An explanation of how mutant and wild-type mitochondria might stably co-exist in inherited mitochondrial diseases.

Mitochondria are cellular organelles of crucial relevance for the survival of metazoan organisms. Damage to the mitochondrial DNA can give rise to a variety of mitochondrial diseases and is thought also to be involved in the aging process. The fate of mtDNA mutants is controlled by their synthesis as well as degradation and mathematical models can help to better understand this complex interplay.

No Evidence That Genetic Variation at the Klotho Locus Is Associated With Longevity in Caucasians from the Newcastle 85+ Study and the UK Biobank.

The demographics of Western populations are changing, with an increase in the proportion of older adults. There is evidence to suggest that genetic factors may influence the aging process: studying these may lead to interventions to help individuals live a longer and healthier life. Evidence from several groups indicates that Klotho (KL), a gene encoding a single-pass transmembrane protein that acts as an FGF23 co-receptor, may be associated with longevity and healthy aging.

Frailty, hospital use and mortality in the older population: findings from the Newcastle 85+ study.

Background: Frailty is a significant determinant of health care utilisation and associated costs, both of which also increase with proximity to death. What is not known is how the relationships between frailty, proximity to death, hospital use and costs develop in a population aged 85 years and over.

Methods: This study used data from a prospective observational cohort, the Newcastle 85+ Study, linked with hospital episode statistics and death registrations.

Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study.

Context: Perturbations in thyroid function are common in older individuals but their significance in the very old is not fully understood.

Objective: This study sought to determine whether thyroid hormone status and variation of thyroid hormones within the reference range correlated with mortality and disability in a cohort of 85-year-olds.

Design: A cohort of 85-year-old individuals were assessed in their own homes (community or institutional care) for health status and thyroid function, and followed for mortality and disability for up to 9 years.

Oxidative stress and life histories: unresolved issues and current needs.

Life-history theory concerns the trade-offs that mold the patterns of investment by animals between reproduction, growth, and survival. It is widely recognized that physiology plays a role in the mediation of life-history trade-offs, but the details remain obscure. As life-history theory concerns aspects of investment in the soma that influence survival, understanding the physiological basis of life histories is related, but not identical, to understanding the process of aging.

CMV seropositivity and T-cell senescence predict increased cardiovascular mortality in octogenarians: results from the Newcastle 85+ study.

Although chronic infection with cytomegalovirus (CMV) is known to drive T lymphocytes toward a senescent phenotype, it remains controversial whether and how CMV can cause coronary heart disease (CHD). To explore whether CMV seropositivity or T-cell populations associated with immunosenescence were informative for adverse cardiovascular outcome in the very old, we prospectively analyzed peripheral blood samples from 751 octogenarians (38% males) from the Newcastle 85+ study for their power to predict survival during a 65-month follow-up (47.3% survival rate).

Repeated-sprint cycling does not induce respiratory muscle fatigue in active adults: measurements from the powerbreathe® inspiratory muscle trainer.

This study examined respiratory muscle strength using the POWERbreathe® inspiratory muscle trainer (i.e., 'S-Index') before and after repeated-sprint cycling for comparison with maximal inspiratory pressure (MIP) values obtained during a Mueller maneuver.

Detecting translational regulation by change point analysis of ribosome profiling data sets.

Ribo-Seq maps the location of translating ribosomes on mature mRNA transcripts. While during normal translation, ribosome density is constant along the length of the mRNA coding region, this can be altered in response to translational regulatory events. In the present study, we developed a method to detect translational regulation of individual mRNAs from their ribosome profiles, utilizing changes in ribosome density.

Acute coronary syndrome among older patients: a review.

Ischemic heart disease is the leading cause of mortality worldwide. Due to advances in medicine in the past few decades, life expectancy has increased resulting in an aging population in developed and developing countries. Acute coronary syndrome causes greater morbidity and mortality in this group of older patients, which appears to be due to age-related comorbidities.

The co-occurrence of mtDNA mutations on different oxidative phosphorylation subunits, not detected by haplogroup analysis, affects human longevity and is population specific.

