity (life span). L. camara leaves were collected and washed thoroughly of sand particles, air-dried, ground, and extracted by the maceration method using ethanol as a solvent. Phytochemical screening was carried out. 168-hour LC50 was determined by exposing fruit flies to concentrations ranging from 5 to 5000mg/10g diet for 7-days. Twenty-eight-day survival and longevity studies were carried out by administering L. camara ethanolic leaves extract at 5, 10, and 20mg/10g diet to 1-3days old fruit flies. Each concentration was replicated four times with 50 fruit flies each. The emergence rate of young fruit flies from eggs laid by fruit flies administered L. camara leaves-extracts were also carried out. The total yield of the extraction was determined to be 18%. Phytochemical analysis revealed the presence of alkaloids, Flavonoids, Phenol, steroids, cardiac glycosides, and carbohydrates. 168-hour LC50 of L. camara was also determined to be 1135mg/10g diet. L. camara significantly prolonged (P<0.05) survival rate and extended (P<0.05) D. melanogaster life span compared with control. L. camara significantly increased (P<0.05) emergence rate of young fruit flies from eggs laid by fruit flies administered L. camara ethanolic leaves extracts. From the experimental results, it can be concluded that the ethanol extract of L. camara leaves extended the life span of D. melanogaster at these concentrations. Due to similarities of conserved genes between humans and fruit flies, the use of L. camara ethanolic leaves extract at these concentrations is safe and may be recommended as herbal medicine in humans.

Analysis of distribution characteristics and influencing factors of healthy and long-lived people in Shanglin area of Nanning, Guangxi Zhuang Autonomous Region

Objective: To explore the epidemiologic characteristics of long-lived population and influencing factors in Shanglin county of Guangxi and provide scientific basis for the study of health and longevity in Guangxi. Methods: We collected and analyzed the general demographic cross-sectional data of the long-lived individuals (≥90 years old) in 11 villages and towns by multi-source registration and face-to-face interview. The age group control design was adopted to conduct a comparison among the longevity group (90-100 years old), centenarian group (≥100 years old), the longevity plus centenarian group and control group (local population aged 40-85 years), and identify the factors related to longevity. Results: Among the 496 007 people registered in Shanglin, 1 533 were aged ≥90 years, including 1 453 in the longevity group, with an average age of (92.84±2.46) years, and 80 in the centenarian group, with an average age of (102.67±2.60) years. The spatial distribution of long-lived individuals and centenarians was mainly in the north and central areas, and sparse in southwest area. Analysis on factors related to health and longevity indicated that old people with Zhuang ethnic (OR=1.551,95%CI:1.308-1.838), married (OR=55.507,95%CI:36.087-85.377) and moderately high waist-to-hip ratio (OR=258.056,95%CI:27.775-2 397.569), and SBP (OR=1.019,95%CI:1.013-1.026) tended to live longer. Conclusions: We found that the rate of longevity in Shanglin was higher than the average level in Guangxi and China. Longevity in Shanglin country had unique spatial and population distribution characterics of female longevity more than male longevity, mainly Zhuang ethnic and so on. Being women, married, family history of longevity, appropriate high waist-to-hip ratio, SBP and blood sugar level might be positive factors for longevity in Shanglin, but the impacts of other factors on longevity need further study.

Improved selection of participants in genetic longevity studies: family scores revisited

