Variation In Lifespan Research Articles

Antioxidant supplementation slows telomere shortening in free-living white stork chicks.

Telomere length (TL) and shortening is increasingly shown to predict variation in survival and lifespan, raising the question of what causes variation in these traits. Oxidative stress is well known to accelerate telomere attrition in vitro, but its importance in vivo is largely hypothetical. We tested this hypothesis experimentally by supplementing white stork (Ciconia ciconia) chicks with antioxidants. Individuals received either a control treatment, or a supply of tocopherol (vitamin E) and selenium, which both have antioxidant properties. The antioxidant treatment increased the concentration of tocopherol for up to two weeks after treatment but did not affect growth. Using the telomere restriction fragment technique, we evaluated erythrocyte TL and its dynamics. Telomeres shortened significantly over the 21 days between the baseline and final sample, independent of sex, mass, size and hatching order. The antioxidant treatment significantly mitigated shortening rate of average TL (-31% in shorter telomeres; percentiles 10th, 20th and 30th). Thus, our results support the hypothesis that oxidative stress shortens telomeres in vivo.

Going beyond Lifespan in Comparative Biology of Aging

Over the last few decades, comparative biology of aging has aimed to identify factors responsible for the huge variability in lifespan observed across the animal kingdom. While these studies have undeniably improved our understanding of the complex processes that shape lifespan, we argue that time has now come to focus on specific aging metrics (e.g., age at the onset of aging, rate of aging) rather than on lifespan. Such a shift in research programs would help decipher the fine-scale mechanisms shaping age-specific mortality profiles across the tree of life.

Accounting for phylogenetic relatedness in cross-species analyses of telomere shortening rates

AbstractTelomeres are repeating DNA sequences found on the ends of chromosomes, which shorten with age and are implicated in senescence. Cross-species analyses of telomere shortening rates (TSR) and telomere lengths are important for understanding mechanisms underlying senescence, lifespan and life-history strategies of different species. Whittemore et al. (2019) generated a new dataset on variation in TSR, lifespan and body mass. In phylogenetically uncorrected analyses they found that TSR negatively correlates with lifespan. We re-ran analyses of their dataset using appropriate phylogenetic corrections. We found a strong phylogenetic signal in the association between TSR and body mass. We were able to corroborate Whittemore et al.’s major findings, including while correcting for body mass in a multivariate analysis. Since laboratory mice have different telomere lengths and potentially different telomere dynamics than wild mice, we removed mice from the analysis, which attenuates most associations.

Is austerity responsible for the recent change in mortality trends across high-income nations? A protocol for an observational study

IntroductionMortality rates in many high-income countries have changed from their long-term trends since around 2011. This paper sets out a protocol for testing the extent to which economic austerity can...

Prescription Drug Misuse: Taking a Lifespan Perspective.

Prescription drug misuse (PDM), or medication use without a prescription or in ways not intended by the prescriber, is a notable public health concern, especially in the United States. Accumulating research has characterized PDM prevalence and processes, but age-based or lifespan changes in PDM are understudied. Given age-based differences in the medical or developmental concerns that often underlie PDM, it is likely that PDM varies by age. This review summarizes the literature on PDM across the lifespan, examining lifespan changes in prevalence, sources, motives and correlates for opioid, stimulant, and tranquilizer/sedative (or benzodiazepine) PDM. In all, prevalence rates, sources and motives vary considerably by age group, with fewer age-based differences in correlates or risk factors. PDM prevalence rates tend to decline with aging, with greater use of physician sources and greater endorsement of self-treatment motives in older groups. Recreational motives (such as to get high) tend to peak in young adulthood, with greater use of peer sources or purchases to obtain medication for PDM in younger groups. PDM co-occurs with other substance use and psychopathology, including suicidality, across age groups. The evidence for lifespan variation in PDM is strongest for opioid PDM, with a need for more research on tranquilizer/sedative and stimulant PDM. The current literature is limited by the few studies of lifespan changes in PDM within a single sample, a lack of longitudinal research, little research addressing PDM in the context of polysubstance use, and little research on minority groups, such as sexual and gender minorities.

