Immunosenescence profiles of lymphocyte compartments and multiple long-term conditions (multimorbidity) in very old adults: The Newcastle 85+ Study.

Immunosenescence, a decline in immune system function, has been linked to several age-related diseases and ageing syndromes. Very old adults (aged ≥ 85 years) live with multiple long-term conditions (MLTC, also known as multimorbidity)-a complex phenomenon of poor health defined by either counts, indices, or patterns, but little is known about the relationship between an ageing immune system and MLTC in this age group. We utilised baseline data from the Newcastle 85+ Study to investigate the associations between previously defined immunosenescence profiles of lymphocyte compartments and MLTC counts and patterns (from 16 chronic diseases/ageing syndromes).

Senolytics and the compression of late-life mortality.

Senescent cells play an important role in mammalian ageing and in the etiology of age-related diseases. Treatment of mice with senolytics - drugs that selectively remove senescent cells - causes an extension of median lifespan but has little effect on maximum lifespan. Postponement of some mortality to later ages, without a corresponding increase in maximum mortality, can be termed 'compression of mortality'.

Aging as a consequence of selection to reduce the environmental risk of dying.

Each animal in the Darwinian theater is exposed to a number of abiotic and biotic risk factors causing mortality. Several of these risk factors are intimately associated with the act of energy acquisition as such and with the amount of reserve the organism has available from this acquisition for overcoming temporary distress. Because a considerable fraction of an individual's lifetime energy acquisition is spent on somatic maintenance, there is a close link between energy expenditure on somatic maintenance and mortality risk.

On the evolution of cellular senescence.

The idea that senescent cells are causally involved in aging has gained strong support from findings that the removal of such cells alleviates many age-related diseases and extends the life span of mice. While efforts proceed to make therapeutic use of such discoveries, it is important to ask what evolutionary forces might have been behind the emergence of cellular senescence, in order better to understand the biology that we might seek to alter. Cellular senescence is often regarded as an anti-cancer mechanism, since it limits the division potential of cells.

Mitochondria in the signaling pathways that control longevity and health span.

Genetic and pharmacological intervention studies have identified evolutionarily conserved and functionally interconnected networks of cellular energy homeostasis, nutrient-sensing, and genome damage response signaling pathways, as prominent regulators of longevity and health span in various species. Mitochondria are the primary sites of ATP production and are key players in several other important cellular processes. Mitochondrial dysfunction diminishes tissue and organ functional performance and is a commonly considered feature of the aging process.

A meta-analysis of genome-wide association studies identifies multiple longevity genes.

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite.

New horizons in the compression of functional decline.

Population ageing, which has come about through the combination of increases in life expectancy, larger post-war cohorts reaching older age and reductions in fertility, is challenging societies and particularly health and care providers, worldwide. In Europe, the USA and Japan, there have been increases in years spent with disability and dependency. The majority of such research, as well as professional health and social care practice, measures loss of functional capability or need for social care, by aggregate disability scores, based around activities of daily living and instrumental activities of daily living.

Predominant Asymmetrical Stem Cell Fate Outcome Limits the Rate of Niche Succession in Human Colonic Crypts.

Stem cell (SC) dynamics within the human colorectal crypt SC niche remain poorly understood, with previous studies proposing divergent hypotheses on the predominant mode of SC self-renewal and the rate of SC replacement. Here we use age-related mitochondrial oxidative phosphorylation (OXPHOS) defects to trace clonal lineages within human colorectal crypts across the adult life-course. By resolving the frequency and size distribution of OXPHOS-deficient clones, quantitative analysis shows that, in common with mouse, long-term maintenance of the colonic epithelial crypt relies on stochastic SC loss and replacement mediated by competition for limited niche access.

Resolving the Enigma of the Clonal Expansion of mtDNA Deletions.

Mitochondria are cell organelles that are special since they contain their own genetic material in the form of mitochondrial DNA (mtDNA). Damage and mutations of mtDNA are not only involved in several inherited human diseases but are also widely thought to play an important role during aging. In both cases, point mutations or large deletions accumulate inside cells, leading to functional impairment once a certain threshold has been surpassed.

Do reef corals age?

Hydra is emerging as a model organism for studies of ageing in early metazoan animals, but reef corals offer an equally ancient evolutionary perspective as well as several advantages, not least being the hard exoskeleton which provides a rich fossil record as well as a record of growth and means of ageing of individual coral polyps. Reef corals are also widely regarded as potentially immortal at the level of the asexual lineage and are assumed not to undergo an intrinsic ageing process. However, putative molecular indicators of ageing have recently been detected in reef corals.

Is There a Link Between Cognitive Reserve and Cognitive Function in the Oldest-Old?

Background: The oldest-old (aged ≥85 years) are the fastest growing age group, with the highest risk of cognitive impairment and dementia. This study investigated whether cognitive reserve applies to the oldest-old. This has implications for cognitive interventions in this age group.

Pervasive gene expression responses to a fluctuating diet in Drosophila melanogaster: The importance of measuring multiple traits to decouple potential mediators of life span and reproduction.

Phenotypic plasticity is an important concept in life-history evolution, and most organisms, including Drosophila melanogaster, show a plastic life-history response to diet. However, little is known about how these life-history responses are mediated. In this study, we compared adult female flies fed an alternating diet (yoyo flies) with flies fed a constant low (CL) or high (CH) diet and tested how whole genome expression was affected by these diet regimes and how the transcriptional responses related to different life-history traits.

Why and how are we living longer?

