Why Don't CD8+ T Cells Reduce the Lifespan of SIV-Infected Cells In Vivo?

In January 2010 two groups independently published the observation that the depletion of CD8+ cells in SIV-infected macaques had no detectable impact on the lifespan of productively infected cells. This unexpected observation led the authors to suggest that CD8+ T cells control SIV viraemia via non-lytic mechanisms. However, a number of alternative plausible explanations, compatible with a lytic model of CD8+ T cell control, were proposed. This left the field with no consensus on how to interpret these experiments and no clear indication whether CD8+ T cells operated primarily via a lytic or a non-lytic mechanism. The aim of this work was to investigate why CD8+ T cells do not appear to reduce the lifespan of SIV-infected cells in vivo

Can Non-lytic CD8+T Cells Drive HIV-1 Escape?

The CD8+ T cell effector mechanisms that mediate control of HIV-1 and SIV infections remain poorly understood. Recent work suggests that the mechanism may be primarily non-lytic. This is in apparent conflict with the observation that SIV and HIV-1 variants that escape CD8+ T cell surveillance are frequently selected. Whilst it is clear that a variant that has escaped a lytic response can have a fitness advantage compared to the wild-type, it is less obvious that this holds in the face of non-lytic control where both wild-type and variant infected cells would be affected by soluble factors. In particular, the high motility of T cells in lymphoid tissue would be expected to rapidly destroy local effects making selection of escape variants by non-lytic responses unlikely. The observation of frequent HIV-1 and SIV escape poses a number of questions. Most importantly, is the consistent observation of viral escape proof that HIV-1- and SIV-specific CD8+ T cells lyse infected cells or can this also be the result of non-lytic control? Additionally, the rate at which a variant strain escapes a lytic CD8+ T cell response is related to the strength of the response. Is the same relationship true for a non-lytic response? Finally, the potential anti-viral control mediated by non-lytic mechanisms compared to lytic mechanisms is unknown. These questions cannot be addressed with current experimental techniques nor with the standard mathematical models. Instead we have developed a 3D cellular automaton model of HIV-1 which captures spatial and temporal dynamics. The model reproduces in vivo HIV-1 dynamics at the cellular and population level. Using this model we demonstrate that non-lytic effector mechanisms can select for escape variants but that outgrowth of the variant is slower and less frequent than from a lytic response so that non-lytic responses can potentially offer more durable control

Positive views of aging reduce risk of developing later-life obesity

The obesity epidemic among older adults is expected to continue increasing unless public-health efforts address this age group. Yet, little is known about psychosocial determinants of obesity that relate specifically to older persons. In this study, we investigated for the first time whether self-perceptions of aging (SPA), defined as beliefs about oneself as an older person that are assimilated from society, relate to new cases of obesity. This seemed plausible because older persons who report more-positive SPA tend to engage in more health-promoting behaviors. Our sample consisted of 5702 Americans in the nationally representative Health and Retirement Study who were aged 60 years or older and not obese at baseline. The participants were followed from 2008 to 2014. As predicted, older persons with more-positive SPA, compared to those with more-negative SPA, were significantly less likely to become obese over the next 6 years, after adjusting for relevant covariates. For example, according to our model, a participant with the most-positive SPA score was 27% less likely to become obese than a same-aged peer with an average score on the SPA measure. These findings suggest that interventions aimed at reducing the prevalence of obesity in later life could benefit from targeting SPA. Keywords: Ageism, Stereotyping, Healthy aging, Obesity, Self perceptions of aging, Views of aging, Behaviors, Preventive healt

Impact of structural ageism on greater violence against older persons: a cross-national study of 56 countries

Objective To determine the association between country-level structural ageism and prevalence of violence against older persons.Design Country-level ecological study.Setting Structural ageism data were drawn from the nationally representative World Values Survey 2010–2014 (WVS), global databases from the WHO, United Nations and the World Bank. Violence data were based on the Global Burden of Diseases (GBD) study 2017.Participants Analysis of 56 countries that represented 63.1% of the world’s ageing population aged 60 and over across all six of WHO regions.Exposure Structural ageism, following established structural stigma measures, consisted of two components: (1) discriminatory national policies related to older persons’ economic, social, civil and political rights, based on the four core components of human rights protection in Madrid International Plan of Action on Aging and (2) prejudicial social norms against older persons, measured by negative attitudes toward older persons in 56 national polls in WVS aggregated to country-level. These components were z scored and combined such that higher score indicated greater structural ageism.Main outcomes and measures Prevalence rates of violence per 100 000 persons aged 70 and over in each country was based on extensive epidemiological surveillance data, survey, clinical data and insurance claims in GBD and compiled by the Institute of Health Metrics and Evaluation, University of Washington.Results There was a wide variation in levels of structural ageism across countries. As predicted, structural ageism was significantly associated with the prevalence rates of violence in multivariate models (β=205.7, SE=96.3, p=0.03), after adjusting for relevant covariates. Sensitivity analyses supported the robustness of our findings. That is, structural ageism did not predict other types of violence and other types of prejudice did not predict violence against older persons.Conclusions This study provides the first evidence of the association between higher structural ageism and greater violence against older persons across countries

