Can microbial infections make you age faster? Last week, Alzheimer’s experts cited several lines of indirect evidence linking infections to dementia. There have been other reports, going back decades, suggesting that infections early in life are associated with shorter life expectancy far down the road. “Makes sense” was the comment quoted from medical scientists.
It “makes sense” in that most biologists still want to believe that the body is doing its best to live as long as possible, and that every challenge to the body ought to have a negative impact on longevity, as the body’s resources are diverted from the task of constant repairing and rebuilding. [Science Times article based on article in Science Translational Medicine]
But we know, or should know by now, that the biology of aging doesn’t “make sense” in this way. The word hormesis describes the startlingly unexpected phenomenon that, if the body survives a challenge, it tends to age more slowly and live longer.
Science is driven by hunches and intuitions as much as by observations and theories. And in the area of aging medicine, scientific intuitions are stuck in a discredited paradigm that is holding us back. We look ever more creatively, ever less credibly, for something that is forcing the body to tolerate a deterioration that we know is not a necessary byproduct of life. We have been slow to face up to the fact that the body is choosing to be old, because we believe that “nature is beneficent” or because we can’t stomach the idea that our bodies are mutineers and we its victims, or because at some subconscious level we have been influenced by a narrow version of Darwin’s evolution.
The germ theory of AD is “logical” within this discredited paradigm. If the body is asked to fight off infection, then maybe it’s “distracted” from doing the repair work. To its credit, the new Harvard Med paper is a step above this delusion, however. Maybe the body is countering infection by mounting an inflammatory response that would be a healthy, useful adaptation in other tissues, under different circumstances; but in the brain it happens to wreak havoc, because there is no local mechanism for cleaning up the detritus from this war. We need only hypothesize that the body has evolved a general response that happens to be counter-productive in this one instance, and that evolution hasn’t had time as yet to create an exception to the rules about what threats to respond to, where, and how to respond.
The weak link, of course, is that we must assume that evolution made a mistake. A response that is generally appropriate is applied in a circumstance where it’s not just inappropriate, it’s deadly.
(from the article in Science Translational Medicine)
- Researchers injected nasty bacteria into mouse brains. Plaques appeared quickly, similar to those associated with AD.
- When this experiment was repeated with mice that were immune-suppressed so as not to respond to the bacteria, the bacteria killed them quickly. (Clearly this was a worse result than AD.)
- In humans, infection with herpes is statistically associated with AD.
- The blood-brain barrier weakens with age. First area of leakage is the hippocampus, which is often where amyloid plaques are known to begin. (This is the “mistake”.)
This is new to me, and I would not have predicted that the association with infection is as strong as it seems to be. But we have known for a long time that inflammation is powerfully associated with AD, and that infection promotes inflammation. I would ask what the new data suggests that adds to those important and well-established insights.
If the new Harvard Med hypothesis holds up, it still doesn’t address the issue of why the body should allow its brain to be destroyed by an inflammatory response. We know that anti-inflammatories have a big deterrent effect on AD. People who take NSAIDs have lower rates of dementia. In regions where the anti-inflammatory spice turmeric is a daily staple, the rate of dementia is a fraction of what it is in the West. So if the inflammation and amyloid accumulation turn out to be a response to real infections, not just auto-immunity, then the body is still making a big mistake in mounting this defense in a situation that actually does a lot more harm than good. One might be excused for thinking that evolution can’t afford such mistakes.
Background: Claims that early infections are associated with late mortality
My father’s Aunt Tillie (yes, that’s her real name) was a sickly child, and my great grandmother was in constant fear she was going to die. But she did manage to emerge from girlhood, and then went on to outlive three husbands. It took a nursing home to kill her at the age of 92. I have heard other stories that give the impression this is typical: children who survive severe illness in infancy tend to exceptionally long lives. Could it be that this is a myth, and the opposite is statistically true?
I have a new acquaintance with a venerable guru of aging science, Caleb Finch. Finch’s second encyclopedia contains an account of researches by David Barker in the 1980s that correlate conditions in early life with late-life mortality. One of the claims is that an infant’s lung infections can lead to heart disease as well as stomach conditions and bronchitis late in life. If true, this would be the opposite of hormesis (my expectation). Finch cites supportive theory that the body’s supply of naive T cells is finite and not easily renewed, and that depletion of this reservoir might begin early in life.
I find Barker’s data in themselves inconclusive, because they are based on neighborhoods in England. It is too easy for me to imagine that those neighborhoods that are poor and disadvantaged have both sicker children and higher mortality among elders, with no individual causal relation between the two. The most economical explanation is the economic one.
Together with Eileen Crimmins, Finch wrote a series of papers about a decade ago [ref] purporting to build a case for the germ theory of aging. They look at cohort data from 19th and 20th century Europe, when mortality was in steady decline. Technology alone might be expected to produce concurrent decreases in old-age mortality and childhood mortality. But in fact the decrease in old-age mortality was delayed about 60 years behind the drop in childhood mortality, suggesting that it was the same cohort—the same individuals—who were benefiting. They take this as evidence that the benefit accrued just once, in childhood, and was remembered by the body later in old age. The lower level of inflammation persisted over a lifetime. Steadily increasing height during this period is taken as another indication that the lower burden of infections was producing generally improved health.
Maybe. I’ve been unable to find more direct evidence that would bear on the question whether infections early in life have a positive or a negative effect on longevity. In this 1989 study, rats raised germ-free lived 8% longer than conventional-clean, except if they were calorically restricted, in which case they lived 2% shorter. This 1971 study includes a comparison of 9 strains of mice raised in sterile vs conventional lab cages, and the differences appear to be as often positive as negative.
More recently, there has been appreciation of the complex interplay between bacteria and the immune system. It’s the auto-immune response—when the body turns against itself—that is connected to the ravages of age. But the relationship between bacteria and auto-immunity is not straightforward. Some bacteria at some times of life are essential for training the immune response to distinguish between self and “other”, while other bacteria at other times of life contribute to the corruption of the immune response. This new article from an MIT researcher summarizes how much we don’t know. The article features a new demonstration of the way Lactobacillus reuteri, a beneficial gut bacteria and common probiotic ingredient, promotes growth and health of the thymus gland, through the anti-aging hormone FOXN1.
The Bottom Line
The article on a bold new hypothesis ends by recommending a familiar strategem: target drugs to interfere with pro-inflammatory pathways. I couldn’t agree more.
At the end of the day, the stronger evidence is for hormesis, in other words, that (modest) hardships tend to lengthen life span. Even without other, more direct evidence, the phenomena of hormesis alone would be sufficient to tell us that aging is a choice that the body makes, in other words, an evolved program. But not all hardships are created equal, and the balance of evidence for infectious disease is that infections are more likely to shorten life span (long after the symptoms of the infection are absent) than to lengthen it.