During my many years of directing a research and development (R&D) program for a biotech company that developed drugs to treat cancer, I was struck by the following observation:

The biological and biochemical pathways that regulate nutrition and energy balance of normal cells also play key roles in the development of cancer.

Furthermore, inflammation, another complex series of biologic pathways that help our bodies fight off infections and combat cancers (among other things), is also related to the biochemical pathways involved in the development of cancer and the regulation of energy metabolism. Whew…things are never simple.

In future posts, I will attempt to shed light on this intriguing confluence of biological states. In the process, I hope to share with you information about an area of research that, in the not too distant future, might help us identify the keys to longevity. What is really exciting about this line of research is that we may be able to learn not only how to extend life, but also how to help people live healthy lives as well.


So, why do we have to die anyway?

As far as I have been able to determine, there are no genetically embedded instructions for an individual to just lie down and die. Biologically, the death of an individual occurs after many of his or her cellular components die. That occurs as a result of a slow accumulation of damage to key components of the cells (amongst other things):

  • Degradation of cell membrane lipids
  • Damage to proteins that perform critical functions in the cell
  • Mutations in the genetic code (DNA) that result in impairment of the works of the enzymes and structures of that cell.

Once the level of damage or the number of mutations in a cell reaches a critical level, or an especially damaging mutation happens, the affected cell literally commits suicide (a phenomenon called apoptosis—pronounced “a-pop-toe-sis”). This occurs because the damage causes the cell to activate a predetermined set of “killer enzymes”.

If enough cells die in a particular organ of the body (say the kidney or liver), the organ cannot perform its function. That results in what we, physicians, call “organ failure”. When key organs, such as the heart, lungs, or liver, can no longer perform their duties to the body, the whole body begins to fail and the individual eventually dies.

So, what we see clinically is the following:

  • When enough heart muscle cells die, the heart fails and can no longer pump blood (and oxygen) to the rest of the body’s organs and tissues.
  • When a large number of kidney cells die, the kidney fails and can no longer cleanse impurities and toxins from the body.

When several organs fail at the same time, we label the condition “multi-organ” or “multi-system failure”. This is a dangerous state for humans. It frequently leads to death.


Historical human life expectancy

We actually live a lot longer now than we used to, even 100 years ago. In fact, when Social Security was established during Franklin Roosevelt’s administration just a few generations ago, actuaries calculated that most people would not survive much past age 65. This is how “retirement age” was determined.

Most historians agree that in the Middle Ages, life expectancy was about 40 years old. Now, people are living longer and, at least some of them, are living better. So you frequently hear people say that being 40 today is like being 30 in our parent’s day. And being 60, well, it’s like being 40—downright middle-aged (even though human beings are not yet living to be 120).

This improvement in lifespan, as impressive as it is, was not accomplished with any spectacular breakthroughs in understanding the mechanism of longevity. It occurred, rather, because of public health interventions that prevented early death:

  • Better nutrition
  • Better hygiene
  • The development of antibiotics to control infectious diseases


What can we do now to increase human life expectancy even more?

In the present day, a lot of premature death is due to our modern lifestyle:

  • We consume too many calories.
  • We burn too few calories.
  • We eat stuff that is bad for us (e.g., trans fats).
  • We smoke cigarettes.
  • We engage in unhealthy or unsafe activities.

We should be able to increase life expectancy by changes in our collective lifestyle. For example, forgoing cigarette smoking. Toxins in cigarettes damage our lungs, our hearts, and many other tissues. In fact, cigarette smoke also causes mutations in our DNA that sooner or later may be expressed as cancers of different organs.

Another example of lifestyle changes that could be altered to improve longevity is the recent epidemic of obesity. Genetically susceptible people develop insulin resistance and a whole host of related medical conditions, such as high blood pressure, abnormal lipids, heart disease, stroke, and type 2 diabetes (and its associated complications of blindness, numbness, kidney disease, and other bad things) when they accumulate excess abdominal fat. We are now in the midst of an epidemic of obesity and type 2 diabetes of an unprecedented scale. It is predicted that the obesity epidemic could result in our children’s generation having a shorter lifespan than our present generation. It would be the first time in many, many years that longevity would decrease instead of increase.


The Methuselah Factor – Can we live to 120 or more?

Suppose, in a “perfect world” with “perfect people”, we were able to conduct ourselves as “perfect saints?” What, then, would be our life expectancy? Actuaries have calculated that perfectly behaved human beings could live to be between 100 and 120 years. Not too shabby.

But is it good enough? Methuselah, a well-known biblical figure (Genesis 5:27) allegedly lived to be 969 years old. Even assuming that Methuselah was God’s favorite creature (after all he was Noah’s and Abraham’s forefather) and that he had a “perfect” lifestyle, he should only have been able to make it to ripe old age of 120 years as the bible bequeathed to us mortals.

Is it possible to live to be 900 years old or longer? The answer is “yes” according to many serious longevity scientists. They believe (and hope) that once we unravel all of the complexities of biologic pathways that control cell life, cell aging (senescence), and cell death (apoptosis), we may be able to extend life expectancy to extents unimaginable today.

In fact, longevity scientists are already accomplishing many incredible feats of life extension in a variety of (non-human) organisms. Intrigued? Well, you will have to wait to learn more about that by reading my next TDWI post. Stay tuned. This a fascinating area of science.

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.