Age-related structural and functional variations in 5,967 individuals across the adult lifespan.

Exploring brain changes across the human lifespan is becoming an important topic in neuroscience. Though there are multiple studies which investigated the relationship between age and brain imaging, the results are heterogeneous due to small sample sizes and relatively narrow age ranges. Here, based on year‐wise estimation of 5,967 subjects from 13 to 72 years old, we aimed to provide a more precise description of adult lifespan variation trajectories of gray matter volume (GMV), structural network correlation (SNC), and functional network connectivity (FNC) using independent component analysis and multivariate linear regression model. Our results revealed the following relationships: (a) GMV linearly declined with age in most regions, while parahippocampus showed an inverted U‐shape quadratic relationship with age; SNC presented a U‐shape quadratic relationship with age within cerebellum, and inverted U‐shape relationship primarily in the default mode network (DMN) and frontoparietal (FP) related correlation. (b) FNC tended to linearly decrease within resting‐state networks (RSNs), especially in the visual network and DMN. Early increase was revealed between RSNs, primarily in FP and DMN, which experienced a decrease at older ages. U‐shape relationship was also revealed to compensate for the cognition deficit in attention and subcortical related connectivity at late years. (c) The link between middle occipital gyrus and insula, as well as precuneus and cerebellum, exhibited similar changing trends between SNC and FNC across the adult lifespan. Collectively, these results highlight the benefit of lifespan study and provide a precise description of age‐related regional variation and SNC/FNC changes based on a large dataset.

The association between stressors and telomeres in non-human vertebrates: a meta-analysis.

Animal response to stressors such as harsh environmental conditions and demanding biological processes requires energy generated through increased mitochondrial activity. This results in the production of reactive oxygen species (ROS). In vitro and some in vivo studies suggest that oxidative damage of DNA caused by ROS is responsible for telomere shortening. Since telomere length is correlated with survival in many vertebrates, telomere loss is hypothesised to trigger cellular ageing and/ or to reflect the harshness of the environment an individual has experienced. To improve our understanding of stress-induced telomere dynamics in non-human vertebrates, we analysed 109 relevant studies in a meta-analytical framework. Overall, the exposure to possible stressors was associated with shorter telomeres or higher telomere shortening rate (average effect size = -0.16±0.03). This relationship was consistent for all phylogenetic classes and for all a priori-selected stressor categories. It was stronger in the case of pathogen infection, competition, reproductive effort and high activity level, which emphasises their importance in explaining intraspecific telomere length variability and, potentially, lifespan variability. Interestingly, the association between stressor exposure and telomeres in one hand, and oxidative stress in the other hand, covaried, suggesting the implication of oxidative stress in telomere dynamics.

Research on Structural behavior of Composite Materials on different Cantilever Structures using FSI

The implementation of composite materials in industries like aerospace, automotive, civil, naval, etc., are emerging continuously because of its combined unique effects. The present article deals with a numerical simulation of the natural frequency effect on the different cantilever structure for various composite materials also estimates its structural response to aerodynamic forces using Fluid-Solid Interaction (FSI) in Ansys Workbench environment. This work is intended to analyze and learn the response of various real-time structural parameters like maximum deformation, maximum stress-induced location and modal parameters like modal frequency, mode shapes on different Cantilevered structures. Structures like wind turbines, airplane wings are critical in structural behavior, which are characteristically using the wind to produce power and lift respectively. The present article deals with an estimation of natural frequencies for the prediction of working lifespan and structural parameters variation throughout the cantilever structures to multi-purpose usage. The entire comparative part of this article is executed with an acceptable simulation of the displacement and principal stress for different composite materials such as Kevlar, Glass Fiber Reinforced Plastic (GFRP) and Carbon Fiber Reinforced Plastic (CFRP) by using FSI. Composites Beams are modeled in CATIA and discretized in the Ansys ACP 16.2 tool and Modal analysis of various cross-sectional beams are reported, compared and discussed.

Demographic plasticity facilitates ecological and economic resilience in a commercially important reef fish.

