Markers Of Longevity Research Articles

Hidden in plain text: Uncovering hidden heterogeneity and social stratification in Ireland AD 1150-1800.

Between the Irish late medieval (AD 1150-c.1550) (LMP) and post-medieval (AD c.1550-1800) (PMP) periods, colonial practices changed land ownership. Contextualizing these periods within a biocultural political economy framework supports increasing social inequality in the PMP, which we expect to be reflected in different skeletal markers of longevity and stress. Therefore, we hypothesized that widespread exposure to stressors and resource deprivation contributed to lower longevity in the PMP compared to the LMP, and that there would be greater variation between sites in the frequency of linear enamel hypoplasias (LEH) in the PMP. We estimated age and counted matched pairs of LEH on 526 adult skeletons from the Irish counties of Dublin, Kildare, Louth, and Meath. Age-at-death was compared through Kaplan-Meier survival functions and non-parametric tests. Linear enamel hypoplasias prevalences were analyzed with Mann-Whitney U tests and Generalized Linear Models. Age-at-death distribution changed between the LMP and PMP for males, with males experiencing an increase in median-age-at-death. The same was untrue for females, who show no changes in median age-at-death. Analysis of LEH frequency per individual showed that variation between sites was significant in the post-medieval period but not in the late medieval period. These results suggest that social organization contributed to embodied health experiences that varied across time periods. Specifically, populations from the PMP appear to have embodied greater social inequality in their more varied susceptibility to stress. Our work demonstrates the strength of pairing historical texts with the analysis of skeletal remains to evaluate the impact of social structures on biological frailty.

Autologous transplantation of green tea epigallocatechin-3-gallate pretreated adipose-derived stem cells increases cardiac regenerative capability through C-X-C motif chemokine receptor 4 expression in the treatment of rats with diabetic cardiomyopathy.

Cardiomyopathy is one of complications related to diabetes. Stem cell transplantation shows potential in diabetic cardiomyopathy treatment. Epigallocatechin-3-gallate (EGCG) is one of the major components found in green tea. Although stem cell transplantation and green tea EGCG supplementation show therapeutic effects on cardiomyopathy, the detailed cellular mechanisms in stem cell transplantation coupled with EGCG treatment remain unclear. This study investigates whether adipose-derived stem cells (ADSC) pretreated with EGCG show better protective effect on diabetic cardiomyopathy than ADSC without EGCG pretreatment. A cell model indicated that ADSC pretreated with EGCG increased cell functions including colony formation, migration and survival markers. All of these functions are blocked by small interfering C-X-C motif chemokine receptor 4 (siCXCR4) administration. These findings suggest that ADSC pretreatment with EGCG increases cell functions through CXCR4 expression. A diabetic animal model was designed to verify the above findings, including Sham, DM (diabetes mellitus), DM+ADSC (DM rats receiving autologous transplantation of ADSC) and DM+E-ADSC (DM rats receiving EGCG pretreated ADSC). Compared to the Sham, we found that all of pathophysiological signalings were activated in the DM group, including functional changes (decrease in ejection fraction and fractional shortening), structural changes (disarray and fibrosis) and molecular changes (increases in apoptotic, fibrotic, hypertrophic markers and decreases in survival and longevity markers). E-ADSC (DM+E-ADSC) transplantation shows significant improvement in the above pathophysiological signalings greater than ADSC (DM+ADSC). Therefore, ADSC pretreated with EGCG may contribute to clinical applications for diabetic patients with cardiomyopathy.

METABOLOMICS OF LONGEVITY AND LIFESPAN

Abstract Serum metabolomics has been an important source of biomarkers of aging and longevity for years. This symposium will bring together investigators from large studies of human longevity to provide an overview of recent discoveries on serum metabolomics of aging and extreme human longevity, their connections to genetic variations, and highlight the challenges of correlating metabolomic profiles of aging in human studies and across multiple species. Dr. Sebastiani will describe results from analyses of serum metabolomics of participants enrolled in the Long Life Family Study, highlight similarities and differences between metabolomic profiles of old age and extreme old age, and some connections with genetics of extreme human longevity. Dr. Rappaport will connect specific variations of the APOE alleles to metabolomic profiles and describe a possible role of bioenergetics pathways in mediating the effect of APOE to longevity and resistance to Alzheimer’s disease. Dr. Monti will expand the characterization of metabolomics of aging and extreme human longevity in a large metabolomic study of very old centenarians by using traditional statistical analyses and novel machine learning techniques. His analysis identifies rich signatures of aging and longevity that include well known metabolites and point to bile acids and several classes of steroids as important marker of longevity. Analytical innovations will be taken further by Dr. Schork who will introduce a novel approach based on distance of profiles to analyze multiple metabolites simultaneously and show the value of this approach to analyze metabolomic profiles of maximum lifespan across multiple species. This is a Geroscience Interest Group Sponsored Symposium.

