Longevity Advantage Research Articles

Epigenetic predictors of species maximum life span and other life-history traits in mammals.

By analyzing 15,000 samples from 348 mammalian species, we derive DNA methylation (DNAm) predictors of maximum life span (R = 0.89), gestation time (R = 0.96), and age at sexual maturity (R = 0.85). Our maximum life-span predictor indicates a potential innate longevity advantage for females over males in 17 mammalian species including humans. The DNAm maximum life-span predictions are not affected by caloric restriction or partial reprogramming. Genetic disruptions in the somatotropic axis such as growth hormone receptors have an impact on DNAm maximum life span only in select tissues. Cancer mortality rates show no correlation with our epigenetic estimates of life-history traits. The DNAm maximum life-span predictor does not detect variation in life span between individuals of the same species, such as between the breeds of dogs. Maximum life span is determined in part by an epigenetic signature that is an intrinsic species property and is distinct from the signatures that relate to individual mortality risk.

The association between body height and longevity: evidence from a national population sample.

A wealth of research suggests that taller individuals are healthier and live longer than their shorter counterparts, although conflicting results have been reported. This study aims to investigate whether taller individuals in Poland exhibit greater longevity compared to their shorter counterparts. Data on declared height were collected from 848,860 adults who died in the years 2004-2008 in Poland. To eliminate the cohort effects, Z-values were computed. Pearson's correlation coefficients were calculated independently for males and females. Subsequently, one way ANOVA was performed. The correlation between adult height and longevity was negative and statistically significant in both men and women. After eliminating the effects of secular trends in height, the correlation was very weak (r = -0.0044 in men and r = -0.0038 in women) but significant (p = 0.023 and p = 0.022, respectively). Despite the significant correlation observed between the two variables, it should be noted that the relationship between height and longevity is very weak and tenuous. Overall, these results do not support the hypothesis that taller individuals have a longevity advantage. Further research is warranted to identify the underlying biological mechanisms driving this phenomenon as well as to explore additional variables affecting human longevity.

The vanishing advantage of longevity in Nicoya, Costa Rica: A cohort shift

The vanishing advantage of longevity in Nicoya, Costa Rica: A cohort shift

The determinants of longevity: The perspectives from East Asian economies.

The determinants of longevity: The perspectives from East Asian economies.

COVID-19 mortality among Jews in 2020: a global overview and lessons taught about the Jewish longevity advantage.

An extensive body of demographic literature has described Jews as 'long-lifers'. From the mid-nineteenth century onwards, this pattern affected all age groups and was particularly well expressed among Jewish males but was also present among Jewish females. It held good independently of the Jews' socio-economic position. This became known as 'Jewish pattern of mortality'. This paper has two aims. The first aim is to show the impact of COVID-19 on Jewish mortality. This is a study of a global pandemic in the Jewish population which is, to the best of our knowledge, unique in its scope and quality. The second aim is to settle the finding of relatively high mortality from COVID-19 in certain Jewish communities ('Jewish penalty' in relation to COVID-19) with the notion of 'Jewish pattern of mortality'. The author proceeds to show that the status of Jews as a low mortality group under a Western epidemiological regime, when mortality and morbidity are dominated by non-communicable diseases, does not stand in contradiction to a higher vulnerability among Jews to coronavirus. Thus, the paper further develops understanding of mortality of Jews and serves as a contribution to ethnic and religious demography and epidemiology.

Do the short die young? Evidence from a large sample of deceased Polish adults

Body height is associated with various socioeconomic and health-related outcomes. Despite numerous studies, the relationship between stature and longevity remains uncertain. This study explores the association between self-reported height and lifespan. Data from 848,860 adults who died between 2004 and 2008 in Poland were collected. After excluding a small proportion of records due to missing data or errors, we examined records for 848,387 individuals (483,281 men, age range: 20–110 years; 365,106 women, age range: 20–112 years). Height was expressed as standardized residual variance derived from linear regression in order to eliminate the variance of year of birth on height. After the elimination of the cohort effect, five height classes were designated using centiles: very short, short, medium, tall and very tall. The differences between sexes and among classes were evaluated with two-way ANOVA and post hoc Tukey’s test. The effect size was assessed using partial eta squared (η2). Pearson’s r coefficients of correlation were calculated. The effect of sex on lifespan was nearly 17 times stronger than the effect of height. No correlation between height and lifespan was found. In conclusion, these findings do not support the hypothesis that taller people have a longevity advantage. We offer tentative explanations for the obtained results.