BackgroundAlthough human longevity tends to cluster within families, genetic studies on longevity have had limited success in identifying longevity loci. One of the main causes of this limited success is the selection of participants. Studies generally include sporadically long-lived individuals, i.e. individuals with the longevity phenotype but without a genetic predisposition for longevity. The inclusion of these individuals causes phenotype heterogeneity which results in power reduction and bias. A way to avoid sporadically long-lived individuals and reduce sample heterogeneity is to include family history of longevity as selection criterion using a longevity family score. A main challenge when developing family scores are the large differences in family size, because of real differences in sibship sizes or because of missing data.MethodsWe discussed the statistical properties of two existing longevity family scores: the Family Longevity Selection Score (FLoSS) and the Longevity Relatives Count (LRC) score and we evaluated their performance dealing with differential family size. We proposed a new longevity family score, the mLRC score, an extension of the LRC based on random effects modeling, which is robust for family size and missing values. The performance of the new mLRC as selection tool was evaluated in an intensive simulation study and illustrated in a large real dataset, the Historical Sample of the Netherlands (HSN).ResultsEmpirical scores such as the FLOSS and LRC cannot properly deal with differential family size and missing data. Our simulation study showed that mLRC is not affected by family size and provides more accurate selections of long-lived families. The analysis of 1105 sibships of the Historical Sample of the Netherlands showed that the selection of long-lived individuals based on the mLRC score predicts excess survival in the validation set better than the selection based on the LRC score .ConclusionsModel-based score systems such as the mLRC score help to reduce heterogeneity in the selection of long-lived families. The power of future studies into the genetics of longevity can likely be improved and their bias reduced, by selecting long-lived cases using the mLRC.

Sex, diabetes status and cognition: findings from the study of longevity in diabetes

IntroductionWomen comprise two-thirds of people with dementia, making female sex a significant dementia risk factor. Both type 1 diabetes (T1D) and type 2 diabetes (T2D) are known dementia risk factors...

Column Study of Cd(Ii) Removal and Longevity by Nitrate-Mediated Zero-Valent Iron with Mixed Anaerobic Microorganisms

Column Study of Cd(Ii) Removal and Longevity by Nitrate-Mediated Zero-Valent Iron with Mixed Anaerobic Microorganisms

Prospects for the study of active longevity among researchers

Prospects for the study of active longevity among researchers

Variants of FOXO3 and RPA3 genes affecting IGF-1 levels alter the risk of development of primary osteoarthritis.

Pathologically high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels in patients with acromegaly are associated with arthropathy. Several studies highlight the potential role of the GH/IGF-1 axis in primary osteoarthritis (OA). We aimed to disentangle the role of IGF-1 levels in primary OA pathogenesis. Patients from the Genetics osteoARthritis and Progression (GARP) Study with familial, generalized, symptomatic OA (n = 337, mean age: 59.8 ± 7.4 years, 82% female) were compared to Leiden Longevity Study (LLS) controls (n = 456, mean age: 59.8 ± 6.8 years, 51% female). Subjects were clinically and radiographically assessed, serum IGF-1 levels were measured, and 10 quantitative trait loci (QTL) in the FOXO3, IGFBP3/TNS3, RPA3, SPOCK2 genes, previously related to serum IGF-1 levels, were genotyped. Linear or binary logistic generalized estimating equation models were performed. Serum IGF-1 levels were increased in OA patients, with male patients exhibiting the strongest effect (males OR = 1.10 (1.04-1.17), P=0.002 vs females OR = 1.04 (1.01-1.07), P = 0.02). Independent of the increased IGF-1 levels, male carriers of the minor allele of FOXO3 QTL rs4946936 had a lower risk to develop hip OA (OR = 0.41 (0.18-0.90), P = 0.026). Additionally, independent of IGF-1 levels, female carriers of the minor alleles of RPA3 QTL rs11769597 had a higher risk to develop knee OA (OR = 1.90 (1.20-2.99), P = 0.006). Patients with primary OA had significantly higher IGF-1 levels compared to controls. Moreover, SNPs in the FOXO3 and RPA3 genes were associated with an altered risk of OA. Therefore, altered IGF-1 levels affect the development of OA, and are potentially the result of the pathophysiological OA process.