Proteomic signature profiling in the cortex of dairy cattle unravels the physiology of brain aging.

Aging is a physiological process occurring in all living organisms. It is characterized by a progressive deterioration of the physiological and cognitive functions of the organism, accompanied by a gradual impairment of mechanisms involved in the regulation of tissue and organ homeostasis, thus exacerbating the risk of developing pathologies, including cancer and neurodegenerative disorders. In the present work, for the first time, the influence of aging has been investigated in the brain cortex of the Podolica cattle breed, through LC-MS/MS-based differential proteomics and the bioinformatic analysis approach (data are available via ProteomeXchange with identifier PXD044108), with the aim of identifying potential aging or longevity markers, also associated with a specific lifestyle. We found a significant down-regulation of proteins involved in cellular respiration, dendric spine development, synaptic vesicle transport, and myelination. On the other hand, together with a reduction of the neurofilament light chain, we observed an up-regulation of both GFAP and vimentin in the aged samples. In conclusion, our data pave the way for a better understanding of molecular mechanisms underlying brain aging in grazing cattle, which could allow strategies to be developed that are aimed at improving animal welfare and husbandry practices of dairy cattle from intensive livestock.

Integrated analysis of proteomics, epigenomics and metabolomics data revealed divergent pathway activation patterns in the recent versus chronic post-traumatic stress disorder

Metabolomics, proteomics and DNA methylome assays, when done in tandem from the same blood sample and analyzed together, offer an opportunity to evaluate the molecular basis of post-traumatic stress disorder (PTSD) course and pathogenesis. We performed separate metabolomics, proteomics, and DNA methylome assays on blood samples from two well-characterized cohorts of 159 active duty male participants with relatively recent onset PTSD (<1.5 years) and 300 male veterans with chronic PTSD (>7 years). Analyses of the multi-omics datasets from these two independent cohorts were used to identify convergent and distinct molecular profiles that might constitute potential signatures of severity and progression of PTSD and its comorbid conditions. Molecular signatures indicative of homeostatic processes such as signaling and metabolic pathways involved in cellular remodeling, neurogenesis, molecular safeguards against oxidative stress, metabolism of polyunsaturated fatty acids, regulation of normal immune response, post-transcriptional regulation, cellular maintenance and markers of longevity were significantly activated in the active duty participants with recent PTSD. In contrast, we observed significantly altered multimodal molecular signatures associated with chronic inflammation, neurodegeneration, cardiovascular and metabolic disorders, and cellular attritions in the veterans with chronic PTSD. Activation status of signaling and metabolic pathways at the early and late timepoints of PTSD demonstrated the differential molecular changes related to homeostatic processes at its recent and multi-system syndromes at its chronic phase. Molecular alterations in the recent PTSD seem to indicate some sort of recalibration or compensatory response, possibly directed in mitigating the pathological trajectory of the disorder.

Linking Pensions to Life Expectancy: Tackling Conceptual Uncertainty through Bayesian Model Averaging

Linking pensions to longevity developments at retirement age has been one of the most common policy responses of pension schemes to aging populations. The introduction of automatic stabilizers is primarily motivated by cost containment objectives, but there are other dimensions of welfare restructuring in the politics of pension reforms, including recalibration, rationalization, and blame avoidance for unpopular policies that involve retrenchments. This paper examines the policy designs and implications of linking entry pensions to life expectancy developments through sustainability factors or life expectancy coefficients in Finland, Portugal, and Spain. To address conceptual and specification uncertainty in policymaking, we propose and apply a Bayesian model averaging approach to stochastic mortality modeling and life expectancy computation. The results show that: (i) sustainability factors will generate substantial pension entitlement reductions in the three countries analyzed; (ii) the magnitude of the pension losses depends on the factor design; (iii) to offset pension cuts and safeguard pension adequacy, individuals will have to prolong their working lives significantly; (iv) factor designs considering cohort longevity markers would have generated higher pension cuts in countries with increasing life expectancy gap.

