The evolution of aging

Spawn til you die by Ray Troll

Spawn til you die by Ray Troll

Selection is powerful, but has limits in maintaining function, especially with advancing age. Moreover, tradeoffs involving selection are ubiquitous in biology, and can help explain the evolution of aging.

As an example, I am more likely to admit a 70 year old with chest pain than a 20 year old. Understanding age-related risk of death and age-related complications of procedures can be best understood as an outcome of evolution of life history traits.

We are going to cover evolutionary hypotheses of senescence during this week. These hypotheses include antagonistic pleiotropy, declining power of selection, and mutation accumulation.  This link does a nice job of explaining the concepts.

Antagonistic pleiotropy is the concept that a gene for survival or a gene that promotes
reproduction early can be selected for even if it kills you at a later
age. So selection favors juvenile survival at the expense of old age survival. This hypothesis recognizes that most traits have both costs and benefits, and are tradeoffs. The tradeoff in antagonistic pleiotropy is improved health in youth, but disease in old age.

Haldane and Medawar proposed the declining power of selection hypothesis of aging. This proposes that genes for maintenance and repair of the body are selected for more strongly at early ages (pre-reproduction) than after reproductive age. For this: imagine a hypothetical gene that prevents cancer at age 10 and another gene that prevents cancer at age 100. The gene that prevents cancer at age 100 will not have any effect most of the time because most people are dead by age 100 (this remains true even if you take senescence out of the equation – random accidents will claim many lives). The gene that affects 10 year olds is more likely to be expressed and have a benefit simply because most people are alive at age 10. Therefore the old-age gene will be invisible to natural selection, the gene that affects 10 year old will be subject to positive selection.

Medawar extended his idea to include mutation accumulation. This idea posits that the body accumulates deleterious mutations at late ages that, because of the declining power of selection, are not selected against, and thus accumulate. In wild populations, not enough organisms reach advanced age, so these mutations are invisible. If allowed to achieve advanced chronological age, these mutations exert damaging effects, reducing fitness and contributing to senescence.

The disposable soma hypothesis is another idea to explain aging. This hypothesis recognizes that the nonreproductive part of the body (the soma) exists only to support the reproductive part of the body. At any moment in time an adult can devote energy to the maintenance of the body or to reproduction. Put simply, after successful reproduction, the soma is “disposable”, and genes are passed on. This tradeoff is vividly illustrated in adult salmon, which appear to do all their aging at once, immediately after a single reproductive effort. In many animals, bearing offspring shortens lifespan. There is some evidence of this in humans too.

Writing Assignment

Menopause is a strange phenomenon, because it represents premature aging of the female reproductive organs, asynchronous with the rate of decline in function for the rest of the body. It is paradoxical because it would seem that natural selection would favor maximal reproduction throughout the lifespan for humans. Given the fitness benefits of continued reproduction, why does the female reproductive organ age faster than the rest of the body? Humans are nearly unique in having a menopause; apparently killer whales are another example (see below).

Some suggest that menopause evolved because grandmothers are more successful at passing on their genes by investing in grandchildren than in more babies of their own. Others argue that menopause is a consequence of modern medicine prolonging the lifespan of women past 60 when most pre-historic women would be dead. So in the past reproductive aging would have been in sync with aging of the rest of the body. In this view menopause reflects the early mortality in pre-history and is a gene-environment mismatch.

In 3/4 page, explain why women cease to reproduce in middle age? Do you agree with the Grandmother hypothesis?

Readings for next week:

1. Age-old-question Flatt T and Promislow EL. 2007. Science (318) 1255-1256.

2. Why do we age? Kirkwood Austad Nature 2000

3. Evolution of the human menopause Shanley DP and Kirkwood TB. 2001 Bioessays 23. 282-287.

4.  Menopause in killer whales

(Read also the Alcock and Schwartz 2011 and Stearns 2013 papers in the previous post.)

