Ageing is by no means a unitary process. Although our understanding of the biology of ageing is still very young, we have already identified dozens of mechanisms which generate the pattern of symptoms we refer to as ageing, and these myriad symptoms are markedly distinct from one another in terms of their function and their evolutionary origins.
Allow me to take two processes as examples: deleterious genes and oxidative stress.
There are, so far as we know, no genes which function to age our bodies, but our genome hosts an array of genes that can become harmful as we grow older (Kirkwood 2002). We are born with all of the harmful genes we will ever possess, give or take a small number of mutations which can occur through radiation or mistakes in replication. The reason that these genes can become harmful late in life, but not early on, is that genes are not all expressed all of the time, in all tissues. That is, some genes are not active in creating proteins unless they are in particular parts of the body, in particular stages of development.
Human beings get much sicker as they get old. Instead of a gradual winding down of activity, we suffer an ever-increasing range of maladies—cancers, infectious, environmental and heritable diseases, and these ailments constitute much of what we consider to be ‘old age’.
Some of the increase in disease is due to a depletion of the immune system which is caused by ‘immunosenescence’—a process through which the immune system grows weaker with age, causing the body to be less capable of repelling disease. In fact, as we age beyond 80, our risk of dying increases primarily due to an increasing risk of bacterial or viral infections (Pawelec 2006). Many of our genes seem to age us in this way, by doing less to defend us against illness or disability as we get older.
It is now known that there are genes which create a predisposition to a number of cancers, such as breast cancer. Many of these genes are ‘silenced’ until late in life, when they begin to function in a harmful way (Leslie 2006). And different versions of the same gene become active at different ages; for example, the apolipoprotein-E (APOE) gene has a common variant that changes the average age of onset of Alzheimer’s disease from 84 to 68 years of age (Corder et al. 1993).
As well as genes that allow the emergence of acute diseases like infections, cancers, and Alzheimer’s disease, we have genes that activate to produce chronic, low-level effects that are not categorised as diseases. For example, our bodies have genes for the expression of ‘pro-inflammatory’ cytokines, which produce the inflammatory response that is part of the immune system. As we age, these genes become dysregulated, causing the body to become chronically inflamed, and this inflammation is thought to be a major process behind a number of important age-related problems, like arthritis, arthero-sclerosis, dementia, osteoporosis, and heart disease (Capri 2006).
Some of our late-onset genes reflect a kind of evolved trade-off between different survival-affecting processes. For example, certain genetic processes cause elderly people to undergo a decrease in insulin-like growth factor 1, or IGF-1; this decrease leads them to have decreased muscle mass and bone density, but also protects against cancer by inhibiting the growth of tumours (Capri 2006). Proponents of the argument from evolution would likely wish to argue that this protective factor is an example of evolution’s ‘blind logic’. I will return to this point below.
It has been thought for a long time that the chemical oxidation of cells and cell nuclei is one of the major forms of age-related tissue damage. In 1954, the ‘free radical theory of ageing’ advanced the idea that all of the deleterious effects of ageing were caused by these oxidative reactions (Harman 2006). ‘Free radicals’—reactive molecules containing oxygen, such as hydrogen peroxide—react with molecules in the cells to oxidise them, and this damages the cells. Antioxidant enzymes in the liver and elsewhere in the body serve to safely remove free radicals from the body but the purification process is not perfect, and the free radicals are able to damage the organs before they are completely expelled (Holliday 1997).
According to Harman’s mitochondrial version of this theory, free radicals enter the body not only from the external environment but also as an essential byproduct of respiration, the process in which our mitochondria produce energy from food and oxygen. These free radicals oxidise both the cells and the mitochondria inside the cells. And as the mitochondria become damaged, they get worse at repairing the cellular damage, and so ‘oxidative stress’ accumulates in the tissues, until finally the cell falls apart. According to Harman, this accumulation of damage is the main process which causes the symptoms of ageing (Harman 2006). This last claim remains controversial, and indeed there is no firm consensus that any of the damage is caused by respiration, but there is now a strong consensus that oxidative stress is one of the key processes in human ageing (Lapointe 2010).
There is a range of evidence showing how oxidative stress contributes to the symptoms of old age. For example, the neurons of Alzheimer’s disease patients show oxidative stress (Ghanbari et al. 2004), and it has also been shown that high levels of oxidation are present in the brains of Parkinson’s syndrome patients (Beal 1996) and in the hearts of those with heart failure (Romero-Alvira and Roche 1996). Oxidative stress has also been associated with the formation of cancers, as tumours can form when the DNA in cell nuclei is damaged (Bartsch 2006; Federico et al. 2007).
However, oxidative stress also seems to act against cancer formation in one way. Aged, oxidised cells form a barrier in the body which stops fast-replicating tissues such as cancers from spreading (Lynch 2004). In this way, senescence prevents cancer—another mechanism by which it could be claimed that evolution has selected for us the best balance of traits to promote longevity.
How did These Processes Evolve?
