Diabetes reduces semen quality and increasingly occurs during reproductive years. Whether diabetes medications have glucose-independent effects on the male reproductive system is uncertain. This st... Visual Preconception Antidiabetic Drugs in Men and Birth Defects in Offspring. Diabetes reduces semen quality and increasingly occurs during reproductive years. Whether diabetes medication... Background: Diabetes reduces semen quality and increasingly occurs during reproductive years. Diabetes medications, such as metformin, have glucose-independent effects on the male reproductive syst...

The evolution of senescence is often explained by arguing that, in nature, few individuals survive to be old and hence it is evolutionarily unimportant what happens to organisms when they are old. A corollary to this idea is that extrinsically imposed mortality, because it reduces the chance of surviving to be old, favors the evolution of senescence. We show that these ideas, although widespread, are incorrect. Selection leading to senescence does not depend directly on survival to old age, but on the shape of the stable age distribution, and we discuss the implications of this important distinction. We show that the selection gradient on mortality declines with age even in the hypothetical case of zero mortality, when survivorship does not decline. Changing the survivorship function by imposing age independent mortality has no affect on the selection gradients. A similar result exists for optimization models: age independent mortality does not change the optimal result. We propose an alternative, brief explanation for the decline of selection gradients, and hence the evolution of senescence.

Reducing lifespan inequality is increasingly recognized as a health policy objective. Whereas lifespan inequality declined with rising longevity in most developed countries, Danish life expectancy stagnated between 1975 and 1995 for females and progressed slowly for males. It is unknown how Danish lifespan inequality changed, which causes of death drove these developments, and where the opportunities for further improvements lie now. We present an analytical strategy based on cause-by-age decompositions to simultaneously analyze changes in Danish life expectancy and lifespan inequality from 1960 to 2014, as well as current Swedish-Danish differences. Stagnation in Danish life expectancy coincided with a shorter period of stagnation in lifespan inequality (1975–1990). The stagnation in life expectancy was mainly driven by increases in cancer and non-infectious respiratory mortality at higher ages (−.63 years) offsetting a reduction in cardiovascular and infant mortality (+ 1.52 years). Lifespan inequality stagnated because most causes of death did not show compression over the time period. Both these observations were consistent with higher smoking-related mortality in Danes born in 1919–1939. After 1995, life expectancy and lifespan equality increased in lockstep, but still lag behind Sweden, mainly due to infant mortality and cancer. Since 1960, Danish improvements in life expectancy and lifespan equality were halted by smoking-related mortality in those born 1919–1939, while also reductions in old-age cardiovascular mortality held back lifespan equality. The comparison with Sweden suggests that Denmark can reduce inequality in lifespans and increase life expectancy through a consistent policy target: reducing cancer and infant mortality.

Background: Of all lifestyle behaviours, smoking caused the most deaths in the last century. Because of the time lag between the act of smoking and dying from smoking, and because males generally take up smoking before females do, male and female smoking epidemiology often follows a typical double wave pattern dubbed the ‘smoking epidemic’. How are male and female deaths from this epidemic differentially progressing in high-income regions on a cohort-by-age basis? How have they affected male-female survival differences? Methods: We used data for the period 1950–2015 from the WHO Mortality Database and the Human Mortality Database on three geographic regions that have progressed most into the smoking epidemic: high-income North America, high-income Europe and high-income Oceania. We examined changes in smoking-attributable mortality fractions as estimated by the Preston-Glei-Wilmoth method by age (ages 50–85) across birth cohorts 1870–1965. We used these to trace sex differences with and without smoking-attributable mortality in period life expectancy between ages 50 and 85. Results: In all three high-income regions, smoking explained up to 50% of sex differences in period life expectancy between ages 50 and 85 over the study period. These sex differences have declined since at least 1980, driven by smoking-attributable mortality, which tended to decline in males and increase in females overall. Thus, there was a convergence between sexes across recent cohorts. While smoking-attributable mortality was still increasing for older female cohorts, it was declining for females in the more recent cohorts in the US and Europe, as well as for males in all three regions. Conclusions: The smoking epidemic contributed substantially to the male-female survival gap and to the recent narrowing of that gap in high-income North America, high-income Europe and high-income Oceania. The precipitous decline in smoking-attributable mortality in recent cohorts bodes somewhat hopeful. Yet, smoking-attributable mortality remains high, and therefore cause for concern.

The classical evolutionary theories of aging suggest that aging evolves due to insufficient selective pressure against it. In these theories, declining selection pressure with age leads to aging through genes or resource allocations, implying that aging could potentially be stalled were genes, resource allocation, or selection pressure somewhat different. While these classical evolutionary theories are undeniably part of a description of the evolution of aging, they do not explain the diversity of aging patterns, and they do not constitute the only possible evolutionary explanation. Without denying selection pressure a role in the evolution of aging, we argue that the origin and diversity of aging should also be sought in the nature and evolution of organisms that are, from their very physiological make up, unmaintainable. Drawing on advances in developmental biology, genetics, biochemistry, and complex systems theory since the classical theories emerged, we propose a fresh evolutionary-mechanistic theory of aging, the Danaid theory. We argue that, in complex forms of life like humans, various restrictions on maintenance and repair may be inherent, and we show how such restrictions are laid out during development. We further argue that there is systematic variation in these constraints across taxa, and that this is a crucial factor determining variation in aging and lifespan across the tree of life. Accordingly, the core challenge for the field going forward is to map and understand the mosaic of constraints, trade-offs, chance events, and selective pressures that shape aging in diverse ways across diverse taxa.

There is significant recent interest in Peto's paradox and the related problem of the evolution of large, long-lived organisms in terms of cancer robustness. Peto's paradox refers to the expectation that large, long-lived organisms have a higher lifetime cancer risk, which is not the case: a paradox. This paradox, however, is circular: large, long-lived organisms are large and long-lived because they are cancer robust. Lifetime risk, meanwhile, depends on the age distributions of both cancer and competing risks: if cancer strikes before competing risks, then lifetime risk is high; if not, not. Because no set of competing risks is generally prevalent, it is instructive to temporarily dispose of competing risks and investigate the pure age dynamics of cancer under the multistage model of carcinogenesis. In addition to augmenting earlier results, I show that in terms of cancer-free lifespan large organisms reap greater benefits from an increase in cellular cancer robustness than smaller organisms. Conversely, a higher cellular cancer robustness renders cancer-free lifespan more resilient to an increase in size. This interaction may be an important driver of the evolution of large, cancer-robust organisms.