Welcome Evo Med Students

The 2014 UNM Evolutionary Medicine course meets for the first time today in Castetter Hall room 258. (The illustration above shows a timeline of first antibiotic use and date of first recorded antibiotic resistance – from Clatworthy et al. 2007 Nat Chem Biol 3, 541-8). In this class we will discuss antibiotic resistance and a wide variety of other evolutionary topics in medicine.

Readings for this week include:

1. Alcock and Schwartz 2011 A clinical perspective in Evolutionary Medicine: What we

wish we had learned in medical school. Evolution: Education and Outreach, 2011.

2. Stearns . Evolutionary Medicine: Its Scope, Interest, and Potential. Proceedings of the Royal Society B, 2013.

Here are the slides from the first lecture: Introduction to Evolutionary Medicine 2014


Microbial Manipulation in the New York Times – Updated.

“Maybe the microbiome is our puppet master”

So writes Carl Zimmer, reporting on a paper that Athena Aktipis and Carlo Maley and I wrote about microbial manipulation of human behavior. Zimmer’s article appears in the New York Times Science section.

Update! Alcock, Maley, and Aktipis was featured on the Evolution and Medicine Review.

Click on the link to read our Bioessays abstract:

Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms

Also: read this excellent recent review on the same topic by Mark Lyte (full text):

Microbial endocrinology: host-microbiota neuroendocrine interactions influencing brain and behavior.


10 ways evolution can improve medical care

Here are 10 common pitfalls in medical practice that could be avoided if doctors apply evolutionary principles to health and disease.

1) Interfering with adaptations (relevant to acute disease, development, and life history).

2) Triggering adaptive mechanisms in the wrong setting (mismatch).

3) Misunderstanding adaptive and non-adaptive sources of human genetic variation

4) Unwittingly acting as an agent of selection – creating antibiotic resistance

5) Agent of selection – selecting virulent strains by increasing disease transmission

6) Agent of selection – selecting resistant clones in cancer treatment

7) Agent of selection –  selecting insecticide resistance (e.g. prescribed insecticidal bed nets)

8) Agent of selection – selecting for altered microbial communities

9) Failure to recognize competing fitness interests as source of disease – genetic conflicts

10) Failure to recognize competing fitness interests – infection/parasite/microbiome involvement in chronic disease

As you can read, these items fall in three main categories – I. Misunderstanding of adaptation in human biology, II. Acting as an agent of selection, III. Failure to recognize how competition between genomes causes disease. We will cover these categories during the 2014 evolutionary medicine course. Examples to follow soon.

Currently, there is space for novel evolutionary approaches in medicine because physicians are not accustomed to think (or communicate) in terms of natural selection, adaptation, and evolutionary trade-offs. If the medical community is given concrete examples how evolution can improve health care, I expect that things will change rapidly. One of my goals is to provide those examples. Some day, perhaps, there will be no need for an “evolutionary” medicine because all medicine will be evolutionary.


Fever and the Acute Phase Response – Updated!

This is part two of a post on the evolution and adaptive value of fever and whether physicians should be treating it . Read Part 1 here first.

Sir William Osler wrote:

‘Humanity has but three great enemies:
fever, famine and war; of these by far the greatest,
by far the most terrible, is fever’


Over a century ago, when Osler spoke those words at an address to the American Medical Association, fever was deemed a grave threat to survival. Of course, Osler used fever as a shorthand for infection, and this was in the pre-antibiotic era. However,  fever continues to be a contentious area in critical care medicine.

Young and Saxena have a must-read recently published review in the journal Critical Care on fever and its treatment.

They write:

“Remarkably, at present we do not know what effect treating fever in critically ill patients with infections has on patient-centered outcomes.”


“arguments based on the evolutionary importance of the febrile response do not necessarily apply to critically ill patients who are, by definition, supported beyond the limits of normal physiological homeostasis. Humans are not adapted to critical illness.”

While it is true that humans are not adapted to current treatments of critical illness – being on a ventilator, receiving medications by central venous line, getting dialysis – humans certainly have been getting seriously ill from infections throughout human and pre-hominin evolution. It would follow that fever benefited many of our ancestors. So why is it so hard to figure out whether fever is a good or bad thing for our sickest patients in the hospital?