Positive age beliefs protect against dementia even among elders with high-risk gene.

One of the strongest risk factors for dementia is the ε4 variant of the APOE gene. Yet, many who carry it never develop dementia. The current study examined for the first time whether positive age beliefs that are acquired from the culture may reduce the risk of developing dementia among older individuals, including those who are APOE ε4 carriers. The cohort consisted of 4,765 Health and Retirement Study participants who were aged 60 or older and dementia-free at baseline. As predicted, in the total sample those with positive age beliefs at baseline were significantly less likely to develop dementia, after adjusting for relevant covariates. Among those with APOE ε4, those with positive age beliefs were 49.8% less likely to develop dementia than those with negative age beliefs. The results of this study suggest that positive age beliefs, which are modifiable and have been found to reduce stress, can act as a protective factor, even for older individuals at high risk of dementia

Global reach of ageism on older persons' health: A systematic review.

OBJECTIVE:Although there is anecdotal evidence of ageism occurring at both the structural level (in which societal institutions reinforce systematic bias against older persons) and individual level (in which older persons take in the negative views of aging of their culture), previous systematic reviews have not examined how both levels simultaneously influence health. Thus, the impact of ageism may be underestimated. We hypothesized that a comprehensive systematic review would reveal that these ageism levels adversely impact the health of older persons across geography, health outcomes, and time. METHOD:A literature search was performed using 14 databases with no restrictions on region, language, and publication type. The systematic search yielded 13,691 papers for screening, 638 for full review, and 422 studies for analyses. Sensitivity analyses that adjusted for sample size and study quality were conducted using standardized tools. The study protocol is registered (PROSPERO CRD42018090857). RESULTS:Ageism led to significantly worse health outcomes in 95.5% of the studies and 74.0% of the 1,159 ageism-health associations examined. The studies reported ageism effects in all 45 countries, 11 health domains, and 25 years studied, with the prevalence of significant findings increasing over time (p < .0001). A greater prevalence of significant ageism-health findings was found in less-developed countries than more-developed countries (p = .0002). Older persons who were less educated were particularly likely to experience adverse health effects of ageism. Evidence of ageism was found across the age, sex, and race/ethnicity of the targeters (i.e., persons perpetrating ageism). CONCLUSION:The current analysis which included over 7 million participants is the most comprehensive review of health consequences of ageism to date. Considering that the analysis revealed that the detrimental impact of ageism on older persons' health has been occurring simultaneously at the structural and individual level in five continents, our systematic review demonstrates the pernicious reach of ageism

Increasing negativity of age stereotypes across 200 years: evidence from a database of 400 million words.

Scholars argue about whether age stereotypes (beliefs about old people) are becoming more negative or positive over time. No previous study has systematically tested the trend of age stereotypes over more than 20 years, due to lack of suitable data. Our aim was to fill this gap by investigating whether age stereotypes have changed over the last two centuries and, if so, what may be associated with this change. We hypothesized that age stereotypes have increased in negativity due, in part, to the increasing medicalization of aging. This study applied computational linguistics to the recently compiled Corpus of Historical American English (COHA), a database of 400 million words that includes a range of printed sources from 1810 to 2009. After generating a comprehensive list of synonyms for the term elderly for these years from two historical thesauri, we identified 100 collocates (words that co-occurred most frequently with these synonyms) for each of the 20 decades. Inclusion criteria for the collocates were: (1) appeared within four words of the elderly synonym, (2) referred to an old person, and (3) had a stronger association with the elderly synonym than other words appearing in the database for that decade. This yielded 13,100 collocates that were rated for negativity and medicalization. We found that age stereotypes have become more negative in a linear way over 200 years. In 1880, age stereotypes switched from being positive to being negative. In addition, support was found for two potential explanations. Medicalization of aging and the growing proportion of the population over the age of 65 were both significantly associated with the increase in negative age stereotypes. The upward trajectory of age-stereotype negativity makes a case for remedial action on a societal level