Use of machine learning approach to predict depression in the elderly in China: A longitudinal study

BackgroundEarly detection of potential depression among elderly people is conducive for timely preventive intervention and clinical care to improve quality of life. Therefore, depression prediction considering sequential progression patterns in elderly needs to be further explored. MethodsWe selected 1,538 elderly people from Chinese Longitudinal Healthy Longevity Study (CLHLS) wave 3–7 survey. Long short-term memory (LSTM) and six machine learning (ML) models were used to predict different depression risk factors and the depression risks in the elderly population in the next two years. Receiver operating curve (ROC) and decision curve analysis (DCA) were used to evaluate the prediction accuracy of the reference model and ML models. ResultsThe area under the ROC curve (AUC) values of logistic regression with lasso regularisation (AUC=0.629, p-value=0.020) was the highest among ML models. DCA results showed that the net benefit of six ML models was similar (threshold: 0.00-0.10), the net benefit of lasso regression was the largest (threshold: 0.10-0.17 and 0.22-0.25), and the net benefit of DNN was the largest (threshold: 0.17–0.22 and 0.25–0.40). In two ML models, activities of daily living (ADL)/ instrumental ADL (IADL), self-rated health, marital status, arthritis, and number of cohabiting were the most important predictors for elderly with depression. LimitationsThe retrospective waves used in the LSTM model need to be further increased. ConclusionThe decision support system based on the proposed LSTM+ML model may be very valuable for doctors, nurses and community medical providers for early diagnosis and intervention.

Intrapopulation analysis of longitudinal lifespan in Caenorhabditis elegans identifies W09D10.4 as a novel AMPK-associated healthspan shortening factor

Caenorhabditis elegans is a model organism widely used for longevity studies. Current advances have been made in the methods that allow automated monitoring of C. elegans behavior. However, ordinary manual assays as well as automated methods have yet to achieve qualitative whole-life analysis of C. elegans longevity based on intrapopulation variation. Here, we utilized live-cell analysis system to determine the parameters of nematode lifespans. Image-based superposition method enabled to determine not only frailty in worms, but also to measure individual and longitudinal lifespan, healthspan, and frailspan. Notably, k–means clustering via principal component analysis revealed four clusters with distinct longevity patterns in wild-type C. elegans. Physiological relevance of clustering was confirmed by assays with pharmacological and/or genetic manipulation of AMP-activated protein kinase (AMPK), a crucial regulator of healthspan. Finally, we focused on W09D10.4 among the possible regulators extracted by integrative expression analysis with existing data sets. Importantly, W09D10.4 knockdown increased the high-healthspan populations only in the presence of AMPK, suggesting that W09D10.4 is a novel AMPK-associated healthspan shortening factor in C. elegans. Overall, the study establishes a novel platform of longitudinal lifespan in C. elegans, which is user-friendly, and may be a useful pharmacological tool to identify healthspan modulatory factors.

What Factors Influence the Perception of Longevity?

Previous research has highlighted the link between health-related factors and longevity. In particular, indices such as poor cardiovascular reactivity, high BMI, stress, and respiratory functioning have been shown to increase risk of mortality. However, little is known about identifying specific health and psychosocial behaviors that compromise the perception of longevity in African Americans. The Study of Longevity and Stress in African Americans (SOLSAA) was designed to examine psychosocial and health factors that are characteristic of survivorship in African Americans families. Data from 570 participants in the SOLSAA were used to examine the relationship between psychosocial and health-related factors among individuals aged 50 to 99 years (M = 67.6, SD = 11.5). Perception of longevity was positively correlated with sex, r = .058, education, r = .021, diastolic blood pressure r = .067, respiratory functioning, r = .150 and body mass index, r = .027, but negatively correlated with age, r = -.205, systolic blood pressure, r = -.050, and perceived stress, r = -.106. Regression analyses revealed, not surprisingly, that as participants aged, perception of longevity decreased. Furthermore, women’s perception of longevity was greater than that of men even after controlling for age. Given the longer life expectancy for women, this was also expected. Interestingly, high levels of perceived stress predicted reduced perception of longevity. These preliminary results suggest that the perception of stress is an important psychosocial factor for older African American’s self-forecasting of their chances for longevity beyond just simply age or physical health status.

