Part I | The origin of aging - Ageless
A personal summary of A. Steele's book "Ageless"
This first article is a summary of the first part of the Ageless book, entitled “An age-old problem”. It starts by an introduction to the fact that, unlike for most our history, we now live at a time when a large majority us will experience aging. The explanation of why we age from an evolutionary viewpoint in then provided.
The age of aging
Andrew Steele starts by providing a history of human lifespans and health-spans, from prehistoric times to nowadays. From the beginnings of human kind until the rise of modern medicine, hygiene and industrialisation (i.e the beginning of the 19h century), human lives lasted approximately 40 years. Back then, high child mortality rates and infectious diseases (mainly) kept the number of persons that could experience the effects of aging very low. Life expectancy in developed countries has since increased very steadily until today, following progress in medicine, lifestyle, diets, the drop of smoking, etc. The standard periods of a life now are :
Education
Work
Retirement.
In this scheme, the major cause of death has become age-related diseases (Alzheimer, cancer, heart diseases…) happening late in life. The subsequent unprecedented increase of the fraction of old people in our society is then discussed by A. Steele, particularly how it weights on people’s emotions, but also on the economy through pension provision, health and social care, and so on. To live in an age when so much human and economical trouble is attributed to one cause is humbling but also exciting. But we’ll discuss the ethical case for postponing aging in another post…
The origin of aging
Aging is then examined through the lens of the theory of evolution. In fact, the theory of evolution is backed up by so much empirical and theoretical evidence that, as famously phrased by Theodosius Dobzhansky:
“Nothing in Biology Makes Sense Except in the Light of Evolution”.
In line with this idea, two main questions are explored.
A. If evolution by natural selection optimizes the survival of individuals, why do living creatures age and die?
Two explanatory hypotheses have been put forward but later considered wrong:
The theory of increasing of entropy, stating that any close system can only have an increasing entropy in time, and thus end up loosing energy at some point. This can not be used to explain aging because the second law of thermodynamics can not be applied to living things, which are not closed systems! It is then theoretically possible that organisms stay healthy as long as some of the energy they absorb (through food, light…) is used for cells and organ maintenance.
The sacrifice of older individuals through group selection by A.R. Wallace, according to which old animals die to let the young access environmental resources. This theory, and in fact many others relying on group selection, are not widely accepted today because they appear unstable, vulnerable to the spread of "selfish" individuals that could emerge by chance and out-compete all others.
What is it then? The consensual idea is now that natural selection did not have the ability to keep older individuals fit because of extrinsic mortality (i.e the risk of dying because of an external danger). Given the high chances of being killed by something in the environment before arriving at an old age, natural selection could only optimise traits in favour of reproduction and health earlier in life, when a lot of individuals are competing to pass on their genes. This evolutionary neglect manifests through two mechanisms (that are not mutually exclusive):
The accumulation of mutations at old ages. If a genetic mutation only impacts health after the standard reproductive age and when fewer individuals are left because of dangerous environments, evolution had no power to select against it. (For example, Huntington's disease appears generally after 40.)
Antagonistic pleiotropy. Some genes have different effects on an organism depending on the life stage. In the context of aging it means that some genes will be selected in populations because they grant a reproductive advantage in young individuals, but those same genes will also be responsible for health deterioration later in life. Examples of antagonistically pleiotropic genes are at play in the "disposable soma theory". This expression reflects an evolutionary trade-off where the limited amount of energy absorbed from the environment can either be allocated to the maintenance of reproductive cells or to all other cells, called somatic cells. In a dangerous environment, evolution favoured genes directing energy toward reproductive fitness to ensure that individuals have many offspring as soon as possible before dying from external causes. But such an energy allocation is to the detriment of the parent's (disposable) body maintenance, thus having deleterious repercussions later in life.
These two theories, especially the first one, cast a shadow on aging biology for many years. They discouraged scientists from finding simple mutations or pathways linked to senescence, which appeared to be the result of multiple, independent, incoherent genetic drifts overseen by evolution. It remained to be proven that something else than the force of natural selection over millennia could shape longevity.
B. How can we explain the striking diversity in the lifespans of living creatures?
The attentive reader may already have guessed that the evolved lifespan of a creature is intimately linked to extrinsic mortality. For species living in safe environments, or whose characteristics combined to the environment (like size or intelligence) have granted more chances of survival, evolution favoured soma maintenance over quick reproduction (like large whales, or naked mole rats inhabiting safe undergrounds). In this case, evolution had enough grip to select against mutations with a negative impact on health in old individuals. In contrast, frail creatures in hostile places evolved efficient and early reproductive strategies, leaving the few remaining old individuals to break down with age (like mice or insects). Extrinsic mortality can be seen as regulating the trade-off between soma maintenance and reproduction.
Some species diverge from this paradigm (as always, exceptions in biology are numerous), and become negligibly senescent by other means. Some female fishes and tortoises see their fertility increase over time: they become bigger, safer, and can lay more eggs, which incentivised the maintenance of soma cells. Other creatures with regenerative capabilities like hydras do not have distinct somatic and sexual cells, which offers them extremely long lives and lets them escape the disposable soma dilemma.
Longevity in trees could also be linked to competition for space as some trees have to outlive their competitors to grant their offspring a place to germinate in arid territories.
In conclusion, longevity is thought to be modulated by
extrinsic mortality, and
the relative importance of reproduction at different ages,
which created a very broad spectrum of lifespans in nature. As A. Steele enthusiastically puts it:
Negligible senescence not only doesn't break the laws of physics - it doesn't break any laws of biology either.
Which is great news for anyone trying to cure aging!
The next post will sum-up known mechanisms involved in aging, and possible solutions to treat them as they appear in Ageless.
Related content:
Theodosius Dobzhansky’s article for the quote:
“Nothing in Biology Makes Sense Except in the Light of Evolution”
Recent articles about the decline of natural selection strength with age like this one show that the specifics and causative chain of events of this current explanatory hypothesis are still being worked out.
A. Steele’s book website and code for Ageless. He generated helpful visuals, like for instance the exponential chance of death as a function of age:
Death rate as a function of age for several developed countries. The plot is from Andrew Steele, based on data from the Human Motrality Database.