Deep longitudinal phenotyping of wearable sensor data reveals independent markers of longevity, stress, and resilience.

Biological age acceleration (BAA) models based on blood tests or DNA methylation emerge as a de facto standard for quantitative characterizations of the aging process. We demonstrate that deep neural networks trained to predict morbidity risk from wearable sensor data can provide a high-quality and cheap alternative for BAA determination. The GeroSense BAA model was trained and validated using steps per minute recordings from 103,830 one-week long and 2,599 of up to 2 years-long longitudinal samples and exhibited a superior association with life-expectancy over the average number of steps per day in, e.g., groups stratified by professional occupations. The association between the BAA and effects of lifestyles, the prevalence of future incidence of diseases was comparable to that of BAA from models based on blood test results. Wearable sensors let sampling of BAA fluctuations at time scales corresponding to days and weeks and revealed the divergence of organism state recovery time (resilience) as a function of chronological age. The number of individuals suffering from the lack of resilience increased exponentially with age at a rate compatible with Gompertz mortality law. We speculate that due to the stochastic character of BAA fluctuations, its mean and auto-correlation properties together comprise the minimum set of biomarkers of aging in humans.

Antioxidant and Anti-Inflammaging Ability of Prune (Prunus Spinosa L.) Extract Result in Improved Wound Healing Efficacy.

Prunus spinosa L. fruit (PSF) ethanol extract, showing a peculiar content of biologically active molecules (polyphenols), was investigated for its wound healing capacity, a typical feature that declines during aging and is negatively affected by the persistence of inflammation and oxidative stress. To this aim, first, PSF anti-inflammatory properties were tested on young and senescent LPS-treated human umbilical vein endothelial cells (HUVECs). As a result, PSF treatment increased miR-146a and decreased IRAK-1 and IL-6 expression levels. In addition, the PSF antioxidant effect was validated in vitro with DPPH assay and confirmed by in vivo treatments in C. elegans. Our findings showed beneficial effects on worms’ lifespan and healthspan with positive outcomes on longevity markers (i.e., miR-124 upregulation and miR-39 downregulation) as well. The PSF effect on wound healing was tested using the same cells and experimental conditions employed to investigate PSF antioxidant and anti-inflammaging ability. PSF treatment resulted in a significant improvement of wound healing closure (ca. 70%), through cell migration, both in young and older cells, associated to a downregulation of inflammation markers. In conclusion, PSF extract antioxidant and anti-inflammaging abilities result in improved wound healing capacity, thus suggesting that PSF might be helpful to improve the quality of life for its beneficial health effects.

Adipose derived mesenchymal stem cells along with Alpinia oxyphylla extract alleviate mitochondria-mediated cardiac apoptosis in aging models and cardiac function in aging rats

Ethnopharmacological relevanceThe Fructus (Alpinia oxyphylla MIQ) known as Yi Zhi Ren in Chinese medicine has been used as a food and herbal medicinal substance in China for centuries; in the year 2015 Chinese Pharmacopoeia Commission reported water extracts of Alpinia oxyphyllae Fructus (AoF) as a popular medication for aging-related diseases in the form of tonic, aphrodisiac, and health-care food in south China.Aim of the study: Adipose mesenchymal stem cells are physiologically and therapeutically associated with healthy vascular function and cardiac health. However aging conditions hinder stem cell function and increases the vulnerability to cardiovascular diseases. In this study, the effect of the anti-aging herbal medicine AoF to enhance the cardiac restorative function of adipose-derived mesenchymal stem cells (ADMSCs) in aging condition was investigated. Materials and methodsLow dose (0.1 μM) Doxorubicin and D-galactose (150 mg/kg/day for 8 weeks) were used to respectively induce aging in vitro and in vivo. For In vivo studies, 20 week old WKY rats were divided into Control, Aging induced (AI), AI + AoF, AI + ADMSC, AI + AoF Oral + ADMSC, and AI + AoF treated ADMSC groups. AoF (100 mg/kg/day) was administered orally and ADMSCs (1 × 106 cells) were injected (IV). ResultsAoF preconditioned ADMSC showed reduction in low dose Dox induced mitochondrial apoptosis and improved DNA replication in H9c2 cardiomyoblasts. In vivo experiments confirmed that both a combined treatment with AoF-ADMSCs and with AoF preconditioned ADMSCs reduced aging associated cardiac damages which was correlated with reduction in apoptosis and expression of senescence markers (P21 and β-gal). Survival and longevity markers were upregulated up on combined administration of AoF and ADMSCs. The cardiac performance of the aging-induced rats was improved significantly in the treatment groups. AoF along with ADMSCs might activate paracrine factors to restore the performance of an aging heart. ConclusionHence, we propose that ADMSCs combined with AoF have promising therapeutic properties in the treatment of healthy aging heart.