Circulating Procollagen Type III N-Terminal Peptide and Physical Function in the Long Life Family Study

Circulating levels of procollagen type III N-terminal peptide (P3NP) may reflect increased fibrosis of skeletal muscle and other tissues with aging. In the current study, we tested if P3NP levels were associated with baseline and 7-year change in physical function among adults aged 39-104. Participants (n=400) were from the Long Life Family Study, a study of exceptional familial longevity. Plasma P3NP concentration was measured using a sandwich enzyme-linked immunosorbent assay (inter-assay CVs <3%). At baseline and 7-year follow-up visits, physical function was measured using the Short Physical Performance Battery (score 0-12), which consists of gait speed, balance, and chair-rise tests. Grip strength was measured using a handheld dynamometer. The association between log-transformed P3NP and physical function was examined using Generalized Estimating Equations adjusted for familial relatedness, age, sex, height, weight, lifestyle characteristics, chronic disease prevalence and inflammatory cytokines. Participants were aged 73.1 ± 15.2 years, 54% female, had a BMI of 26.6 ± 4.3 kg/m2, and a gait speed of 1.0 ± 0.3 m/s. One standard deviation higher P3NP concentration was related to worse baseline SPPB score (β=-0.9points), gait speed (β=-0.05m/s), chair-rise time (β=8.34seconds), and grip strength (β=-2.0kg; all p<0.001). Higher P3NP concentration was also associated with greater declines in gait speed (β=-1.41, p<.001) and chair-rise performance (β=0.41, p<.001). Plasma P3NP concentration may be a strong, novel biomarker of current and physical function changes with aging. Future research is needed to extend our findings to a larger population, and determine the mechanisms underlying these associations.

Neutrophil-Lymphocyte Ratio and Mortality in the Long Life Family Study

Neutrophil to Lymphocyte Ratio (NLR) reflects the balance between the innate (neutrophils) and adaptive (lymphocytes) immunity. Though NLR is a strong predictor of mortality in the general population, the distribution of NLR and its association with mortality has not been evaluated in families with exceptional longevity. Hence, we evaluated this question in the Long Life Family Study, a family based study of exceptional longevity. We used data from offspring of long lived (n=2065) family members and spousal controls (n=673). We used multivariate linear regression models adjusted for age, family relatedness, sex, field center, BMI and comorbidities (diabetes, CVD, cancer) to evaluate differences in NLR between long lived family members and spousal controls. Cox proportional hazard models were used to examine the association between NLR and mortality. 157 (7.6%) offspring in long lived families and 68 (10.1%) spousal controls were deceased during 12 years of follow up. NLR was similar among offspring in long lived families and spousal controls (1.96±1.06 vs.1.98±1.28; p=0.64). There was a significant positive association between NLR and overall mortality [HR: 1.3, 95% CI (1.01, 1.67)), p:0.04]. There was no statistically significant difference in this association among offspring in long lived families and spousal controls (p for interaction =0.16). The association between NLR and overall mortality was no longer significant [HR: 1.24; p:0.36] after adjustment for IL-6 and hsCRP. These results suggest that NLR may be a predictor of mortality in families with exceptional longevity though this association may not be independent of other inflammatory biomarkers.

Identifying Translational Longevity Targets With Genetically Mediated Transcriptome-Wide Association Studies

We hypothesized that trait associations with genetically mediated gene expression could be used to screen for genes that are good candidates for translational studies of longevity. We compiled a collection of genetically-mediated transcriptome-wide association studies using 33 traits and outcomes from large-scale, publicly-available GWAS meta-analysis results. The traits/outcomes were grouped within eight categories (aging, anthropometric, cardiovascular, inflammation, lung function, metabolic, musculoskeletal, and neurological). To test the utility of this approach, we examined trait associations with the drug target of statins, and we correctly identified known therapeutic effects and adverse events of statins. Specifically addressing the hypothesis, we examined a collection of candidate longevity-associated genes and identified one gene associated with lifespan that appears to also be associated with protection from atrial fibrillation and hearing impairment without being associated with adverse events. This screening approach can be used to prioritize gene targets for longevity translational efforts.