To re-examine the correlation between mtDNA variability and longevity, we examined mtDNAs from samples obtained from over 2200 ultranonagenarians (and an equal number of controls) collected within the framework of the GEHA EU project. The samples were categorized by high-resolution classification, while about 1300 mtDNA molecules (650 ultranonagenarians and an equal number of controls) were completely sequenced. Sequences, unlike standard haplogroup analysis, made possible to evaluate for the first time the cumulative effects of specific, concomitant mtDNA mutations, including those that per se have a low, or very low, impact.

Shared Ageing Research Models (ShARM): a new facility to support ageing research.

In order to manage the rise in life expectancy and the concomitant increased occurrence of age-related diseases, research into ageing has become a strategic priority. Mouse models are commonly utilised as they share high homology with humans and show many similar signs and diseases of ageing. However, the time and cost needed to rear aged cohorts can limit research opportunities.

The association between diagnosed glaucoma and cataract and cognitive performance in very old people: cross-sectional findings from the newcastle 85+ study.

Purpose: Common age-related eye diseases including glaucoma, cataract and age-related macular degeneration (AMD) have been proposed to be associated with dementia. Few studies have examined the relationship between cognition and cataract or glaucoma. We explored the association between cognition and cataract and glaucoma diagnoses in community-dwelling 85-year-olds.

Genome-wide linkage analysis for human longevity: Genetics of Healthy Aging Study.

Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project.

The impact of visual impairment on Mini-Mental State Examination Scores in the Newcastle 85+ study.

Background: cognitive test scores and visual acuity are strongly associated in older people. This may be due to poor vision limiting performance on cognitive tasks specifically requiring vision, or an association between visual and neurodegenerative disorders.

Objective: to explore, using data from the Newcastle 85+ cohort study, the impact of sight impairment (SI) on Mini-Mental State Examination (MMSE) scores and whether reduced scores among SI participants are limited to tasks requiring vision.

Evolution of the mitochondrial fusion-fission cycle and its role in aging.

Mitochondria are organelles of eukaryotic cells that contain their own genetic material and evolved from prokaryotic ancestors some 2 billion years ago. They are the main source of the cell's energy supply and are involved in such important processes as apoptosis, mitochondrial diseases, and aging. During recent years it also became apparent that mitochondria display a complex dynamical behavior of fission and fusion, the function of which is as yet unknown.

Capability and dependency in the Newcastle 85+ cohort study. Projections of future care needs.

Background: Little is known of the capabilities of the oldest old, the fastest growing age group in the population. We aimed to estimate capability and dependency in a cohort of 85 year olds and to project future demand for care.

Methods: Structured interviews at age 85 with 841 people born in 1921 and living in Newcastle and North Tyneside, UK who were permanently registered with participating general practices.

Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease.

Background: Oxidative stress is proposed as an important factor in osteoarthritis (OA).

Objective: To investigate the expression of the three superoxide dismutase (SOD) antioxidant enzymes in OA.

Methods: SOD expression was determined by real-time PCR and immunohistochemistry using human femoral head cartilage.

Feedback between p21 and reactive oxygen production is necessary for cell senescence.

Cellular senescence--the permanent arrest of cycling in normally proliferating cells such as fibroblasts--contributes both to age-related loss of mammalian tissue homeostasis and acts as a tumour suppressor mechanism. The pathways leading to establishment of senescence are proving to be more complex than was previously envisaged. Combining in-silico interactome analysis and functional target gene inhibition, stochastic modelling and live cell microscopy, we show here that there exists a dynamic feedback loop that is triggered by a DNA damage response (DDR) and, which after a delay of several days, locks the cell into an actively maintained state of 'deep' cellular senescence.

The mental wealth of nations.

Countries must learn how to capitalize on their citizens' cognitive resources if they are to prosper, both economically and socially. Early interventions will be key.

A comparison of computerized and pencil-and-paper tasks in assessing cognitive function in community-dwelling older people in the Newcastle 85+ Pilot Study.

Objectives: To compare the acceptability and feasibility of computerized and pencil-and-paper tests of cognitive function in 85-year-old people.

Design: Group comparison of participants randomly allocated to pencil-and-paper (Wechsler Adult Intelligence and Memory Scales) or computerized (Cognitive Drug Research) tests of verbal memory and attention.

Setting: The Newcastle 85+ Pilot Study was the precursor to the Newcastle 85+ Study a United Kingdom Medical Research Council/Biotechnology and Biological Sciences Research Council cohort study of health and aging in the oldest-old age group.