Trends in the Female Longevity Advantage of 19th-Century Birth Cohorts: Exploring the Role of Place and Fertility

Trends in the Female Longevity Advantage of 19th-Century Birth Cohorts: Exploring the Role of Place and Fertility

CELLULAR RESPIRATION AND RESILIENCE AS A POTENTIAL BIOLOGICAL MECHANISM DRIVING SEX DIFFERENCES IN AGING

Abstract There are substantial differences in the progression of aging between males and females including in progression and prevalence of disease and longevity. Not all can be explained solely by sex-specific endocrine regulation and growing evidence suggests there are basic biological and genetic differences in sex that drive disparity in physiological function. In this study, we describe metabolic differences at the cellular level that both define some of these biological differences as well as provide a potential mechanism for delineating relevant molecular mechanisms of aging. Using HET3 mice, a genetically heterogeneous model with a consistent female advantage in longevity, we show that primary fibroblast lines retain functional metabolic characteristics, including mitochondrial response and stress resilience, which are representative of the sex of the donor animal. These differences persist even after several rounds of passage using standard culturing techniques suggesting these differences are not driven by direct impact of circulating sex hormones. Moreover, we find that differences in these cellular responses have some predictive power to determine both sex- and individual-specific responses to physiological challenge including obesity and longevity. In addition, we are able to use this model to delineate how donor sex affects cellular responses within defined pillars of aging including proteostasis, metabolic function, and adaption to stress. Overall, our model then provides valuable in defining the cellular responses that contribute to the mammalian aging process.

Low-Dose Enzalutamide in Metastatic Prostate Cancer-Longevity Over Conventional Survival Analysis.

Enzalutamide is an important drug in the treatment of prostate cancer. Standard dosing often requires dose reduction because of side effects. There is no information on survival outcomes with lower doses. We investigated the impact of starting enzalutamide at ≤ 50% dose on metastatic prostate cancer outcomes including patients' longevity. Records of metastatic prostate cancer patients treated with enzalutamide at one center were retrospectively reviewed. Low-dose enzalutamide (≤80 mg/day) was compared with standard-dose (160 mg/day). The primary objective was to compute the restricted mean survival time (RMST - time scale) and restricted mean attained age (RMAA - age scale) using the Irwin method. Secondary objectives included overall survival (OS), progression-free survival (PFS), and PSA progression per PCWG3 criteria (PSA PFS). We used the logrank test and the ∆ difference between RMSTs for comparison. Of 111 patients treated, 32 received a low-dose and 79 the standard-dose. Low-dose patients had less prior abiraterone or chemotherapy (28.1% vs. 65.8%, P < .001); more testosterone assessment (65.6% vs. 40.5%, P=.016); poorer ECOG performance status (48.3% score ≥2 vs. 26.6%; P=.040), more comorbidities (75.9% vs. 46.3%; P=.010)) including increased cardiovascular disease (51.7% vs. 21.4%, P=.004). Baseline PSA value and doubling time at start of enzalutamide and distribution of metastases were similar between the groups. OS and PFS did not differ between low-dose and standard-dose. Patients on low-dose had a better longevity with significantly longer RMAA, 89.1 years, versus standard-dose RMAA of 83.8 years (∆=5.3 years, P=.003, logrank P=.025). In a subgroup analysis by age at start of enzalutamide, <75 versus ≥75 years old, longevity was also better with low-dose in younger patients (∆=2.9 years, P=.034, and older, ∆=3.3 years, P=.011). The longevity advantage and reduced adverse events seen in patients with prostate cancer treated with low-dose enzalutamide warrants further investigation.