20-year Trends Of Coronary Calcium Scores And Cardiovascular Risk Factors In Beach Cities/ Certified Blue Zones Of California: Impact Of Blue Zones Project?

Introduction: Blue Zones Project (BZP) adopts Power9 principles of well-being from places around the world where people consistently live over 100 years old. BZP was introduced in Beach Cities of CA in 2012, through implementation of policy and environmental changes including smoking ban, mindfulness community groups, bike/walk policies, curated grocery stores - with the goal “to make the healthy choice the easy choice for millions of Americans” and subsequently, increase life expectancy. Coronary Calcium (CAC) scores of zero can serve as surrogate markers of longevity. Impact of BZP on cardiovascular health is unknown.

The Role of Matrix Metalloproteinases (MMP-2 and MMP-9) in Ageing and Longevity: Focus on Sicilian Long-Living Individuals (LLIs).

Extracellular matrix metalloproteinases (MMPs) are a group of proteins that activate substrates by enzymatic cleavage and, on the basis of their activities, have been demonstrated to play a role in ageing. Thus, in order to gain insight into the pathophysiology of ageing and to identify new markers of longevity, we analysed the activity levels of MMP-2 and MMP-9 in association with some relevant haematochemical parameters in a Sicilian population, including long-living individuals (LLIs, ≥95 years old). A cohort of 154 healthy subjects (72 men and 82 women) of different ages (age range 20-112) was recruited. The cohort was divided into five subgroups: the first group with subjects less than 40 years old, the second group ranging from 40 to 64 years old, the third group ranging from 65 to 89 years old, the fourth group ranging from 90 to 94 years old, and the fifth group with subjects more than 95 years old. A relationship was observed between LLIs and MMP-2, but not between LLIs and MMP-9. However, in the LLI group, MMP-2 and MMP-9 values were significantly correlated. Furthermore, in LLIs, we found a positive correlation of MMP-2 with the antioxidant catabolite uric acid and a negative correlation with the inflammatory marker C-reactive protein. Finally, in LLIs MMP-9 values correlated directly both with cholesterol and with low-density lipoproteins. On the whole, our data suggest that the observed increase of MMP-2 in LLIs might play a positive role in the attainment of longevity. This is the first study that shows that serum activity of MMP-2 is increased in LLIs as compared to younger subjects. As far as we are concerned, it is difficult to make wide-ranging conclusions/assumptions based on these observations in view of the relatively small sample size of LLIs. However, this is an important starting point. Larger-scale future studies will be required to clarify these findings including the link with other systemic inflammatory and antioxidant markers.

The Year of the Honey Bee (Apis mellifera L.) with Respect to Its Physiology and Immunity: A Search for Biochemical Markers of Longevity.

It has been known for many years that in temperate climates the European honey bee, Apis mellifera, exists in the form of two distinct populations within the year, short-living summer bees and long-living winter bees. However, there is only limited knowledge about the basic biochemical markers of winter and summer populations as yet. Nevertheless, the distinction between these two kinds of bees is becoming increasingly important as it can help beekeepers to estimate proportion of long-living bees in hives and therefore in part predict success of overwintering. To identify markers of winter generations, we employed the continuous long-term monitoring of a single honey bee colony for almost two years, which included measurements of physiological and immunological parameters. The results showed that the total concentration of proteins, the level of vitellogenin, and the antibacterial activity of haemolymph are the best three of all followed parameters that are related to honey bee longevity and can therefore be used as its markers.

Gender-Specific Differences in Concentrations of Biochemical Parameters in Persons over the Age of 90.

