In yesterday’s post, I wrote about the fact that different parts of our bodies keep regenerating themselves periodically. This fact alone should make nonsense of the belief of some religious people that our bodies become physically reconstituted after death in the afterlife, because if so, the resurrected body of a person who died at the age of 70 would be unrecognizably grotesque, consisting of around 70 livers and 7 full skeletons, all surrounded by hundreds, maybe thousands, of pounds of skin.

But leaving aside that, there is an interesting question raised by this constant regeneration of the body and that is how we retain a sense of having a single identity over our full life spans even as individual parts of us get replaced periodically. The average age of the molecules in my body is around 7 to 10 years and yet I have the strong sense of continuity, that I am in some fundamental sense the same person that I was as a child, even though almost none of those molecules have stayed with me over that time. How is it that we retain a strong sense of permanence in our identity while being so transient in our bodies?

The answer may lie in the fact that our brain seems to be the most permanent of our organs, undergoing little or no regeneration. In the same article in the New York Times that I referred to yesterday, Nicholas Wade says:

Dr. Frisen, a stem cell biologist at the Karolinska Institute in Stockholm, has also discovered a fact that explains why people behave their birth age, not the physical age of their cells: a few of the body’s cell types endure from birth to death without renewal, and this special minority includes some or all of the cells of the cerebral cortex.

The cerebral cortex is the thin sheet that forms the outer layer of the brain and is divided up into several zones that have different functional roles. If the cortex were removed and smoothed out to eliminate all the creases and folds, it would look like a dinner napkin. It is gray in color, the origin of its popular euphemism of ‘gray matter’. The network of nerve cells in the brain (called neurons) determines how the brain functions.

While the brain seems to be the most enduring part of the body, even here there is variation. The cerebellum seems to contain non-neuronal cells that are close to the birth age (within three years or so) while the cerebral cortex (which is responsible for our cognitive capabilities and is thus most closely identified with our sense of self) has a slightly greater turnover of non-neuronal cells. But the researchers do not turn up any evidence that there is neuronal generation after birth, at least in the region known as the occipital cortex.

It was long believed that the number of neuronal connections in the brain grew rapidly during the first year or two of life and then got pruned and this was how our lives shaped our brains without new neurons being created. In 1999, there was research that found that new neurons were being created in the cerebral cortex of adult monkeys, suggesting that it could happen in adult humans too. This would complicate things somewhat as to how we retain a permanent sense of self but also provide hope that brains could regenerate. But this summary of later research (much of it by the same Karolinka group that I referred to yesterday) that appeared in the Proceedings of the National Academy of Sciences says that this does not happen with the neurons in the human cerebral cortex. (The neocortex referred to in the paper is the most recently evolved part of the cortex that is defined as containing the ‘higher’ functions and are “arranged in six layers, within which different regions permit vision, hearing, touch, the sense of balance, movement, emotional responses and every other feat of cognition.”)

The results show that the average age of the neurons (with respect to the age of the individual) is age 0.0 ± 0.4 years, i.e., the same as the age of the individual. In contrast, the nonneuronal cells have an average birth date of 4.9 ± 1.1 years after the birth of the individual.
…
Both of the experiments of Bhardwaj et al. indicate that there are no new neurons, either long-lived or transient, produced in the adult human for the neocortex. Importantly, these experiments are quantitative and indicate a theoretical maximum limit of 1% on the proportion of new neurons made over a 50-year period.
…
Bhardwaj et al. settle a hotly contested issue, unequivocally. The two-pronged experimental approach clearly establishes (i) that there is little or no continuous production of new neurons for long-term addition to the human neocortex and (ii) that there are few if any new neurons produced and existing transiently in the adult human neocortex. Importantly, the results are quantitatively presented, and a maximum limit to the amount of production of the new neurons can be established from the data presented. The data show that virtually all neurons (i.e., >99%) of the adult human neocortex are generated before the time of birth of the individual, exactly as suggested by Rakic, and the inescapable conclusion is that our neocortical neurons, the cell type that mediates much of our cognition, are produced prenatally and retained for our entire lifespan. [My italics]

So basically, even though every other part of us gets sloughed off and replaced at different points in time, for good or bad we are pretty much stuck with the brains that we have at birth. This may be crucial to our ability to retain a sense of a permanent identity that lasts all through our lives, although this is not yet established. Even if new research emerges that new neuronal cells could be generated over time replacing older ones, it may turn out to be able to do this seamlessly and provide cognitive continuity, just the way our other organs give us the illusion of being permanent even though they are not.