In the Mind of the US Olympic Athletes; Longevity Advantage and Its Relation to Nervous System Disorders and Mental Illness

In a recent study of 8124 US Olympic athletes, Antero et al. [1] found that the US Olympic athletes live 5 years longer than their general counterparts.This longevity advantage was mainly driven by the lower risk of the major two causes of death, i.e. cardiovascular diseases and cancer.

High hopes: lower risk of death due to mental disorders and self-harm in a century-long US Olympian cohort compared with the general population

ObjectiveTo determine the risk of death due to prominent mental disorders, substance abuse, and self-harm among US Olympians compared with the general population.MethodsAll female (n=2301) and male (n=5823) US Olympians...

Exploring the longevity advantage of doctorates in Finland and Sweden: The role of smoking- and alcohol-related causes of death.

Aims: Tobacco smoking and alcohol use contribute to differences in life expectancy between individuals with primary, secondary and tertiary education. Less is known about the contribution of these risk factors to differences at higher levels of education. We estimate the contribution of smoking and alcohol use to the life-expectancy differences between the doctorates and the other tertiary-educated groups in Finland and in Sweden. Methods: We used total population data from Finland and Sweden from 2011 to 2015 to calculate period life expectancies at 40 years of age. We present the results by sex and educational attainment, the latter categorised as doctorate or licentiate degrees, or other tertiary. We also present an age and cause of death decomposition to assess the contribution of deaths related to smoking and alcohol. Results: In Finland, deaths related to smoking and alcohol constituted 48.6% of the 2.1-year difference in life expectancy between men with doctorate degrees and the other tertiary-educated men, and 22.9% of the 2.1-year difference between women, respectively. In Sweden, these causes account for 22.2% of the 1.9-year difference among men, and 55.7% of the 1.6-year difference among women, which in the latter case is mainly due to smoking. Conclusions: Individuals with doctorates tend to live longer than other tertiary-educated individuals. This difference can be partly attributed to alcohol consumption and smoking.

Lifespan of long-lived growth hormone receptor knockout mice was not normalized by housing at 30°C since weaning.

Growth hormone receptor knockout (GHRKO) mice are remarkably long‐lived and have improved glucose homeostasis along with altered energy metabolism which manifests through decreased respiratory quotient (RQ) and increased oxygen consumption (VO2). Short‐term exposure of these animals to increased environmental temperature (eT) at 30°C can normalize their VO2 and RQ. We hypothesized that increased heat loss in the diminutive GHRKO mice housed at 23°C and the consequent metabolic adjustments to meet the increased energy demand for thermogenesis may promote extension of longevity, and preventing these adjustments by chronic exposure to increased eT will reduce or eliminate their longevity advantage. To test these hypotheses, GHRKO mice were housed at increased eT (30°C) since weaning. Here, we report that contrasting with the effects of short‐term exposure of adult GHRKO mice to 30°C, transferring juvenile GHRKO mice to chronic housing at 30°C did not normalize the examined parameters of energy metabolism and glucose homeostasis. Moreover, despite decreased expression levels of thermogenic genes in brown adipose tissue (BAT) and elevated core body temperature, the lifespan of male GHRKO mice was not reduced, while the lifespan of female GHRKO mice was increased, along with improved glucose homeostasis. The results indicate that GHRKO mice have intrinsic features that help maintain their delayed, healthy aging, and extended longevity at both 23°C and 30°C.

