Today, I thought I'd point out a few varied publications from the epidemiology research community. They have nothing much in common beyond being interesting and of relevance to the broader understanding of how aging progresses at the present time. The first addresses a common theme in recent years, which is to provide arguments against the misconception that excess weight is in any way beneficial in older age; the second adds data to the debate over whether there is in fact a physical, genetic basis for the correlation observed between intelligence and life expectancy; the third might be taken as an essay-length complaint about the state of the data and methodologies used to assess the degree to which longevity is inherited.
Epidemiology has a long history: if you trace back a great deal of today's aging research far enough, you'll eventually arrive at a starting point consisting of observations of large numbers of humans. Only in more recent decades has it become the case that lines of medical research relevant to aging can spring forth from examining the biochemistry of a few individuals, or of other species. Prior to the development of the tools of modern biotechnology, researchers had to start with the search for patterns in the demographics of life, disease, and death. That approach to medicine still continues today, of course, but it is slowly becoming divorced from those parts of the field that will make the greatest difference to the future of health and longevity.
Epidemiology can tell us things about how aging progresses in the absence of effective means to treat it. It can help to identify the difference between better and worse lifestyle choices, or find bearers of common genetic variants that somewhat improve resistance to the consequences of age-related cell and tissue damage. But epidemiology has nothing to say about the future of rejuvenation therapies: as a field it looks backwards, not forwards. It is the construction of a description of things as they are and were, not as they will be. Treatments capable of repairing the damage that causes aging will change the whole of the picture, and tomorrow will look nothing like today.
For older groups, being overweight [body mass index (BMI): 25 to 30] is reportedly associated with a lower or similar risk of mortality than being normal weight (BMI: 18.5 to 25). However, this "risk paradox" is partly explained by smoking and disease-associated weight loss. This paradox may also arise from BMI failing to measure fat redistribution to a centralized position in later life. This study aimed to estimate associations between combined measurements of BMI and waist-to-hip ratio (WHR) with mortality and incident coronary artery disease (CAD). This study followed 130,473 UK Biobank participants aged 60-69 years (baseline 2006-2010) for 8.3 years (n = 2974 deaths). Current smokers and individuals with recent or disease-associated (e.g., from dementia, heart failure, or cancer) weight loss were excluded, yielding a "healthier agers" group.
Ignoring WHR, the risk of mortality for overweight subjects was similar to that for normal-weight subjects. However, among normal-weight subjects, mortality increased for those with a higher WHR (hazard ratio: 1.33) compared with a lower WHR. Being overweight with a higher WHR was associated with substantial excess mortality (hazard ratio: 1.41) and greatly increased CAD incidence compared with being normal weight with a lower WHR. Thus for healthier agers (i.e., nonsmokers without disease-associated weight loss), having central adiposity and a BMI corresponding to normal weight or overweight is associated with substantial excess mortality. The claimed BMI-defined overweight risk paradox may result in part from failing to account for central adiposity, rather than reflecting a protective physiologic effect of higher body-fat content in later life.
Findings from prospective cohort studies based on populations from Australia, Sweden, Denmark, the US, and the UK indicate that higher cognitive ability (intelligence) measured with standard tests in childhood or early adulthood is related to a lower risk of total mortality by mid to late adulthood. The association is evident in men and women; is incremental across the full range of ability scores; and does not seem to be confounded by socioeconomic status of origin or perinatal factors.
Several hypotheses have been proposed to explain associations between intelligence and later risk of mortality. The suggested causal mechanisms put forward, in which cognitive ability is the exposure and disease or death the outcome, include mediation by adverse or protective health behaviours in adulthood (such as smoking, physical activity), disease management and health literacy, and adult socioeconomic status (which could, for example, indicate occupational hazards). Recent evidence of a genetic contribution to the association between general cognitive ability and longevity, however, might support a system integrity theory that posits a "latent trait of optimal bodily functioning" proximally indicated by both cognitive test performance and disease biomarkers. None of these possibilities are mutually exclusive.
We investigated the magnitudes of the association between childhood intelligence and all major causes of death, using a whole year of birth population followed up to older age, therefore capturing sufficient numbers of cases for each outcome. All individuals born in Scotland in 1936 and registered at school in Scotland in 1947 were targeted for tracing and subsequent data linkage to death certificates. For most endpoints, higher childhood intelligence was associated with a lower risk of cause specific death. Risk of death related to lifetime respiratory disease was two thirds lower in the top performing 10th for childhood intelligence versus the bottom 10th. Furthermore for deaths from coronary heart disease, stroke, smoking related cancers, digestive diseases, and external causes, risk of mortality was halved for those in the highest versus lowest 10th of intelligence. The risk of dementia related mortality and deaths by suicide were reduced by at least a third in the highest performing quarter of intelligence test score versus the lowest quarter.
In the literature, the familial component of human longevity has been investigated using survival to extreme age and age at death as phenotypes of survival. The former actually refers to longevity whereas the latter refers to individual or population based lifespan. Both definitions are often used in the context of longevity research which is confusing and incorrect. Another complication is that most studies exclude infant and child mortality by applying a lower limit age threshold when considering the lifespan of a population or group of individuals. Unfortunately, there is no consensus on the age threshold for longevity studies. As a result of both the inconsistent use of terminology and different lower and upper limit age thresholds, the comparison of longevity studies is generally problematic. We will refer to longevity as survival into extreme old ages whereas lifespan refers to age at death related measures.
Progress in longevity research is also hampered by the fact that longevity is likely dependent on an interplay between combinations of multiple genes and environmental factors which makes it difficult to separate environmental from genetic influences. In fact, environmental influences likely moderate genetic effects on longevity. Several genealogical studies have attempted to estimate the heritability of lifespan and longevity. These studies can be divided into two categories based on the type of data they used; (1) twin data and (2) pedigree data. Unlike animal studies in a lab setting, the effects of the environment on longevity in human studies cannot be controlled. In twins at least the variation in early environment is minimized as compared to other family based studies. In all cases, heritability estimates and the effect of specific gene variants on lifespan and longevity depends on the populations studied and their past and present environmental conditions.
It can be concluded from study results that the heritability of lifespan is between 0.01 and 0.27 in the population at large. The large variation in the heritability estimates indicates a prominent role for differential environmental influences on the estimates. Studies showing that siblings of centenarians and longevous sib-pairs have a high probability to also become a centenarian or longevous, respectively, and studies, which show that longevous parents have a high probability to bear longevous offspring, provide indications that the heritability of longevity may be higher than that of lifespan.
However, the heritability of longevity has only been investigated once in a twin study design, though of limited sample size. In addition, the heritability of longevity has been investigated more often in pedigree studies but the studies raise several questions about their design, sample size, and generalizability. Establishing the heritability of longevity is necessary for case definitions in genetic studies focused on gene mapping. Hence, researchers' attention should shift from lifespan to longevity and the heritability of longevity should be estimated in an appropriate design with a sufficiently large sample.