Variation in life-history characteristics is evident within and across animal populations. Such variation is mediated by environmental gradients and reflects metabolic constraints or trade-offs that enhance reproductive outputs. While generalizations of life-history relationships across species provide a framework for predicting vulnerability to overexploitation, deciphering patterns of intraspecific variation may also enable recognition of peculiar features of populations that facilitate ecological resilience. This study combines age-based biological data from geographically disparate populations of bluespine unicornfish (Naso unicornis)-the most commercially valuable reef-associated species in the insular Indo-Pacific-to explore the magnitude and drivers of variation in life span and examine the mechanisms enabling peculiar mortality schedules. Longevity and mortality schedules were investigated across eleven locations encompassing a range of latitudes and exploitation levels. The presence of different growth types was examined using back-calculated growth histories from otoliths. Growth-type-dependent mortality (mortality rates associated with particular growth trajectories) was corroborated using population models that incorporated size-dependent competition. We found a threefold geographic variation in life span that was strongly linked to temperature, but not to anthropogenic pressure or ocean productivity. All populations consistently displayed a two-phase mortality schedule, with higher than expected natural mortality rates in earlier stages of post-settlement life. Reconstructed growth histories and population models demonstrated that variable growth types within populations can yield this peculiar biphasic mortality schedule, where fast growers enjoy early reproductive outputs at the expense of greater mortality, and benefits for slow growers derive from extended reproductive outputs over a greater number of annual cycles. This promotes population resilience because individuals can take advantage of cycles of environmental change operating at both short- and long-term scales. Our results highlight a prevailing, fundamental misperception when comparing the life histories of long-lived tropical ectotherms: the seemingly incongruent combination of extended life spans with high mortality rates was enabled by coexistence of variable growth types in a population. Thus, a demographic profile incorporating contrasting growth and mortality strategies obscures the demographic effects of harvest across space or time in N. unicornis and possibly other ectotherms with the combination of longevity and asymptotic growth.

Twin consequences of rising U.S. death rates among young adults: Lower life expectancy and greater lifespan variability

The current study is an original investigation of the U.S. mortality pattern from 2000 to 2017. Previous research has shown that the unusual post-2014 decline in life expectancy is related to the increase in death rates for ages 25–44, mostly due to rising prevalence in drug poisoning and suicide deaths. Our investigation reveals that such increase in younger-age mortality has had an impact not only on life expectancy (or mean age at death), but also, and to a larger extent, on lifespan variability (the dispersion around the mean age at death). Even though lifespan variability is a key component of mortality change, as well as a measure of human well-being, with social, economic, and psychological implications, it has received much less attention than life expectancy has.

The threshold age of the lifetable entropy

Background: Indicators of relative variation of lifespans are markers of inequality at the population level and of uncertainty at the time of death at the individual level. In particular, the lifetable entropy H represents the elasticity of life expectancy to a change in mortality. However, it is unknown how this measure changes over time and whether a threshold age exists, as it does for other lifespan variation indicators. Results: The time derivative of H can be decomposed into changes in life disparity e† and life expectancy at birth eo. Likewise, changes over time in H are a weighted average of age-specific rates of mortality improvements. These weights reflect the sensitivity of H and show how mortality improvements can increase (or decrease) the relative inequality of lifespans. Further, we prove that in the assumption that mortality is reduced at all ages, H, as well as e†, has a threshold age below which saving lives reduces entropy, whereas improvements above that age increase entropy. Contribution: We give a formal expression for changes of H over time and provide a formal proof of the existence of a unique threshold age that separates reductions and increases in lifespan variation as a result age-specific mortality improvements.

Anti-aging interventions affect lifespan variability in sex, strain, diet and drug dependent fashion.