The ageing process is a phenomenon leading to an emergence of a web of interrelated biological processes producing significant changes in the human body. The aim of the paper was to analyse gender-specific differences with regard to selected biochemical parameters in longevity. The study was conducted in Poland in 2017. The study population comprised of long-lived individuals, both living at home and staying at residential care homes. There were 90 people of both genders (69 women and 21 men) aged between 90 and 103 years (mean = 92.36; SD = 2.98). The biochemical markers of longevity in the studied patients were identified by assessing their pro-inflammatory and anti-inflammatory status in various metabolic aspects. The analysis of biochemical variables revealed numerous statistically significant differences, both in the study group as a whole and between the genders. The ageing process is extremely complex, but understanding it will allow for a real intervention in life extension. Research into the processes involved in ageing and longevity will enable a better understanding of the mechanisms responsible for them, and to enjoy those processes in good health.

Psychological markers of longevity in Sardinian centenarians: the impact of developmental factors and social desirability.

A body of research documented that the study of mental health of the oldest individuals may contribute to understand the psychological characteristics of longevity. This study had two related aims. First, to fully characterize the psychological health of Sardinian elders in the very late adult span. Second, to determine the psychological health of long-lived individuals (i.e., centenarians) from this population. Three gender-matched age groups (octogenarian, nonagenarian, centenarian) of cognitively healthy, community dwelling adults were recruited in Sardinia, an Italian island characterized by higher levels of longevity. Comparisons of total and sub-scale levels of psychological well-being and depressive symptomatology were made while controlling for social desirability. There were few differences in any index of psychological health between the groups; only a decrease in the coping strategies sub-scale of psychological well-being was observed between the centenarians and the octogenarians. Social desirability was differentially associated with specific dimensions of depressive symptoms and psychological well-being. These findings highlight that there is minimal age-related decline in the psychological health of a longevous population, even among its very oldest members. The present outcomes suggest that older Sardinians represent an advantageous population for the investigation of the psychological markers of longevity, since they demonstrate positive adaptation to the challenges (e.g., changes related to their social network) of very late adulthood.

Which type of exercise keeps you young?

Robust epidemiological evidence exists that lifelong regular exercise contributes to longevity. The aim of this review is to discuss recent findings regarding, which dose and type of physical activity promotes a long healthy life, free of disease. Meeting the currently recommended amounts of leisure time physical aerobic activity of moderate intensity of at least 150 min/week provides most of the longevity benefit. However, a higher duration and intensity augments the beneficial effect on cardiovascular health and metabolism. Performing three to five times the recommended physical activity minimum reaches the maximal longevity benefit, that can be achieved. Although it is not dangerous to perform even higher amounts of exercise, the benefit may decrease. A high maximal oxygen uptake in mid-life is a strong marker of longevity, whereas muscle mass is a critical prognostic factor in aging and cancer. Exercise training above the public health recommendations provides additional benefits regarding disease protection and longevity. Endurance exercise, including high-intensity training to improve cardiorespiratory fitness promotes longevity and slows down aging. Strength training should be added to slow down loss of muscle mass, associated with aging and disease.

In Memoriam: Michael Cooper (1930–2018)