It should be apparent by now that oxidative stress and deleterious genes cannot have evolved in the same way. Our protozoan ancestors did not have an APOE gene or a gene for breast cancer; these genes must have been introduced during the process of evolution. On the other hand, free radicals have been oxidising cells since the very beginning of our evolution, since they are ubiquitous in our environment. Hence there must be (at least) two explanations for emergence of both of these groups of processes.
It may seem puzzling that evolution has introduced genes which, by ageing us, cause us to become weaker and to eventually perish. Peter Medawar, in his 1951 inaugural lecture at University College, argued for a simple solution to the puzzle: that strongest force of natural selection affects those genes which become active prior to an individual’s death. Since we humans died very young for the bulk of our evolutionary history, late-acting deleterious genes would not have impeded an individual’s chance of surviving and reproducing, and so these genes were not selected against, and they gradually accumulated in the genome over time. Indeed, as George Williams later pointed out, some of these genes may have been actively promoted if they were beneficial in early life before becoming harmful in old age (Williams 1957). But as human beings became more organised and began to live longer, these genes began to produce harmful effects on the longest-lived individuals. This goes some way to explaining why we have so many genes which become harmful in the later stages of life.Footnote 3
This explanation is not quite sufficient, however, to explain why we experience ageing due to oxidative stress. Our cells do not oxidise because harmful genes accrued in our genome; we oxidise because we are constantly encountering free radicals, and so we still need to explain why we failed to evolve defences against oxidation, as some animals did. The longest-lived non-colonial animal, the ocean quahog Arctica islandica, lives for at least 400 years, and it appears to have evolved a much greater resistance against oxidative stress than human beings in the form of natural antioxidant chemicals (Abele et al. 2008; Ungvari et al. 2011). As well as these endogenous antioxidants, clams have evolved to have a very low metabolic rate and a correspondingly low rate of activity and growth, meaning that fewer free radicals are produced by the mitochondria, reducing the endogenous source of oxidative ageing.
Nearly every time one gene is selected at the expense of another, it will be a case of a tradeoff: something good being exchanged for something better. As Williams pointed out in his seminal paper, very few animals in nature survive long enough to reach old age. In an environment that includes predation and infectious disease, natural selection will therefore select traits that take effect earlier in life rather than later, and this will frequently mean that traits that are beneficial in old age are sacrificed (Williams 1957). Kirkwood takes this line of reasoning much further suggesting that natural selection very frequently makes such tradeoffs between longevity, fecundity, and capacities for active behaviours like food-seeking or self-defence (Kirkwood 2002). A. islandica, for example, could afford to invest all its evolutionary chips in cell maintenance and repair because it reproduces sparingly and moves very little.
The reason we age, then, is partly because we have failed to evolve sufficient defences against our environment causing our bodies to physically break down as time passes. It is partly because our evolution has preferred to produce a metabolic rate which is high enough to allow an active lifestyle but which thereby produces more endogenous free radicals. And it is partly because evolution has not, and will not, rid us of our late-acting deleterious mutations. And these failures of evolution are predictable outcomes of the essential nature of the selective process. These ideas are now supported by a consensus of scientists. In a position paper co-signed by 52 biologists of human ageing, Olshansky claims that ‘aging is a product of evolutionary neglect, not evolutionary intent’ (Olshansky et al. 2002).
These explanations, on their face, pose a fairly serious threat to the argument from evolution, at least as it is applied to the process of ageing. Ageing is not the result of an optimising process, it is merely a byproduct of an optimising process. Even if evolution is a ‘blind watchmaker’, to use Richard Dawkins’ metaphor, ageing does not seem to be part of the watch. Caplan suggests that this is fatal for the argument from evolution, since—he says—the arguments of philosophers like Fukuyama and Parens depend on the idea that evolved traits must necessarily ‘advance the evolutionary success of a species or population’ (Caplan 2005).Footnote 4
I think we need to be a little more careful than this. In the first place, virtually no traits exist in order to advance the success of the population as a whole, because the great majority of selective forces operate at the level of the individual (Williams 1972; Maynard Smith 1964). So the most reasonable version of the argument from evolution would depend only on the idea that evolved traits must advance the survival and reproductive successes of individuals.
And we do not yet have cause to reject the idea that ageing has advanced the evolutionary success of human individuals. Proponents of this view might object that when we decide to neglect some good, it is usually in order that we can direct our attention elsewhere. If the traits of senescence accrued in the genome through a process of evolutionary neglect, that may mean that some other beneficial trait was produced at the expense of long youth; and perhaps we cannot throw out the chaff (ageing) without losing the wheat (beneficial adaptations). For example, it could be that allowing cellular oxidation is the only tradeoff which would allow high rates of activity along with a relatively low susceptibility to cancer.
If human senescence is the price we have paid for our adaptive traits, like activity and cognitive capability, then perhaps there is a ‘ruthless adaptive logic’ to ageing after all—perhaps age has evolved as the necessary byproduct of an optimising process. And perhaps proponents of the argument from evolution might also point to the direct benefits of ageing: the cancer-protecting upsides of our most deleterious genes and of the process of cellular oxidation. These suggestions should seem implausible, but they are not certain to be false. If we are to completely reject the argument from evolution, we need to say a little more than Caplan does.