Decreased forkhead box O1 (FoxO1) activity induces hyperlipidemia and increased PPARγ, leading to hyperlipidemia in association with endoplasmic reticulum (ER) stress. In the liver, aging and comorbidities such as hyperlipidemia and diabetes significantly influence a wide variety of steatosis, but the underlying mechanisms are complex and remain elusive.To establish the modulatory role of FoxO1 and the functional consequences of its altered interaction with PPARγ in the present study, we utilized a cell culture system, aged rats and diabetic db/db mice.We found that, under ER stress, FoxO1 induces PPARγ-mediated lipid accumulation in aged rat livers. Our data showed that the FoxO1-induced hepatic lipid accumulation was negatively regulated by Akt signaling. PPARγ, a key lipogenesis transcription factor, was increased in aged liver, resulting in lipid accumulation via hepatic ER stress under hyperglycemic conditions. We further demonstrated that loss of FoxO1 causes a decline in PPARγ expression and reduces lipid accumulation. In addition, the interaction between FoxO1 and PPARγ was shown to induce hepatic steatosis in aging and db/db mice.We provide evidence that, in aged rats, FoxO1 interaction with PPARγ promotes hepatic steatosis, due to hyperglycemia-induced ER stress, which causes an impairment in Akt signaling, such in aging-related diabetes.

Latin American convergence and divergence towards the mortality profiles of developed countries

It is uncertain whether Latin America and Caribbean (LAC) countries are approaching a single mortality regime. Over the last three decades, LAC has experienced major public health interventions and the highest number of homicides in the world. However, these interventions and homicide rates are not evenly shared across countries. This study documents trends in life expectancy and lifespan variability for 20 LAC countries, 2000–14. By extending a previous method, we decompose differences in lifespan variability between LAC and a developed world benchmark into cause-specific effects. For both sexes, dispersion of amenable diseases through the age span makes the largest contribution to the gap between LAC and the benchmark. Additionally, for males, the concentration of homicides, accidents, and suicides in mid-life further impedes mortality convergence. Great disparity exists in the region: while some countries are rapidly approaching the developed regime, others remain far behind and suffer a clear disadvantage in population health.

Knockdown of the neuronal gene Lim3 at the early stages of development affects mitochondrial function and lifespan in Drosophila

Understanding the molecular mechanisms underlying variation in lifespan is central to ensure long life. Lim3 encoding a homolog of the vertebrate Lhx3/4 transcription factors plays a key role in Drosophila neuron development. Here, we demonstrated that Lim3 knockdown early in life decreased survival of adult flies. To study the mechanisms underlying this effect, we identified embryonic Lim3 targets using combined RNA-seq and RT-qPCR analyses complemented by in silico analysis of Lim3 binding sites. Though genes with neuronal functions were revealed as Lim3 targets, the characteristics of neurons were not affected by Lim3 depletion. Many of the direct and indirect Lim3 target genes were associated with mitochondrial function, ATP-related activity, redox processes and antioxidant defense. Consistent with the observed changes in the embryonic transcription of these genes, ROS levels were increased in embryos, which could cause changes in the transcription of indirect Lim3 targets known to affect lifespan. We hypothesize that altered mitochondrial activity is crucial for the decrease of adult lifespan caused by Lim3 knockdown early in life. In adults that encountered Lim3 depletion early in life, the transcription of several genes remained altered, and mitochondrial membrane potential, ATP level and locomotion were increased, confirming the existence of carry-over effects.

Leaf functional trait variation in a humid temperate forest, and relationships with juvenile tree light requirements.

