Why We Age
Life expectancy in pre-industrial society, and the biology of aging
[I plan to pursue the ‘aging’ thread in several essays to come, but not necessarily back-to-back. Take this essay as the first installment.]
Flabby bodies and swollen legs – Live fast but don’t die young – Crash course in Molecular Biology – Strictly for biology nerds, and everyone
Flabby bodies and swollen legs
I witnessed two of my grandparents grow old and die, and it was not pretty. Flabby bodies, weak/lost eyesight, involuntary defecation, swollen bodies, you name it. It isn’t good. And that has been the fate of many who had lived before us and many folks today.
But truth be told, it is awfully better now, as far as lifespan goes. And this junction will be my first stop.
Live fast but don’t die young
From the ancients to the pre-industrial society (<1850), there is a rough consensus that global life expectancy at birth is just a paltry 30-35 years. Now, this doesn’t necessarily mean most people die at 30 or 35. But given the high infancy death rate, that average is bound to be that low.
Fast forward to 1913, and it’s about thirty-four. Fast forward again to the year I finished college, 2012: it was seventy-one years old. Those are global averages, so we are sure a few details are bound to be masked, but to really appreciate the point here, take one of the poorest countries today, Mozambique. The life expectancy at birth of a Mozambican in 1960 is thirty-nine years. Today, it’s a little over sixty.
Ok. And what do we do with this? For one, this is a remarkable feat, increasing life expectancy over that short period of time without any real concerted effort to do so. Without any age-extending elixir or genetic engineering.
Well, for one, we took care of child mortality. For our predecessors, one in four children dies before their second-year birthday, as if that was not enough; one in two folks died before puberty.
So came antiseptics, effective sewage system, clean running water, vaccination, et cetera. And it might be helpful to think that the advice of handwashing was once a piece of controversial advice. Okay, short story (which you might know).
In the 1840s, puerperal fever was plaguing women in the maternity ward in Europe, leaving many of them dead shortly after birth. A Hungarian physician, Ignaz Semmelweis, investigated the problem, noticing that maternity wards manned by doctors and medical students had a higher mortality rate than those handled by midwives.
After ruling out many other factors, he noticed that doctors and medical students report to the maternity ward after autopsy while midwives had no such obligation beforehand. He hypothesized “cadaverous particles” being transferred from cadavers to new mothers (the germ theory of disease was yet to be fully developed at the time!) So, a mandatory handwashing regimen was instituted, and surprisingly the death rate plummeted, basically reversing the death.
Despite the evidence and data right in front of their very eyes, Ignaz's theory was rejected by the medical community at the time, until folks like Joseph Lister espoused the idea of hand sanitation and cleaning of surgical instruments, and Louis Paster’s work on the germ theory. Even at that, hand washing wasn’t accepted universally until more than a century later.
Or we could take vaccination, which definitely saved A LOT of lives, and what a ridiculously beneficial invention. (Side note: my grandma was part of a team that embarked on one of the first attempts to eradicate measles from an African town in Southwestern Nigeria).
In the final analysis, the important point to make is that most of the deaths pre-industrial revolution aren’t because of aging. It is usually because of some pathogen that we didn’t know how to get rid of – who could have thought we were plagued by a biological agent we couldn’t see. But today, now that we have some handle over that, we are growing enough to die of age-related diseases, i.e., aging.
Crash course in Molecular Biology
Which begs the question, why do we even age?
One of the most prominent theories of aging is the information theory of aging championed by the biologist David Sinclair. It simply argues that we grow old because of the accumulation of genomic instability.
And it happens like this: As one grows older, DNA – the building block of our genetic material – breaks, leading to genomic instability. This, in turn, leads to the disruption of the epigenome.
And how does this happen? First, let’s make the distinction between DNA, gene, genome, epigenome, and all such molecular biology buzzwords. These terms will be used a lot in the upcoming explanation.
If you want to spell it all out, DNA is deoxyribonucleic acid. It is a molecule that contains our genetic code, and it is the building block of our genetic material. Next, gene. It is just a chunk of DNA that codes for a protein (a biological factor that does work in your cell.) We also have histones, which are particular types of proteins that package the DNA in the chromosome and make it fit into a tiny cell. On the other hand, the genome is the totality of the DNA in a cell, while the epigenome are chemical tags that mark the genome and histones, literally dictating what gene is to be expressed (into a protein) or not.
A way to think about this is to note that the genetic material in all the cells in your body are identical. So what differentiates your liver from your kidney is the differential expression of genes which are dictated by these chemical tags (the epigenome).
And if it will help, the genome is like your computer, and the epigenome – the software that goes on it.
Strictly for biology nerds and everyone
So back to explaining aging, when the DNA breaks, it mustn’t be surprising then that epigenome will be affected since they tag the DNA and histones at specific locations, and an unwinding procedure will have to follow to allow for DNA repair if such areas are affected. In addition to the fact that epigenetic factors are recruited to the location of damage for DNA repair operations.
At least two things will be adversely affected here, especially when there are a lot of fires to put out in the cell: DNA packaging and gene regulation. DNA packaging because it is the chemical tags on the genome that helps coordinate DNA packaging in a systematic way into a cell. And gene regulation because these chemical tags dictate what gene is to be expressed or not.
When this genomic and epigenomic instability mounts over time, the loss of cellular identity ensues (because the accurate genetic expression for a particular kind of cell is compromised). So genes that are supposed to be switched off go on; those supposed to be on get switched off.
For example, because of the chaos in the system, the kidney cells can now begin to act up like a, part brain cell, part skin cell.
In this conception, this gradual accumulation of DNA breaks due to the passage of time (mistakes from regular DNA copying), radiation, nasty chemicals, etc., leads to disease and hence death.
References, Recommended Readings
Biophysics, 2017, Vol. 62, No. 5, pp. 829–835.
Curr Genomics. 2017 Oct; 18(5): 385–407.
Scale: The Universal Laws of Life and Death in Organisms, Cities and Companies by Geoffrey West, Chapter Four
Lifespan: Why We Age―and Why We Don't Have To by David A. Sinclair, Chapter Two.