EFFECT OF SOLVENTS IN CHROMATOGRAPHIC DETERMINATION OF SILDENAFIL CITRATE IN MARKETED FORMULATION

Chromatography is the procedure for analysing a multicomponent mixture of trace, minor or major constituent by separaationinto its individual fractions.For the analytical determination of sildenafil in pharmaceutical dosages forms an expeditious &amp; sensitive RP-HPLC method is described.The mobile phase composition for chromatographing sildenafil was acetonitrile: methanol: water(60:25:15, V/V/V) with a flow rate of 1mL/min using C18 column. The internal standard selected was racecadotril and its eluents were observed at 217nm. The retention time was 4.919 min for the drug. Between 5-200μg/mL the linearity of this method was observed. For analysis of drug in tablets, the depicted method was found to be appropriate. The results of the analysis was evaluated statistically. The method were found to be robust, accurate and economic with a major advantage of column longevity, as buffer was not used throughout the method. Hence the proposed method can be extended for routine analysis.

Multidimensional informatic deconvolution defines gender-specific roles of hypothalamic GIT2 in aging trajectories

In most species, females live longer than males. An understanding of this female longevity advantage will likely uncover novel anti-aging therapeutic targets. Here we investigated the transcriptomic responses in the hypothalamus – a key organ for somatic aging control – to the introduction of a simple aging-related molecular perturbation, i.e. GIT2 heterozygosity. Our previous work has demonstrated that GIT2 acts as a network controller of aging. A similar number of both total (1079-female, 1006-male) and gender-unique (577-female, 527-male) transcripts were significantly altered in response to GIT2 heterozygosity in early life-stage (2 month-old) mice. Despite a similar volume of transcriptomic disruption in females and males, a considerably stronger dataset coherency and functional annotation representation was observed for females. It was also evident that female mice possessed a greater resilience to pro-aging signaling pathways compared to males. Using a highly data-dependent natural language processing informatics pipeline, we identified novel functional data clusters that were connected by a coherent group of multifunctional transcripts. From these it was clear that females prioritized metabolic activity preservation compared to males to mitigate this pro-aging perturbation. These findings were corroborated by somatic metabolism analyses of living animals, demonstrating the efficacy of our new informatics pipeline.

Long-distance pollen dispersal during recent colonization favors a rapid but partial recovery of genetic diversity in Picea sitchensis.

Tree species in the northern hemisphere are currently subject to rapid anthropogenic climate change and are shifting their ranges in response. This prompts questions about the mechanisms allowing tree populations to respond quickly to selection pressures when establishing into new areas. Focusing on the northern expanding range edge of Picea sitchensis, a widespread conifer of western North America, we ask how genetic structure and diversity develop during colonization, and assess the role of demographic history in shaping the evolutionary trajectory of an establishing population. We combined 500yr of tree-ring and genotyping-by-sequencing data in 639 trees at the expansion front on the Kodiak Archipelago. We show that alleles accumulated rapidly during an increase in recruitment rate in the early 1700s. A shift from foreign to local pollen flow subsequently homogenized genetic structure at the expansion front. Taking advantage of the exceptional longevity of conifers, we highlight the major role of long-distance pollen dispersal in the rapid but incomplete recovery of genetic diversity during the initial stages of colonization. We also warn that slow initial population growth as well as long-lasting dominance of local gene flow by early founders could increase evolutionary load under a rapidly changing climate.

The heart of the matter: years-saved from cardiovascular and cancer deaths in an elite athlete cohort with over a century of follow-up.

To quantify the years of life saved from cardiovascular (CVD), cancer and overall deaths among elite athletes according to their main type of physiological effort performed in the Olympic Games. All French athletes participating in the Games from 1912 to 2012, with vital status validated and cause of death (if concerned) identified by the national registries were included (n = 2814, 455 died) and classified according to 6 groups of effort: POWER (continuous effort < 45s); INTERMEDIATE (45s ≤ continuous effort < 600s); ENDURANCE (continuous effort ≥ 600s); POLYVALENT (participating in different events entering different classifications), INTERMITTENT (intermittent effort, i.e. team sports); PRECISION (targeting events). The theoretical years-lost method was adapted to calculate gains in longevity (years-saved) according to specific-risks under the competing risks model and was implemented in R software. Considering overall-deaths, all groups significantly saved, on average, 6.5years of life (95% CI 5.8-7.2) compared to the general population. This longevity advantage is mainly driven by a lower risk of cancer which, isolated, contributed to significantly save 2.3years of life (95% CI 1.2-1.9) on average in each group. The risk of CVD-related mortality in the ENDURANCE and PRECISION groups is not significantly different from the general population. The other groups significantly saved, on average, 1.6years of life (95% CI 1.2-1.9) from CVD death. The longevity benefits in elite athletes are associated with the type of effort performed during their career, mainly due to differences on the CVD-risk of death.