The species-rich arborescent assemblages of humid tropical forests encompass much of the known range of the leaf economics spectrum, often including >20-fold variation in leaf lifespan. This suite of traits underpins a life-history continuum from fast-growing pioneers to slow-growing shade-tolerant species. Less is known about the range of leaf traits in humid temperate forests, and there are conflicting reports about relationships of these traits with the light requirements of temperate evergreen angiosperms. Here I quantify the range of leaf functional traits in a New Zealand temperate evergreen forest, and relationships of these traits with light requirements of juvenile trees and shrubs. Foliage turnover of saplings of 19 evergreen angiosperms growing beneath gaps (12–29% canopy openness) and in understories (1.2–2.9%) was measured over 12 months. Dry mass per area (LMA), dry matter content, thickness, density and nitrogen content (N) of leaves were also measured. Species minimum light requirements were indexed as the 10th percentile of the distribution of saplings in relation to canopy openness. Interspecific variation of leaf lifespan was ∼6-fold in gaps (0.6 to 3.8 yrs), and ∼11-fold in the understorey (0.7 to 7.7 yrs). Six small tree and shrub species are effectively leaf-exchangers, with leaf lifespans of c.1 year in gaps—albeit usually longer in the shade. Interspecific variation in other leaf traits was 2.5 to 4-fold. Lifespans and LMA of both sun and shade leaves were negatively correlated with species light requirements i.e., positively correlated with shade tolerance. However, light environment (gap vs shade) explained about the same amount of variation in LMA as species’ identity did. Species light requirements were not significantly correlated with leaf N, dry matter content, density or thickness—except for a marginally significant correlation with dry matter content of shade leaves. Species light requirements were thus less consistently related to leaf structural traits than appears to be the case in humid tropical forests. Whereas the wide interspecific variation in leaf economic traits of tropical rainforest species outweighs plastic response to light availability, temperate evergreen woody angiosperms appear to occupy a narrower range of the leaf economic spectrum. Standardization of the light environments in which LMA is measured is vital in comparative studies of humid temperate forest evergreens, because of countergradient responses of this trait to light, and because of the relative magnitudes of plastic and interspecific variation in LMA in these forests.

Global trends in lifespan inequality: 1950-2015.

Using data from the UN World Population Prospects, we document global trends in lifespan inequality from 1950 until 2015. Our findings indicate that (i) there has been a sustained decline in overall lifespan inequality, (ii) adult lifespan variability has also declined, but some plateaus and trend reversals have been identified, (iii) lifespan inequality among the elderly has increased virtually everywhere, and (iv) most of the world variability in age-at-death can be attributed to within-country variability. Such changes have occurred against a backdrop of generalized longevity increases. Our analyses suggest that the world is facing a new challenge: the emergence of diverging trends in longevity and age-at-death inequality among the elderly around the globe—particularly in high-income areas. As larger fractions of the world population survive to more advanced ages, it will be necessary for national and international health planners to recognize the growing heterogeneity that characterizes older populations.

The increasing lifespan variation gradient by area-level deprivation: A decomposition analysis of Scotland 1981–2011

Life expectancy inequalities are an established indicator of health inequalities. More recent attention has been given to lifespan variation, which measures the amount of heterogeneity in age at death across all individuals in a population. International studies have documented diverging socioeconomic trends in lifespan variation using individual level measures of income, education and occupation. Despite using different socioeconomic indicators and different indices of lifespan variation, studies reached the same conclusion: the most deprived experience the lowest life expectancy and highest lifespan variation, a double burden of mortality inequality. A finding of even greater concern is that relative differences in lifespan variation between socioeconomic group were growing at a faster rate than life expectancy differences. The magnitude of lifespan variation inequalities by area-level deprivation has received limited attention. Area-level measures of deprivation are actively used by governments for allocating resources to tackle health inequalities. Establishing if the same lifespan variation inequalities emerge for area-level deprivation will help to better inform governments about which dimension of mortality inequality should be targeted. We measure lifespan variation trends (1981–2011) stratified by an area-level measure of socioeconomic deprivation that is applicable to the entire population of Scotland, the country with the highest level of variation and one of the longest, sustained stagnating trends in Western Europe. We measure the gradient in variation using the slope and relative indices of inequality. The deprivation, age and cause specific components driving the increasing gradient are identified by decomposing the change in the slope index between 1981 and 2011. Our results support the finding that the most advantaged are dying within an ever narrower age range while the most deprived are facing greater and increasing uncertainty. The least deprived group show an increasing advantage, over the national average, in terms of deaths from circulatory disease and external causes.

Cellular energetics and mitochondrial uncoupling in canine aging.