Along these lines an excellent point counter-point series was published in the journal Chest last year.

In the first, Drewry and Hotchkiss  argue for giving antipyretic (anti-fever) treatment for patients with sepsis (blood infection).

In a rebuttal, Moer and Doerschug write that we should not ignore the evidence that cooling febrile patients with sepsis can save lives; they also concede the following:

“Fever is an adaptive response and affords some host protection” and “Fever control in life threatening infection merits further high-quality study.”

I agree with those conclusions, if not the contention that we should be routinely cooling our patients. If fever is adaptive, which all these authors agree is true, then its benefits should be manifested most when there is a high risk of death. After all, mortality is the main driver of selection for host responses, like fever and the acute phase response generally.

So what is the evidence:

This forest plot, from Moer and Doerschug illustrates the benefit/harm from cooling therapies. No single study reaches significance either way, and the group analysis leaves room to question still whether these therapies help or hurt patients:

Forest Plot Antipyretic Treatment

One of the studies above was this randomized controlled trial by Schortgen and colleagues, suggesting a benefit from external cooling blankets in critically ill patients. They reported improved 14 day mortality, although no difference was seen in 90 day mortality.

Obviously this in an ongoing area of controversy and study. We will keep our eyes out for what should be a definitive trial of antipyretic therapy – the HEAT trial - a large randomized controlled trial of antipyretics currently being conducted by Young and colleagues.

Updated: Podcast link!

Update: Listen to Paul Young give an evolution-minded lecture on the function of fever and the HEAT trial

 (Skip to minute 3:48 for the beginning of the talk)

A visit with Michael Hochberg

I visited evolutionary biologist Michael Hochberg at the Santa Fe Institute today. After a tour of the SFI facilities which are inhabited by permanent and visiting fellows, students, and transients like myself, we talked about his recent research involving bacteriophage control of human bacterial pathogens.

Credit Wikimedia

Credit Wikimedia

Since antibiotic resistance is a huge and worsening problem, there is greater emphasis on discovering alternate strategies to destroy infection causing microbes.

Hochberg and colleagues studied the ability of bacteriophages to kill Pseudomonas aeruginosa, a common bug implicated in nosocomial, or hospital-acquired, infections.

In a novel strategy Hochberg and colleagues evolved the bacteriophage, passaging the virus through generations of infection on plates of Pseudomonas. In essence they were selecting for fit strains of bacteriophage that were efficient killers of Pseudomonas. After a few generations of evolution, the phages had deadly ability to obliterate the original strain of bacteria.

It is worth noting that the bacterium also evolves during this process, and the co-evolution of bacterium and phage can reveal interesting patterns in line with expectations of the Red Queen effect.

Read Hochberg’s full paper here

New and emerging diseases – Updated!

Arrival of Chikungunya Virus in the New World: Prospects for Spread and Impact on Public Health

Chikungunya sounds exotic, but in fact it is the name of a mosquito-borne viral syndrome that is increasingly found to the New World (closer to home for me and many readers of this blog). Originally from West Africa, Chikungunya has been common in that continent and Asia for many years. Only recently has it been isolated form patients in the Western hemisphere. For background, read this excellent piece by Weaver about the recent spread of Chikungunya. Outbreaks in several Caribbean countries have been ongoing, especially Haiti and the Dominican Republic. Patients who have been in the Caribbean have presented to emergency departments, including the one where I work.

Last month, the first documented case of transmission occurred in Florida. Just this week, a mosquito tested positive for Chikungunya in Houston, Texas. This evidence of endemic spread suggests that Chikungunya may be here to stay.

One development that has promoted the spread of this virus in Asia is that the virus has switched vectors, from Aedes egypti to Aedes aldopictus  tiger mosquitoes. Both of these mosquitoes exist in the Southern US.

Phylogenetic techniques have been used to track the spread of this virus. Evolutionary work has revealed interesting evolutionary patterns as the virus adapts to new vector and novel habitats.

Read more about the Houston Chikungunya virus positive mosquitoes here

New update: researchers have reported success with a vaccine against Chikungunya virus. Read the article in the New York Times.