How Time Reveals the Secrets to Longevity

by | Jun 16, 2022

The Power of Selective Survival

Many years ago my 85 year old mother and 90 year old father were at dinner with my wife and I. When the meal was over, the time arrived to decide whether to have dessert. Mom looked down at her pudgy self and declared, as she had every night for the previous seven decades, that she needed to begin watching what she was eating in order to lose weight.

As a professor of public health, you might expect my first reaction would have been to agree with her. Decades ago, yes, but at her age my reaction was the exact opposite. I said Mom, if carrying excess weight was a harmful risk factor for you – you’d be dead already. Go ahead and enjoy dessert, just not in excess. She did just that, with a sense of relief I might add.

This paradox is an example of a public health phenomenon known as “selective survival”. That is, the passage of time uncovers subgroups of the population with unique attributes that enable them to live long. Selective survival is also the reason why some now suggest that Covid-19 culled the weaker and more frail members of humanity with pre-existing health conditions – leaving behind a more robust population that could yield a post-Covid life expectancy rebound.

These unusual and often rare survivors are interesting because they’re somehow protected from a relentless and well established lethal risk factor, such as smoking.

The picture above is the documented longest lived person in history – Jeanne Calment from France. She died in 1997 at the age of 122, and she smoked for more than a century.

For the same reasons, this is also why many researchers in the field of aging like to study the genetics of centenarians – because time shines a spotlight on them as beacons of hope as researchers scramble to understand what’s different about these people, and whether it’s possible for science and medicine to discover and then find a way to confer their survival advantage on the rest of us.

Consider a hypothetical experiment where we start out with 1 million babies born in a given year, and half of them are required to begin smoking by age 10 while the other half remain nonsmokers throughout life. The average duration of life for the smokers would be many years shorter than the nonsmokers. However, 100 years after this otherwise fateful experiment, time would reveal a small percentage of the original half million smokers still alive 90 years later, for whom smoking was never a risk factor to begin with.

This is how selective survival operates. Ironically, this is also how evolution works. Differences in survival (and fertility) reveal population subgroups with different risk factors and survival prospects.

Some people survive to extreme old age carrying with them a lifetime of behavioral risk factor baggage that tends to kill everyone else at a much earlier age. These folks smoke cigarettes, drink excessively, eat large amounts of fat; etc. Basically, everything your doctor and mother tell you that you shouldn’t be doing. Yet they survive anyway. This is the main reason why a generic approach to survival analysis where people with certain risk factors are all treated exactly the same – using a common mortality multiplier – will often lead to grossly incorrect estimates of survival. The bottom line is that people experiencing exceptional longevity often do not exhibit healthy lifestyles, which tells you there are other reasons why they live so long. Genetics!

This brings me to a recent scientific discovery: “We may finally know why so many lifelong smokers never get lung cancer”. The secret is in their genes. There is a group of cells in our lungs known as bronchial epithelial cells that accumulate genetic damage every time they divide. These are the cells most likely to transform into cancer cells within the lungs and they’re the primary cells involved in lung cancer. The process of transforming bronchial epithelial cells into cancer cells is determined by the amount of abuse we exact on our lungs during the course of life (either on purpose or by accident), and the level of DNA repair that operates within those cells.

In a study of exceptionally long-lived lifelong smokers compared with younger people – including both smokers and nonsmokers; it was discovered that the long-term smokers that survived to extreme old age experienced genetic mutations that slowed considerably after about 23 years of tobacco abuse. That is, they had exceptionally powerful DNA repair mechanisms that were so effective, they eliminated or dramatically delayed the risk of lung cancer – even in the presence of decades of self-inflicted tobacco abuse.

It is believed that these highly efficient DNA repair mechanisms are inherited, although some scientists suggest that highly efficient DNA repair can be an acquired trait – but researchers are still working out the details.

Either way, we now think we know how some people can live so long after decades of inhaling toxic substances that kill the rest of the population at a much younger age. Although we’re nowhere near determining in advance, at younger ages, whether you’re a member of the population subgroup that has superman DNA repair in bronchial epithelial cells, that time might not be far off.