The first domesticated companion animal, the dog, is currently represented by over 190 unique breeds. Across these numerous breeds, dogs have exceptional variation in lifespan (inversely correlated with body size), presenting an opportunity to discover longevity-determining traits. We performed a genome-wide association study on 4169 canines representing 110 breeds and identified novel candidate regulators of longevity. Interestingly, known functions within the identified genes included control of coat phenotypes such as hair length, as well as mitochondrial properties, suggesting that thermoregulation and mitochondrial bioenergetics play a role in lifespan variation. Using primary dermal fibroblasts, we investigated mitochondrial properties of short-lived (large) and long-lived (small) dog breeds. We found that cells from long-lived breeds have more uncoupled mitochondria, less electron escape, greater respiration, and capacity for respiration. Moreover, our data suggest that long-lived breeds have higher rates of catabolism and β-oxidation, likely to meet elevated respiration and electron demand of their uncoupled mitochondria. Conversely, cells of short-lived (large) breeds may accumulate amino acids and fatty acid derivatives, which are likely used for biosynthesis and growth. We hypothesize that the uncoupled metabolic profile of long-lived breeds likely stems from their smaller size, reduced volume-to-surface area ratio, and therefore a greater need for thermogenesis. The uncoupled energetics of long-lived breeds lowers reactive oxygen species levels, promotes cellular stress tolerance, and may even prevent stiffening of the actin cytoskeleton. We propose that these cellular characteristics delay tissue dysfunction, disease, and death in long-lived dog breeds, contributing to canine aging diversity.

The timing of the transition from mortality compression to mortality delay in Europe, Japan and the United States

Previous research found evidence for a transition from mortality compression (declining lifespan variability) to mortality delay (increasing ages at death) in low-mortality countries.We specifically assessed the year at which increases in life expectancy at birth transitioned from being predominantly due to mortality compression to being predominantly due to mortality delay in 26 European countries, Japan, and the United States of America (USA), 1950–2014.To unsmoothed age- and sex-specific death rates from the Human Mortality Database, we applied the CoDe (compression and delay) mortality model.Among women, the transition first occurred in the USA around 1950, then in North-Western Europe (1955–1970) and Southern Europe (1970–1975), and still later in Eastern Europe. Among men, the transition occurred about 10 years later and is still incomplete in Eastern Europe. We identified four stages: (1) predominance of compression mainly due to mortality declines at young ages, (2) declining importance of mortality compression due to the decreasing impact of mortality declines at young ages, (3) delay becomes predominant due to the increasing impact of mortality delay and the counterbalancing effects of mortality compression/expansion at different ages, and (4) strong predominance of delay accompanied by strong adult mortality declines and declining compression at old ages.Our results suggest that life expectancy and maximum lifespan will increase further. With mortality delay, premature mortality and old-age mortality are shifting towards older ages.

Indirect assortative mating for human disease and longevity.

Phenotypic correlations among partners for traits such as longevity or late-onset disease have been found to be comparable to phenotypic correlations in first-degree relatives. How these correlations arise in late life is poorly understood. Here we introduce a novel paradigm to establish the presence of indirect assortment on factors correlated across generations, by examining correlations between parents of couples, i.e., in-laws. Using correlations in additive genetic values we further corroborate the presence of indirect assortment on heritable factors. Specifically, using couples from the UK Biobank cohort, we show that longevity and disease history of the parents of White British couples are correlated, with correlations of up to 0.09. The correlations in parental longevity are replicated in the FamiLinx cohort, a larger and geographically more diverse historical ancestry dataset spanning a broader time frame. These correlations in parental longevity significantly (pval < 0.0093 for all pairs of parents) exceed what would be expected due to variations in lifespan based on year and location of birth. For cardiovascular diseases, in particular hypertension, we find significant correlations (r = 0.028, pval = 0.005) in genetic values among partners, supporting a model where partners assort for risk factors to some extent genetically correlated with cardiovascular disease. Partitioning the relative importance of indirect assortative mating and shared common environment will require large, well-characterized longitudinal cohorts aimed at understanding phenotypic correlations among none-blood relatives. Identifying the factors that mediate indirect assortment on longevity and human disease risk will help to unravel factors affecting human disease and ultimately longevity.