Let’s start with a stylized fact: almost every cell type in the human body is removed and replaced on a regular basis. The frequency of this turnover ranges from a few days (for many immune cells and cells in the gastrointestinal lining) to ten years (for fat, heart, and skeleton cells). Only a handful of tissues are believed to be non-renewing in humans - e.g. eggs, neurons, and the lens of the eye (and even out of those, neurons are debatable).

This means that the number of cells of any given type is determined by “homeostatic equilibrium” - the balance of cell removal and replacement. If an ulcer destroys a bunch of cells in your stomach lining, they’ll be replaced over a few days, and the number of stomach cells will return to roughly the same equilibrium level as before. If a healthy person receives a bunch of extra red blood cells in a transfusion, they’ll be broken down over a few months, and the number of blood cells will return to roughly the same equilibrium level as before.

As organisms age, we see a change in the homeostatic equilibrium level of many different cell types (and other parameters, like hormone and cytokine levels). In particular, a wide variety of symptoms of aging involve “depletion” (i.e. lower observed counts) of various cell types.

However, human aging happens on a very slow timescale, i.e. decades. Most cell counts equilibrate much faster - for instance, immune cell counts equilibrate on a scale of days to weeks. So, suppose we see a decrease in the count of certain immune cells with age - e.g. naive T cells. Could it be that naive T cells just wear out and die off with age? No - T cells are replaced every few weeks, so a change on a timescale of decades cannot be due to the cells themselves dying off. If the count of naive T cells falls on a timescale of decades, then either (a) the rate of new cell creation has decreased, or (b) the rate of old cell removal has increased (or both). Either of those would require some “upstream” change to cause the rate change.

More generally: in order for cell counts, or chemical concentrations, or any other physiological parameter to decrease/increase with age, at least one of the following must be true:

the timescale of turnover is on the order of decades (or longer)
rate of removal increases/decreases
rate of creation decreases/increase

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Bill Walker

Bill Walker

Bill Walker

Bill Walker