It seems like our brains are our essential selves with the rest of our bodies just superstructure. Rene Descartes famously said “I think, therefore I am.” We could also say, “My brain is who I am.”

Now that computers have beaten us at chess, robots are turning their attention to pool.

(Via Machines Like Us.)

In an article in the New York Times, Nicholas Wade points out that our bodies are younger than we think, because there is a discrepancy between our birth age and the age of the cells that make up our bodies

Whatever your age, your body is many years younger. In fact, even if you’re middle aged, most of you may be just 10 years old or less.

This heartening truth, which arises from the fact that most of the body’s tissues are under constant renewal, has been underlined by a novel method of estimating the age of human cells. Its inventor, Jonas Frisen, believes the average age of all the cells in an adult’s body may turn out to be as young as 7 to 10 years.

He quotes the work of Spalding, Bhardwaj, Buchhold, Druid, and Frisén of the Karolinska institute that uses the radioactive isotope carbon-14 to determine the age of the cells in bodies. Their paper appeared in the July 15, 2005 issue of Cell. They used carbon-14 dating to determine the age of cells. The carbon that forms organic matter is largely obtained from the atmosphere. Plants, for example, take in carbon dioxide from the air and exude oxygen as part of the process of photosynthesis. Hence the proportion of carbon-14 that is found in living organic matter is the same as that in the ambient atmosphere at the time it was absorbed. The level of the radioactive isotope carbon-14 that occurs in the atmosphere is fairly constant because its rate of production is balanced by the rate of decay. Once the plant dies, it does not take in any new carbon and the decay of the carbon-14 that it had at the moment of death results in a steadily smaller proportion of it and the difference can be used to measure how long it has been dead. The half-life of carbon-14 is 5,730 years and this method can be used to determine the age of dead organic matter up to about 50,000 years, which is a convenient range for archeological dating because it lies in the range required for those studies.

The way that Frisén and his co-workers used this knowledge to measure the age of cells in humans is quite clever. Carbon-14 is produced by cosmic rays and the level of carbon-14 in the atmosphere should be constant. This is why we can tell how long something has been dead but not when it was ‘born’, i.e., when the organic matter was created. But in the 1950s and 1960s, there was a sharp spike in carbon-14 levels because of the atmospheric testing of nuclear weapons. Once atmospheric test ban treaties came into came into being, the surge of carbon-14 that had been produced steadily became diffused in the atmosphere as it spread over the globe, and so there has been a steady decline in average carbon-14 levels over time. It is this that enables us to know when the carbon-14 was absorbed to create organic matter.

The amount of carbon-14 in the genomic DNA can thus be used to measure when the DNA in the cell was created. The technique was checked against the age of trees which can be measured by the amounts of carbon-14 found in the various rings as the isotope is absorbed during photosynthesis. Their results and those of others show that different parts of the body get replaced after different durations, whose approximate values are given below. (I have included results from both the Wade newspaper article and the Frisen paper.)

Stomach lining: five days
Surface layer of skin: two weeks
Red blood cells: three months
Liver: one year
Skeleton: 10 years
Intestine: 11 years
Rib muscles: 15 years

This explains why our bodies seem so durable and able to withstand considerable abuse. [UPDATE: Later studies find that about 50% of our heart muscles are replaced over our lifetime, but the brain cells seem to be largely unchanged.]

So why do we die if parts of us keep getting regenerated? It seems as if the ability of stem cells to keep reproducing declines with age. In other words there seems to be a limit to the number of times that cells can reproduce and once we reach that limit, the ability of the body to regenerate itself ceases. What causes this limit is still an open question. As Wade writes:

Some experts believe the root cause is that the DNA accumulates mutations and its information is gradually degraded. Others blame the DNA of the mitochondria, which lack the repair mechanisms available for the chromosomes. A third theory is that the stem cells that are the source of new cells in each tissue eventually grow feeble with age.

Frisen thinks his research might be able to shed some light on this question, especially the third option, saying “The notion that stem cells themselves age and become less capable of generating progeny is gaining increasing support.”