Genes and the ageing muscle: a review on genetic association studies

Western populations are living longer. Ageing decline in muscle mass and strength (i.e. sarcopenia) is becoming a growing public health problem, as it contributes to the decreased capacity for independent living. It is thus important to determine those genetic factors that interact with ageing and thus modulate functional capacity and skeletal muscle phenotypes in older people. It would be also clinically relevant to identify 'unfavourable' genotypes associated with accelerated sarcopenia. In this review, we summarized published information on the potential associations between some genetic polymorphisms and muscle phenotypes in older people. A special emphasis was placed on those candidate polymorphisms that have been more extensively studied, i.e. angiotensin-converting enzyme (ACE) gene I/D, α-actinin-3 (ACTN3) R577X, and myostatin (MSTN) K153R, among others. Although previous heritability studies have indicated that there is an important genetic contribution to individual variability in muscle phenotypes among old people, published data on specific gene variants are controversial. The ACTN3 R577X polymorphism could influence muscle function in old women, yet there is controversy with regards to which allele (R or X) might play a 'favourable' role. Though more research is needed, up-to-date MSTN genotype is possibly the strongest candidate to explain variance among muscle phenotypes in the elderly. Future studies should take into account the association between muscle phenotypes in this population and complex gene-gene and gene-environment interactions.

No or only population-specific effect of PON1 on human longevity: A comprehensive meta-analysis

Paraoxonase 1 (PON1) has been suggested as a plausible candidate gene for human longevity due to its modulation of cardiovascular disease risk, by preventing oxidation of atherogenic low-density lipoprotein. The role of the PON1 192 Q/R polymorphism has been analyzed for association with survival at old age in several populations, albeit with controversial results. To reconcile the conflicting evidence, we performed a large association study with two samples of 2357 Germans and 1025 French, respectively. We combined our results with those from seven previous studies in the largest and most comprehensive meta-analysis on PON1 192 Q/R and longevity to-date, to include a total of 9580 individuals. No significant association of PON1 192 Q/R with longevity was observed, for either R allele or carriership. This finding relied on very large sample sizes, is supported by different analysis methods and is therefore considered very robust. Moreover, we have investigated a potential interaction of PON1 192 Q/R with APOE epsilon4 using data from four populations. Whereas a significant result was found in the German sample, this could not be confirmed in the other examined groups. Our large-scale meta-analysis provided no evidence that the PON1 192 Q/R polymorphism is associated with longevity, but this does not exclude the possibility of population-specific effects due to the influence of, and interaction between, different genetic and/or environmental factors (e.g. diet).

A Review of Demographic Ageing in the UK: Opportunities for Rural Research

Demographic ageing is a global phenomenon. UK policy and research have, until recently, focused on national trends and implications and largely viewed ageing as a 'pensions and care' problem. While other and more positive aspects are beginning to be acknowledged, regional, local, and rural impacts remain underinvestigated. This paper, by reviewing the literature from several disciplines and countries, introduces a series of research questions that could usefully inform future geographical inquiry. It argues that the nature, experiences, and consequences of demographic ageing will vary across space, stage in the life course and numerous aspects of our everyday lives. Our current knowledge and understanding are but the tip of the iceberg in terms of the research opportunities that lie ahead.

British population and society in 2025:Some conjectures

The paper examines three aspects of demographic change and conjectures about their wider impact on British society. Two features of fertility behaviour are highlighted. The first deals with ethnic variations and the likely continuation of high fertility rates amongst women of South Asian origin. The second involves the continued bifurcation between career women and those for whom motherhood remains a central life project. International migration is also assessed and the contradictions within the 'Fortress Britain' strategy exposed. Britain will continue to receive migrants from overseas and British society will become increasingly multi-ethnic. The paper also examines the tensions between an increasingly ageing population and the development of increased ethnic and cultural diversity. The paper concludes with some implications of these changes for the discipline of sociology itself.

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. In particular, the analysis of the mutations occurring in different OXPHOS complex showed a complex scenario with a different mutation burden in 90+ subjects with respect to controls. These findings suggested that mutations in subunits of the OXPHOS complex I had a beneficial effect on longevity, while the simultaneous presence of mutations in complex I and III (which also occurs in J subhaplogroups involved in LHON) and in complex I and V seemed to be detrimental, likely explaining previous contradictory results. On the whole, our study, which goes beyond haplogroup analysis, suggests that mitochondrial DNA variation does affect human longevity, but its effect is heavily influenced by the interaction between mutations concomitantly occurring on different mtDNA genes

Physical Stature Decline and the Health Status of the Elderly Population in England