What is the topic of this review? The reasons for the continuing increase in human life expectancy are examined in the light of progress in understanding the physiological basis of ageing. Prospects for further extending the health span - the period free of age-related disability and disease - are critically assessed. What advances does it highlight? No active programming directly causes ageing, which instead results as a side effect of how evolution optimises the physiological allocation of resources between growth, reproduction and maintenance.

Explaining sex differences in lifespan in terms of optimal energy allocation in the baboon.

We provide a quantitative test of the hypothesis that sex role specialization may account for sex differences in lifespan in baboons if such specialization causes the dependency of fitness upon longevity, and consequently the optimal resolution to an energetic trade-off between somatic maintenance and other physiological functions, to differ between males and females. We present a model in which females provide all offspring care and males compete for access to reproductive females and in which the partitioning of available energy between the competing fitness-enhancing functions of growth, maintenance, and reproduction is modeled as a dynamic behavioral game, with the optimal decision for each individual depending upon his/her state and the behavior of other members of the population. Our model replicates the sexual dimorphism in body size and sex differences in longevity and reproductive scheduling seen in natural populations of baboons.

Longitudinal changes in global and domain specific cognitive function in the very-old: findings from the Newcastle 85+ Study.

Objective: Ageing is associated with changes in cognition in some, but not all domains. In young-old adults, defined as persons aged 65-84 years, baseline cognitive function has been shown to impact on cognitive trajectories. Whether similar patterns occur in the very-old, defined as persons aged 85 years and over, is not known.

Initial level and rate of change in grip strength predict all-cause mortality in very old adults.

Objective: to investigate the associations between initial level and rate of change in grip strength (GS) and all-cause mortality in very old adults (≥85 years) over a 9.6-year follow-up.

Methods: prospective mortality data from 845 participants in the Newcastle 85+ Study were analysed for survival in relation to GS (kg, baseline and 5-year mean change) using Cox proportional hazards models.

Grip strength and inflammatory biomarker profiles in very old adults.

Background: weak grip strength (GS) and chronic inflammation have been implicated in the aetiology of sarcopenia in older adults. Given the interrelationships between inflammatory biomarkers, a summary variable may provide better insight into the relationship between inflammation and muscle strength. This approach has not been investigated in very old adults (aged ≥85) who are at highest risk of muscle weakness.

Vitamin D Status, Muscle Strength and Physical Performance Decline in Very Old Adults: A Prospective Study.

Mixed reports exist about the role of 25-hydroxyvitamin D (25(OH)D) in muscle ageing and there are few prospective studies involving the very old (aged ≥ 85) who are at highest risk of low 25(OH)D, loss of muscle mass and strength, and physical performance decline. In the Newcastle 85+ Study ( = 845), we aimed to determine the association between 25(OH)D season-specific quartiles (hereafter SQ1-SQ4), grip strength (GS) and physical performance decline (Timed Up-and-Go Test, TUG) over 5 years using mixed models. In the time-only models with linear and quadratic slopes, SQ1 and SQ4 of 25(OH)D were associated with weaker GS initially in men (SQ1: β (SE) = -2.

Growing more positive with age: The relationship between reproduction and survival in aging flies.

Populations of laboratory animals that are selected for increased lifespan often show negative correlated responses in early fecundity. However, late fecundity and/or total lifetime fecundity can be higher in the populations selected for increased lifespan. This has been interpreted by some as being at odds with the disposable soma theory, which predicts decreased lifespan to increase total reproductive output.

Prevalence and incidence of sarcopenia in the very old: findings from the Newcastle 85+ Study.

Introduction: Recognition that an older person has sarcopenia is important because this condition is linked to a range of adverse outcomes. Sarcopenia becomes increasingly common with age, and yet there are few data concerning its descriptive epidemiology in the very old (aged 85 years and above). Our aims were to describe risk factors for sarcopenia and estimate its prevalence and incidence in a British sample of the very old.

Predicting Risk of Cognitive Decline in Very Old Adults Using Three Models: The Framingham Stroke Risk Profile; the Cardiovascular Risk Factors, Aging, and Dementia Model; and Oxi-Inflammatory Biomarkers.

Objectives: To examine the Framingham Stroke Risk Profile (FSRP); the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) risk score, and oxi-inflammatory load (cumulative risk score of three blood biomarkers-homocysteine, interleukin-6, C-reactive protein) for associations with cognitive decline using three cohort studies of very old adults and to examine whether incorporating these biomarkers with the risk scores can affect the association with cognitive decline.

Design: Three longitudinal, population-based cohort studies.

Setting: Newcastle-upon-Tyne, United Kingdom; Leiden, the Netherlands; and Lakes and Bay of Plenty District Health Board areas, New Zealand.

Grip Strength Decline and Its Determinants in the Very Old: Longitudinal Findings from the Newcastle 85+ Study.

Background: Weak grip strength (GS) is a key component of sarcopenia and frailty and a powerful predictor of mortality, morbidity and disability. Despite increasing interest in understanding GS across the lifespan, little is known about GS decline in the very old (aged ≥85). We examined trajectories of GS in very old adults and identified the determinants.

Can aging be programmed? A critical literature review.

The evolution of the aging process has long been a biological riddle, because it is difficult to explain the evolution of a trait that has apparently no benefit to the individual. Over 60 years ago, Medawar realized that the force of natural selection declines with chronological age because of unavoidable environmental risks. This forms the basis of the mainstream view that aging arises as a consequence of a declining selection pressure to maintain the physiological functioning of living beings forever.