Génioplasties d’augmentation prothétiques et osseuses, à visée esthétique : revue de littérature et actualisation des connaissances

Chin augmentation is commonly practiced, whether in microgenia treatment, in cases of orthognathic or cosmetic surgery. Located at the crossroads of many specialties, the technique choice still differs according to the surgeon specialiy. A large number of publications on the subject are available. A comparaison between different surgical methods is therefore possible concerning their indications and their complication. The purpose of this study was to carry out a literature review, with updating knowledge, as well as a synthesis indication regarding aesthetic osseous and alloplastic genioplasty. Despite the generalization of "modern" implants in France, prosthetic genioplasty remains more frequently the source of serious complications (infections, extrusions, bone erosions). Similarly, this technique has much more limited indications than osseous genioplasty, which has the advantage of a better longevity. In order to increase the aesthetic appearance of the chin, osseous genioplasty should be performed more easily and more frequently by surgeons on all sides.

Highly variable lifespan in an annual reptile, Labord\u2019s chameleon (Furcifer labordi)

Among tetrapods, the current record holder for shortest lifespan is Labord’s chameleon, Furcifer labordi. These reptiles from the arid southwest of Madagascar have a reported lifespan of 4–5 months during the annual rainy season and spend the majority of their life (8–9 months) as a developing embryo. This semelparous, annual life history is unique among tetrapods, but only one population (Ranobe) in the southernmost distribution range has been studied. We therefore investigated the potential for environmentally-dependent variability in lifespan in a population in Kirindy Forest, which has a much longer warm rainy season. While no adults were found after March in Ranobe, the disappearance of adults was delayed by several months in Kirindy. Our data also revealed sex-biased mortality, suggesting that females have a longevity advantage. Furthermore, we found that, after an unusually long previous rainy season, one female was capable of surviving until a second breeding season. Keeping F. labordi in cages under ambient conditions demonstrated that also males can also survive until the next season of activity under these conditions. Our study therefore revealed considerable variability in the extreme life history of this tetrapod that is linked to variation in ecological factors.

Inducible knockdown of pregnancy-associated plasma protein-A gene expression in adult female mice extends life span.

SummaryPregnancy‐associated plasma protein‐A (PAPP‐A) knockout (KO) mice, generated through homologous recombination in embryonic stem cells, have a significantly increased lifespan compared to wild‐type littermates. However, it is unknown whether this longevity advantage would pertain to PAPP‐A gene deletion in adult animals. In the present study, we used tamoxifen (Tam)‐inducible Cre recombinase‐mediated excision of the floxed PAPP‐A (fPAPP‐A) gene in mice at 5 months of age. fPAPP‐A mice, which were either positive (pos) or negative (neg) for Tam‐Cre, received Tam treatment with quarterly boosters. Only female mice could be used with this experimental design. fPAPP‐A/neg and fPAPP‐A/pos mice had similar weights at the start of the experiment and showed equivalent weight gain. We found that fPAPP‐A/pos mice had a significant extension of life span (P = 0.005). The median life span was increased by 21% for fPAPP‐A/pos compared to fPAPP‐A/neg mice. Analysis of mortality in life span quartiles indicated that the proportion of deaths of fPAPP‐A/pos mice were lower than fPAPP‐A/neg mice at young adult ages (P = 0.002 for 601–800 days) and higher than fPAPP‐A/neg mice at older ages (P = 0.004 for >1000 days). Thus, survival curves and age‐specific mortality indicate that female mice with knockdown of PAPP‐A gene expression as adults have an extended healthy life span.