In MemoriamMichael Cooper (1930–2018) Kate Wildman Nakai Michael Cooper, editor of Monumenta Nipponica from 1972 to 1997, died peacefully in Honolulu, Hawaii, on 31 March 2018 after a short illness. He was just a month short of his eighty-eighth birthday. In Japan, as he would undoubtedly point out were he writing this piece, this is a felicitous marker of longevity. Michael was born in London on 25 April 1930. He paid great attention to people’s birthdays and to remembering them with a card. Perhaps as a gentle reproach to those less conscientious and kind about such matters than he, on occasion he remarked that his birthday could be easily recalled because it was the same as Oliver Cromwell’s. After completing his secondary education at the Jesuit school Beaumont College, Old Windsor, Michael entered the Society of Jesus in September 1948. He spent the next six years at Jesuit training centers in the United Kingdom and Spain. The time spent in Spain likely fostered the skills in Spanish and Portuguese that he later would put to use in his research on the Western encounter with Japan in the sixteenth and early seventeenth centuries. This stage of his education concluded with a year of philosophical studies at Manresa College, London, in 1953–1954. The following year Michael was sent to Japan, where he embarked on two years’ study of Japanese at the Jesuit language program in Taura, Yokosuka. The school’s proximity to Kamakura encouraged exploration of that city’s temples and other sites and led him to become, in the words of the blurb to his historical guidebook Exploring Kamakura: A Guide for the Curious Traveler (Weatherhill, 1979), a “confirmed Kamakura buff.” The same blurb reports that the guidebook is based on “notes taken during his student days.” Later he would often enjoy leading friends and visitors on personal tours to his favorite spots. Click for larger view View full resolution In the classroom at Sophia (late 1950s). Sophia University Archives. Michael spent two further years in Japan teaching English at Sophia University and working in the university’s public relations office before going back to the UK in 1959 for four years of theological studies at Heythrop College, then located near Oxford. Presumably it was during this time that the general course of his subsequent academic path was set. He once mentioned that Pedro Arrupe, later superior general [End Page 179] of the Society of Jesus and from 1958 to 1965 head of its Japan Province, instructed him to obtain a degree in anthropology with the idea that he would eventually return to Tokyo and take up the editorship of MN. In 1963 Michael entered the two-year program in social anthropology at the University of Oxford, at the time the usual preliminary step for pursuing an advanced degree there in the subject. Having obtained a diploma in social anthropology, he proceeded to the doctoral course and was awarded his doctorate in 1969. Oxford was a center of the “cultural translation” approach to social anthropology associated with E. E. Evans-Pritchard, with whom Michael studied. Evans-Pritchard emphasized the importance of immersing oneself in the language and culture of the society that was the object of one’s research. Only in this way could one grasp what things meant in their original context and, on that basis, translate them accurately into the mode of understanding basic to one’s own language. Michael would adopt cultural translation as both a topic to investigate and a principle to apply. The core of Michael’s dissertation was a translation from the Portuguese into English of the account of Japanese life and customs compiled by the Jesuit missionary João Rodrigues in the first decades of the seventeenth century. The research that Michael did for his dissertation was subsequently published in three forms. In 1973 he brought out a somewhat abridged version of Rodrigues’s lengthy work as This Island of Japon: João Rodrigues’ Account of 16th-Century Japan (Kodansha International). A complete annotated translation eventually appeared under a slightly revised title as João Rodrigues’s Account of Sixteenth-Century Japan (The Hakluyt Society, 2001). Michael produced...

Professional Athletes’ Return to Play and Performance after Achilles Tendon Ruptures

Category: Sports Introduction/Purpose: The majority of Achilles tendon ruptures are sports-related. A significant decrease in return to play, playing time, and performance has been shown in National Basketball Association (NBA) players who sustained a complete Achilles tendon rupture requiring surgical repair. However, no study to date has examined and compared the impact on performance and return to play across multiple professional sports. Methods: Publicly available records yielded a list of NBA, National Football League (NFL), Major League Baseball (MLB), and National Hockey League (NHL) athletes who suffered Achilles tendon ruptures requiring surgical repair from 1989-2013. Demographic information and performance-related statistics were recorded from public sports statistics websites. The primary outcome of this study was the proportion of games played post- vs. pre-injury. Secondary markers of longevity were minutes played for NBA, games started for NFL, and innings played in field for MLB. Inclusion criteria included individuals in the NBA, NFL, MLB, and NHL with professional experience for at least 2 years before and after sustaining a primary Achilles tendon rupture requiring surgical repair. A matched control was selected for all returning players by identifying athletes with similar playing position, number of seasons played, and career performance statistics. The study was powered to detect a 15% difference in games played between ruptures and controls. Results: Of 100 athletes initially screened for the study, 43 met the inclusion criteria. Others were excluded for not completing at least 2 seasons pre- (n=16) or post-injury (n=32), or having a confounding injury (n=9). Athletes on average played 75.4% (p &lt; 0.001) and 81.9% (p=0.002) of the games played the season prior to injury at 1 and 2 years post-injury, respectively. Other markers of longevity were also significantly decreased in athletes at 1 and 2 years post-injury (p &lt; 0.001). Athletes also performed worse, with post-injury performances equivalent to 74.8% of pre-injury performance at 1 year (p=0.001) and 77.7% at 2 years (p &lt; 0.001). Compared to controls, athletes with Achilles injuries played fewer games (p &lt; 0.001) and had decreased longevity (p=0.025), and performance statistics (p &lt; 0.001) at 1 year, but not 2 years after injury. Conclusion: An Achilles rupture is a devastating injury with many athletes unable to return to play. Further, athletes who managed to play for 2 years after injury play significantly fewer games, and experience significant decreases in secondary measures of longevity and performance metrics. Compared to controls, however, only the 1-year post-injury longevity and performance statistics were significantly worse. This implies a bimodal distribution of successful return to play: a significant portion of athletes undergoing repair never return to their prior level of competition, but those that do can often perform at a level commensurate with non-injured controls after 2 years.

