So far I’ve found that this gene: https://en.wikipedia.org/wiki/MCM6
controls production of lactase after infancy. But there are obviously lots of other stomach enzymes – do any of those also decrease after we age? One would expect that either enzyme production would remain constant or that _all_ enzyme production would decrease, yet that would have catastrophic effects, so it seems like lactase is the only enzyme whose presence decreases after age, which begs the question as to why.
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I wrote a paper about this in college. It is the genetic norm for adult humans to stop producing lactase as they age. This is normal due to the change in diet as we grow we no longer rely on lactose for our major source of food.
It is only in recent human history after the domestication of cattle did our bodies begin to adapt and continue to produce lactase into our adulthood
Animals don’t typically consume milk (the source of lactose) after they are weaned. So there is an energetic disadvantage in continuing to produce lactase post-weaning.
Humans are weird in that some populations consume the milk of other animals.
Production of specific enzymes can increase/decrease with demand. Eg your liver makes more or less of the enzyme that breaks down alcohol depending on how much you regularly consume. The body avoids wasting energy making things if they’re not being used.
Actually the interesting bit is not that lactase production is reduced in some people, but that it is retained in others! Lactose tolerance is the retention of a juvenile trait (ability to digest milk, important for baby mammals who evolved to drink it) into adulthood.
In general this is called neoteny, if you are interested in other examples. The classic example is axolotls essentially being salamander juveniles forever.
https://en.m.wikipedia.org/wiki/Neoteny
>One would expect that either enzyme production would remain constant or that all enzyme production would decrease,
Would one? Wouldn’t one expect digestive enzyme complement to reflect diet (re weaning)?
>so it seems like lactase is the only enzyme whose presence decreases after age, which begs the question as to why.
“Why?” is always a tricky question when it comes to natural selection. A better question may be “Is there any benefit?”.
Lactase should not be considered in isolation though. It should be considered together with lactose – the very special type of sugar, that mammals produce specifically for milk, despite not being able to digest it without also producing lactase.
So a better question is “what is he benefit of having a special sugar in milk, that can (for almost all mammal species) only be digested by infants or toddlers?”
An answer could be that it enforces weaning.
The reduction in lactase production in most mammal species coincides pretty closely with the weaning age.
Weaning prevents older animals from eating the food their infant siblings need.
So weaning benefits the species as a whole, which explains how lactose production combined with lactase production only in the youngest animals is present in mammals.
For humans, we have managed to get access to milk from other mammals, turning that mechanism on its head. Now it is beneficial for humans to continue to produce lactase past the weaning age since it increases our survivability.
It is not surprising that lactase should decrease in adults, since humans evolved before domestication of dairy animals. There was selective disadvantage to making an enzyme past childhood if adults did not drink milk. Those who turned off lactase in adulthood thus had a slight advantage over those who did not. That advantage is reversed today, but it is too soon evolutionarily to matter.
It seems to be not conclusively known, probably because determining similar enzyme levels is quite an invasive procedure (endoscopy).
Speaking as someone who became symptomatic with CSID later in life, the likely cause is that the enzyme levels (sucrase, maltase, isomaltase) dropped enough to become noticable.
Fetal hemoglobin is a good example (although hemoglobin is not really an enzyme). Before birth your hemoglobin needs to bind oxygen more strongly than your mom’s hemoglobin, so there’s a fetal specific version of the protein. This is switched off after birth.
One potential treatment of sickle cell disease is to switch fetal hemoglobin back on using gene therapy. See this study for example: https://www.nejm.org/doi/full/10.1056/NEJMoa2029392
The production of many/most/all(?) proteins, including enzymes, is more or less tightly regulated. In multi-cellular organisms most genes are used in specific “places” (cell or tissue types) at specific times. Very few genes are active in all cells at all times.
If you think about it, most of the ways that tight regulation might get screwed up (proteins not made in the right cells at the right time) means the organism dies. So lots of them don’t really produce disease states, they just cause miscarriages. The case of the lactase gene being deregulated (I.e. not being turned off after puberty) giving a benefit to humans in some cultures is very unusual for a gene. It only confers a benefit because some cultures domesticated mammals giving them life-long availability of milk.
Lactase is not special. There are other genes like that. Genes involved in embryonic development get turned off after a certain point. They play a role in a part of ebryonic development which once completed are turned off. Why this is done generally be because abnormal development would occur if they did not. Some of these when turned back on due to mutations play a role in cancer development. So that would be a clear example of genes being turned off after a certain amount of development. Age here of course is very early in development in utero but same concept. There are others but these are the ones that come immediately to mind.
The sucrase-isomaltase enzyme is generally pretty stable in adults, but some populations have a significantly higher number of people born without the enzyme. My understanding is that a higher number of indigenous people from near the Arctic circle (5-10% in Greenland, for example) are missing this enzyme. A CSID diet is often high in meat, which does not contain sucrose, unlike most grains and starches.
Also a gastrointestinal infection can sometimes cause a decrease in production.
The enzyme is found in the brush border of the small intestine. The microvilli come into contact with a sucrose molecule (or certain other saccharides) and then the enzyme grabs it and breaks it apart, passing the glucose and fructose to the blood stream. (Very simplified and there’s probably a more better way to describe it, but it’s late where I am and I’m spent.)
I wrote a book about it. Here is the essence:
Cavemen only eat lactose as breast milk as babies.
Cavemen grew up.. no more lactose
Evolution says.. let’s save energy and wind down lactase enzyme production if not needed.
Lactose Intolerant humans domesticate cattle
Mutation happens in one person in Scandinavia 6000 years ago. Not the gene is disrupted.. but the “switch off with age” element. He can drink milk in adulthood. So can his offspring
Famine kills many people over the last 6000 years
People with the mutation have dairy and milk as additional food source when others starve.
Higher likelihood to survive and spread the new mutation.
Today 80% of Germans carry the mutation and can drink milk.
They are the genetic freaks, not the norm.
This was a European phenomenon, plus the same happened somewhere in Africa independently. The rest of humanity is still the caveman norm.
So lactase is an outlier in the enzymatic activity with age. But my guess is any enzymes not needed in adulthood would show such a decline. Think embryonic development processes for example.
Somewhat related as part of your question is about body functions decreasing with age and one change that is explored in research for transplants and aging is https://en.wikipedia.org/wiki/Thymic_involution
our immune system gets weaker with age mainly because of this, although it isn’t an enzyme specifically like you asked.