Fight Aging!

Our species evolved to perpetuate itself in a very different environment from the one we find ourselves in now. We are clearly far better off as individuals: lives are a good deal less nasty, brutish, and short than was the case for our distant ancestors. Technological progress has conquered a sizable slice of the death and disease of childhood and early adult life, to a degree varying by the wealth of any given region of the world. The worst half of infectious disease is controlled, but chronic age-related diseases remain poorly managed, and the incidence of these diseases rises inexorably as people live longer due to continued incremental improvements in medicine - but also as people become sedentary and overweight, the evolved human response to technologies of transport and abundant calories.

We might ask to what degree this situation can be considered a mismatch between environment and evolved adaptation. Is widespread age-related disease a problem that emerges with technology and its consequences because that technology has arrived over a short time frame, and thus previously evolved characteristics and biochemical mechanisms are square pegs faced with a suddenly round hole? We might think of our need for exercise to maintain health and function, coupled to a civilization in which ever fewer people are running down game animals or otherwise engaged in earnest physical activity day in and day out.

Alternatively, is this a preexisting problem that is now exacerbated by natural selection ongoing in the short time frame of modern technology, favoring harmful adaptations? What does a sudden, continual, unending abundance of calories do to a species that previously evolved through hundreds of thousands of years of feast and famine? What genes and traits are quickly selected? How might epigenetic inheritance based on calorie intake run awry? These and other, similar questions do not have good answers at this time, though there is certainly enough research to enable speculation. As is the case for deep investigations in the detailed progression of human aging in the natural state, full answers might never arrive, as the present situation will be swept away by the advent of practical rejuvenation therapies and the ethical imperative to use them.

The dark side of our genes - healthy ageing in modern times

Over the last four centuries human ecology, life styles, and life histories have dramatically changed. The transition to modernity also altered the major causes of human death. Infectious diseases prevalent in childhood have given way to chronic diseases associated with ageing. Naturally - as all of us must die - if some causes of death decrease others must increase in proportion. However, the increasing differences between the circumstances our genes have adapted to and our new environment also plays an important role.

Ageing is, in part, caused by the combined effect of many genes that are beneficial when young, but have adverse effects at older ages. Genes can influence a variety of traits and can also express themselves differently as we age (pleiotropy). The term antagonistic pleiotropy describes genes that can carry both beneficial and detrimental effects. Somewhat counter-intuitively evolution by natural selection can lead to antagonistic pleiotropy spreading in populations: The benefits received when young can outweigh the evolutionary disadvantages in old age. Some variants of the gene BRCA1 are, for example, beneficial to fertility. However, women who carry one of such variants of BRCA1 will - more likely than not - develop breast cancer by the age of 90.

In contrast, the evolutionary impact of contemporary life on human health is difficult to establish: evolutionary change often requires many generations to leave an unambiguous trace in our genome. The review found "suggestive but not yet overwhelming" evidence that natural selection, the engine of evolution, is changing course in our modern times. Several studies in pre- and post-industrial populations point, for example, to a selection toward an extended fertility period in women.

"We have to be cautious here, though. Changes in human biology are driven by two non-exclusive processes. The environment directly impacts how our genes are expressed: Bad nutrition in childhood can cause, for example, stunted growth. But the environment also shapes natural selection. Natural selection can make some genes more - and others less - frequent in the population over time: Lactose-intolerance in adults, for example. It's tempting to point to natural selection when we observe a particular change. However, particularly when the changes occurred recently, it is more likely that gene expression has changed, rather than that the genes themselves have adapted to a new environment."

The transition to modernity and chronic disease: mismatch and natural selection

The Industrial Revolution and the accompanying ecological, epidemiological, and demographic transitions - a combination that we call the transition to modernity (TTM) - have had a profound impact on human populations. Fundamental ecological changes driven by modernization include permanent improvements in nutrition and food security, a dramatic decline in exposure to pathogens and a global increase in exposure to air and water pollutants. Biological changes include shifts in our physiology, development, immunobiology, microbiota and life history traits and the age structures of our populations.

In the process, mismatches between our evolved capacities and our rapidly changing environment have emerged, with many consequences for health and disease. Previously evolved genetic effects mediated by antagonistic pleiotropy may now account for a substantial proportion of the increasing burden of non-communicable diseases, which are currently responsible for over 63% of the world's deaths. Of these deaths, 80% occur in low-income and middle-income countries, and half are in men and women of working age. Although important progress has been made in the past decade in stemming the rising death toll from noncommunicable diseases, they remain a substantial threat both to health and to global economic development.

If evolution in prior environments favoured alleles that are harmful to fitness in current environments, then selection should eventually either modify their effects or remove them from contemporary populations. Indeed, growing evidence suggests that the rates and sizes of recent phenotypic responses to mismatch can substantially alter the direction and intensity of natural selection for genes that contribute to important traits, such as age and size at first birth, body mass index (BMI), and age at menopause.

In this review, we focus on the impact of the ecological, epidemiological, and demographic changes driven by the TTM on human biology. We aim to answer two questions: how compelling is the evidence that once advantageous gene variants now contribute to the growing burden of non-communicable disease, and how compelling is the evidence that natural selection has started to improve survival and reproduction in humans living in recently changed environments? Our aim is to make clear the degree to which the TTM has revealed the ecological and evolutionary origins of much of the increasing burden of non-communicable diseases by changing both age structures and the leading causes of death. By informing our basic understanding of disease causes, this knowledge can help to guide the search for novel therapies.