Common mechanisms in aging and obesity are hypothesized to increase susceptibility to neurodegeneration, however, direct evidence in support of this hypothesis is lacking. We therefore performed a cross-sectional analysis of magnetic resonance image-based brain structure on a population-based cohort of healthy adults. Study participants were originally part of the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) and included 527 individuals aged 20-87 years. Cortical reconstruction techniques were used to generate measures of whole-brain cerebral white-matter volume, cortical thickness, and surface area. Results indicated that cerebral white-matter volume in overweight and obese individuals was associated with a greater degree of atrophy, with maximal effects in middle-age corresponding to an estimated increase of brain age of 10 years. There were no similar body mass index-related changes in cortical parameters. This study suggests that at a population level, obesity may increase the risk of neurodegeneration.
- Proceedings of the National Academy of Sciences of the United States of America
- Published about 3 years ago
Antiaging therapies show promise in model organism research. Translation to humans is needed to address the challenges of an aging global population. Interventions to slow human aging will need to be applied to still-young individuals. However, most human aging research examines older adults, many with chronic disease. As a result, little is known about aging in young humans. We studied aging in 954 young humans, the Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades of life. We developed and validated two methods by which aging can be measured in young adults, one cross-sectional and one longitudinal. Our longitudinal measure allows quantification of the pace of coordinated physiological deterioration across multiple organ systems (e.g., pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function). We applied these methods to assess biological aging in young humans who had not yet developed age-related diseases. Young individuals of the same chronological age varied in their “biological aging” (declining integrity of multiple organ systems). Already, before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline and brain aging, self-reported worse health, and looked older. Measured biological aging in young adults can be used to identify causes of aging and evaluate rejuvenation therapies.
Investigating suicides following the death of Robin Williams, a beloved actor and comedian, on August 11th, 2014, we used time-series analysis to estimate the expected number of suicides during the months following Williams' death. Monthly suicide count data in the US (1999-2015) were from the Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research (CDC WONDER). Expected suicides were calculated using a seasonal autoregressive integrated moving averages model to account for both the seasonal patterns and autoregression. Time-series models indicated that we would expect 16,849 suicides from August to December 2014; however, we observed 18,690 suicides in that period, suggesting an excess of 1,841 cases (9.85% increase). Although excess suicides were observed across gender and age groups, males and persons aged 30-44 had the greatest increase in excess suicide events. This study documents associations between Robin Williams' death and suicide deaths in the population thereafter.
Diagnostics of the human ageing process may help predict future healthcare needs or guide preventative measures for tackling diseases of older age. We take a transcriptomics approach to build the first reproducible multi-tissue RNA expression signature by gene-chip profiling tissue from sedentary normal subjects who reached 65 years of age in good health.
Smoking is a major public health problem. As smokers age and die prematurely, the tobacco industry must continue to recruit new, young smokers. Survey data indicate that currently in the UK around 207 000 children aged 11-15 start smoking every year. We used local data on adult smoking rates to apportion national data on child smoking uptake to specific areas. The presentation of data for individual local authorities, which now have responsibility for public health, can be used to focus attention locally. For example, this analysis demonstrates that each day, 67 children, more than two classrooms full, start smoking in London.
Retirement constitutes a major life transition that poses significant challenges to health, with many retirees experiencing a precipitous decline in health status following retirement. We examine the extent to which membership in social groups following retirement determines quality of life and mortality.
In 2012, approximately 40,000 suicides were reported in the United States, making suicide the 10th leading reported cause of death for persons aged ≥16 years (1). From 2000 to 2012, rates of suicide among persons in this age group increased 21.1%, from 13.3 per 100,000 to 16.1 (1). To inform suicide prevention efforts, CDC analyzed suicide by occupational group, by ascribing occupational codes to 12,312 suicides in 17 states in 2012 from the National Violent Death Reporting System (NVDRS) (2). The frequency of suicide in different occupational groups was examined, and rates of suicide were calculated by sex and age group for these categories. Persons working in the farming, fishing, and forestry group had the highest rate of suicide overall (84.5 per 100,000 population) and among males (90.5); the highest rates of suicide among females occurred among those working in protective service occupations (14.1). Overall, the lowest rate of suicide (7.5) was found in the education, training, and library occupational group. Suicide prevention approaches directed toward persons aged ≥16 years that enhance social support, community connectedness, access to preventive services, and the reduction of stigma and barriers to help-seeking are needed.
Aging is the main risk factor for Alzheimer’s disease (AD); however, the aspects of the aging process that predispose the brain to the development of AD are largely unknown. Astrocytes perform a myriad of functions in the central nervous system to maintain homeostasis and support neuronal function. In vitro, human astrocytes are highly sensitive to oxidative stress and trigger a senescence program when faced with multiple types of stress. In order to determine whether senescent astrocytes appear in vivo, brain tissue from aged individuals and patients with AD was examined for the presence of senescent astrocytes using p16(INK4a) and matrix metalloproteinase-1 (MMP-1) expression as markers of senescence. Compared with fetal tissue samples (n = 4), a significant increase in p16(INK4a)-positive astrocytes was observed in subjects aged 35 to 50 years (n = 6; P = 0.02) and 78 to 90 years (n = 11; P<10(-6)). In addition, the frontal cortex of AD patients (n = 15) harbored a significantly greater burden of p16(INK4a)-positive astrocytes compared with non-AD adult control subjects of similar ages (n = 25; P = 0.02) and fetal controls (n = 4; P<10(-7)). Consistent with the senescent nature of the p16(INK4a)-positive astrocytes, increased metalloproteinase MMP-1 correlated with p16(INK4a). In vitro, beta-amyloid 1-42 (Aβ(1-42)) triggered senescence, driving the expression of p16(INK4a) and senescence-associated beta-galactosidase. In addition, we found that senescent astrocytes produce a number of inflammatory cytokines including interleukin-6 (IL-6), which seems to be regulated by p38MAPK. We propose that an accumulation of p16(INK4a)-positive senescent astrocytes may link increased age and increased risk for sporadic AD.
Altered expression of mRNA splicing factors occurs with ageing in vivo and is thought to be an ageing mechanism. The accumulation of senescent cells also occurs in vivo with advancing age and causes much degenerative age-related pathology. However, the relationship between these two processes is opaque. Accordingly we developed a novel panel of small molecules based on resveratrol, previously suggested to alter mRNA splicing, to determine whether altered splicing factor expression had potential to influence features of replicative senescence.
Poor diet quality and insufficient nutrient intake is of particular concern among older adults. The Older Americans Act of 1965 authorizes home-delivered meal services to homebound individuals aged 60 years and older.