Telomere length is longer in women with late maternal age.

Maternal age at birth of last child has been associated with maternal longevity. The aim of this study was to determine whether older women with a history of late maternal age at last childbirth had a longer leukocyte telomere length than those with maternal age at last childbirth of 29 years or less. A nested case control study was conducted using data from the Long Life Family Study. Three hundred eighty-seven women who gave birth to at least one child and lived to the top fifth percentile of their birth cohort, or died before the top fifth percentile of their birth cohort died, but were at least 70 years old, were studied. Logistic regression models using generalized estimating equations were used to determine the association between tertiles of telomere length and maternal age at last childbirth, adjusting for covariates. Age at birth of the last child was significantly associated with leukocyte telomere length. Compared with women who gave birth to their last child before the age of 29, women who were past the age of 33 when they had their last child were two to three times more likely to have leukocyte telomere length in the second and third tertiles than in the first tertile. These findings show an association between longer leukocyte telomere length and a later maternal age at birth of last child, suggesting that extended maternal age at last childbirth may be a marker for longevity.

Ivabradine in Patients with Stable Coronary Artery Disease: A Rationale for Use in Addition to and Beyond Percutaneous Coronary Intervention.

Heart rate is an established prognostic marker for longevity and is an important contributor in the pathophysiology of various cardiovascular diseases, including ischemic heart disease and heart failure. Most ischemic episodes are triggered by an increase in heart rate, which causes an imbalance between myocardial oxygen delivery and consumption. In addition, increased heart rate is a modifiable risk factor for chronic heart failure. Ivabradine, an inhibitor of If ion channels, is an approved second-line anti-ischemic drug for the treatment of angina. Ivabradine has been shown to decrease the risk of hospitalization in patients with chronic heart failure who were previously treated with β-blockers, renin-angiotensin system blockers or mineralocorticoid receptor antagonists. This review describes the rationale for the pathophysiological and clinical use of ivabradine as an anti-ischemic agent in patients with stable coronary disease and highlights its benefits and drawbacks compared with other first- and second-line anti-anginal drugs. The review also highlights the role of ivabradine as a treatment for patients with high-risk coronary artery disease in whom first-line anti-anginal drugs are insufficient or inadequate and percutaneous coronary intervention is contraindicated or revascularization is incomplete or unsuitable.

Contribution of genetic polymorphisms on functional status at very old age: A gene-based analysis of 38 genes (311 SNPs) in the oxidative stress pathway

Preservation of functional ability is a well-recognized marker of longevity. At a molecular level, a major determinant of the physiological decline occurring with aging is the imbalance between production and accumulation of oxidative damage to macromolecules, together with a decreased efficiency of stress response to avoid or repair such damage. In this paper we investigated the association of 38 genes (311 SNPs) belonging to the pro–antioxidant pathways with physical and cognitive performances, by analyzing single SNP and gene-based associations with Hand Grip strength (HG), Activities of Daily Living (ADL), Walking Speed (WS), Mini Mental State Examination (MMSE) and Composite Cognitive Score (CCS) in a Cohort of 1089 Danish nonagenarians. Moreover, for each gene analyzed in the pro–antioxidant pathway, we tested the influence on longitudinal survival.In the whole sample, nominal associations were found for TXNRD1 variability with ADL and WS, NDUFS1 and UCP3 with HG and WS, GCLC and UCP2 with WS (p<0.05). Stronger associations although not holding the multiple comparison correction, were observed between MMSE and NDUFV1, MT1A and GSTP1 variability (p<0.009). Moreover, we found that association between genetic variability in the pro–antioxidant pathway and functional status at old age is influenced by sex. In particular, most significant associations were observed in nonagenarian females, between HG scores and GLRX and UCP3 variability, between ADL levels and TXNRD1, MMSE and MT1A genetic variability. In males, a borderline statistically significant association with ADL level was found for UQCRFS1 gene.Nominally significant associations in relation to survival were found in the female sample only with SOD2, NDUFS1, UCP3 and TXNRD1 variability, the latter two confirming previous observations reported in the same cohort. Overall, our work supports the evidence that genes belonging to the pro–anti-oxidant pathway are able to modulate physical and cognitive performance after the ninth decade of life, finally influencing extreme survival.