Few research papers in economics have examined the extent, causes or consequences of physical stature decline in aging populations. Using repeated observations on objectively measured data from the English Longitudinal Study of Ageing (ELSA), we document that reduction in height is an important phenomenon among respondents aged 50 and over. On average, physical stature decline occurs at an annual rate of between 0.08% and 0.10% for males, and 0.12% and 0.14% for females—which approximately translates into a 2cm to 4cm reduction in height over the life course. Since height is commonly used as a measure of long-run health, our results demonstrate that failing to take age-related height loss into account substantially overstates the health advantage of younger birth cohorts relative to their older counterparts. We also show that there is an absence of consistent predictors of physical stature decline at the individual level. However, we demonstrate how deteriorating health and reductions in height occur simultaneously. We document that declines in muscle mass and bone density are likely to be the mechanism through which these effects are operating. If this physical stature decline is determined by deteriorating health in adulthood, the coefficient on measured height when used as an input in a typical empirical health production function will be affected by reverse causality. While our analysis details the inherent difficulties associated with measuring height in older populations, we do not find that significant bias arises in typical empirical health production functions from the use of height which has not been adjusted for physical stature decline. Therefore, our results validate the use of height among the population aged over 50.

Prevalence of potentially inappropriate prescribing and prescribing omissions in Irish adults: findings from the Irish LongituDinal Study on Ageing (TILDA)

Purpose: We sought to estimate the prevalence of potentially inappropriate prescriptions (PIP) and potential prescribing omissions (PPOs) using a subset of the STOPP/START criteria in a population based sample of Irish adults aged ≥65 years using data from The Irish LongituDinal Study on Ageing (TILDA).

Methods: A subset of 26 PIP indicators and 10 PPO indicators from the STOPP/START criteria were applied to the TILDA dataset. PIP/PPO prevalence according to individual STOPP/START criteria and the overall prevalence of PIP/PPO were estimated. The relationship between PIP and PPOs and polypharmacy, age, gender and multimorbidity was examined using logistic regression.

Results: The overall prevalence of PIP in the study population (n = 3,454) was 14.6 %. The most common examples of PIP identified were NSAID with moderate-severe hypertension (200 participants; 5.8 %) and aspirin with no history of coronary, cerebral, or peripheral vascular symptoms or occlusive event (112 participants; 3.2 %). The overall prevalence of PPOs was 30 % (n = 1,035). The most frequent PPO was antihypertensive therapy where systolic blood pressure consistently >160 mmHg (n = 341, 9.9 %), There was a significant association between PIP and PPO and polypharmacy when adjusting for age, sex and multimorbidity (adjusted OR 2.62, 95 % CI 2.05–3.33 for PIP and adjusted OR 1.46, 95 % CI 1.23–1.75 for prescribing omissions).

Conclusion: Our findings indicate prescribing omissions are twice as prevalent as PIP in the elderly using a subset of the STOPP/START criteria as an explicit process measure of potentially inappropriate prescribing and prescribing omissions. Polypharmacy was independently associated with both PPO and PIP. Application of such screening tools to prescribing decisions may reduce unnecessary medication, related adverse events, healthcare utilisation and cost.

Ageing through Austerity: critical perspectives from Ireland

The book’s main contribution is the bringing together of varied discourses concerning the social policy impact of ageing within the context of fiscal austerity. As the editors rightly state, the economic recession has sharpened the focus of governments on the implication of demographic ageing. It is vital therefore, that the social policy implications of societal ageing are studied and understood within a wider political economy of austerity. Of course the fiscal crisis of the 1970s and the ensuing first wave of neo-liberalism in the Anglo-Saxon countries [in the 1980s] gave us a foretaste of the various ways in which the public burden thesis has been applied with great force to the older population. This recession is different, certainly in Ireland, but a combination of neo-liberal ideology and neo-classical economics is enforcing severe budgetary constraint on a range of countries (within and outside of the Eurozone) in the name of funding deficits. Policy makers appear to be disinterested in both the origins of the 2008 financial crisis and the distributional consequences of their austerity policies. In the absence of official concern social science research has a key role to play.

Ageing and the immune system: focus on macrophages

A fully functioning immune system is essential in order to maintain good health. However, the immune system deteriorates with advancing age, and this contributes to increased susceptibility to infection, autoimmunity, and cancer in the older population. Progress has been made in identifying age-related defects in the adaptive immune system. In contrast, relatively little research has been carried out on the impact of ageing on the innate immune response. This area requires further research as the innate immune system plays a crucial role in protection against infection and represents a first line of defence. Macrophages are central effector cells of the innate immune system and have many diverse functions. As a result, age-related impairments in macrophage function are likely to have important consequences for the health of the older population. It has been reported that ageing in macrophages impacts on many processes including toll-like receptor signalling, polarisation, phagocytosis, and wound repair. A detailed understanding of the impact of ageing on macrophages is required in order to develop therapeutics that will boost immune responses in the older population.