When we talk about “longevity,” what we are really referring to is a delaying of the aging process. Aging is an unavoidable process of nature, but we now know that the rate of its development is variable. Today the anti-aging arena is a big business – spending in this area is projected to reach a whopping USD $42 billion in 2007. We are now constantly bombarded with marketing messages about anti-aging creams and anti-oxidant tablets and other purported longevity enhancing pills and potions. However, do any of them really work? How much does our lifestyle influence our longevity?
To answer these questions properly, we must examine the scientific research, which includes data on human longevity throughout history and the more cutting edge molecular research of the last couple of decades.
As we look back through human history, we see that our average lifespan has pretty much improved since accurate records began, but that maximum lifespan has stayed pretty much consistent, at around 115 to 120 years. The average lifespan has increased from around 22 to the early 40s by the mid 1800s and has peaked at between 70 and 80 in developed countries today. These increases are due to a combination of factors: reductions in infant mortality rate, eradication of major disease epidemics and, more recently, better treatments for degenerative diseases.
As our understanding of the inner workings of the human body has improved, a lot of theories have been put forward to explain the mechanisms of aging, and they have varying degrees of scientific support. Amongst all of this research, a few leading theories have emerged:
- Telomere shortening
- Free radical damage
- Hormonal decline
Let’s take a brief look at these theories in order to establish mechanisms by which we can counteract them… or at least minimize their impact.
This theory is all about cell-cycle control. The body is basically a huge ecosystem of around 50 to 70 trillion cells that interact to make us function the way we do. However, all of our cells have a finite life span (the longest living cells in the body are liver cells, which last around two years, whereas half the mass of your heart is renewed every 40 to 45 days) and are “programmed” to die at a certain point in time. A process known as cell division (sometimes call Mitosis) is what keeps us alive and healthy. What basically happens is that the cell “divides” just before it dies, “giving birth” if you like, to two daughter cells, which help the body to stay healthy and intact.
Cell-cycle control is the whole process of cell division and cell death, and telomeres play a key role in this. They do this by protecting our chromosomes that encode our DNA, which subsequently ensures that the daughter cells are "born" with the right characteristics. Think of telomeres as the glue on the end of your shoelaces: with each act of cell division, the telomeres become a little shorter. When they become too short, the chromosomes get damaged (the shoe lace starts to unravel), and this results in DNA damage, which ultimately results in aging.
Good evidence for the critical impact of telomeres on the aging process can be seen with the congenital disease Progeria. The telomeres of the cells of affected individuals are "shortened" at a very early age, to such an extent that Progeria sufferers generally die of "age-related" illnesses by the time they reach puberty. Further evidence of the importance of telomeres is emerging from AIDS victims. The telomeres of the CD8 lymphocyte (critical in immune system functioning) are equivalent in length to those of the average 100 year old person, meaning the immune system is barely functioning.
Free Radical Damage
Free radicals are unstable molecules (for science buffs, they are lacking an electron) that are created in our bodies through oxygen consumption and the metabolism of fats, carbohydrates and protein. It’s therefore obvious that there’s a significant amount of free radicals within the body. In fact, each cell in the body produces around two to three billion free radicals per day. When you consider that the average human body contains between 50 and 70 trillion cells, that’s an awful lot (between 100 and 200 trillion) of free radicals roaming around the body. Normally, that’s not a problem as the human body has a sophisticated defense mechanism to either prevent the free radicals from creating damage or to counter their damaging effects.
However, if we produce too many free radicals or have a poor defense system, these free radicals roam unchecked throughout the body and attack molecules by stealing electrons from them. This then makes the victim molecule unstable, and this damage can spread like a domino effect.
So, how are free radicals produced and how can we defend against them?
There are two sources of free radicals:
- Endogenous – Produced inside the body, both from by-products of normal metabolism and from by-products of the body’s immune system
- Exogenous – From pollution, cigarette smoke, radiation (sun, X-rays, etc), certain foods (especially processed) and excessive alcohol consumption.
As mentioned previously, our bodies have a highly developed, layered anti-oxidant defense system to combat the harmful effects of free radicals.
- Prevention – This system works by inactivating molecules that are likely to produce free radicals such as certain trace metals within the body.
- Enzymatic anti-oxidants – This is the keystone of our anti-oxidant defense system. They are enzymes that are located within the cells and neutralize free radicals as soon as they appear. Our genetics largely determine how robust this system is, and as we age, our cells make inferior copies of the enzymes, giving free radicals more opportunities to create damage.
- Chain-breaking anti-oxidants – These are obtained from our diet and work by neutralizing free radicals that have escaped through the other two lines of our defense. Vitamins A, C and E, the mineral Selenium and bioflavanoids (from fruit and vegetables) are all examples of these types of anti-oxidants.
If the anti-oxidant system fails to neutralize any free radicals, we have other layers of defense:
- The P53 gene produces a protein (imaginatively named the P53 protein) that repairs "coding" DNA that has become mutant due to attack by free radicals (if "non coding" DNA is attacked, there are no genetic mutations).
- Our immune system contains natural killer cells that roam throughout the body, seeking and destroying mutant cells that have slipped through all previous layers of defense.
Very strong evidence for the free radical theory of aging comes from laboratory experiments where the control of free radicals can extend the life of multi-cellular organisms up to six-fold. This is augmented by research conducted by Dr. Pearls from the Harvard Medical School, who found the Centegenerians (those over 100) had much higher than average levels of blood anti-oxidants.
This is increasingly recognized as one of the key processes in the development of degenerative diseases and the aging process, as it occurs at a cellular level. Basically, when our cells get sick, we get sick. Paradoxically, it is also the mechanisms by which the body protects itself, as our immune system fights foreign invaders, infections and injury by releasing inflammatory agents. This inflammation creates stiffness and swelling to maximize the time for immune cells to do their job.
The key variable, in terms of the impact on our health, is the duration of the inflammation. When the underlying cause of the inflammation is not removed, the inflammatory response becomes chronic (long term). Most degenerative diseases – such as Cardiovascular Disease, Diabetes, Cancer, Parkinson’s disease and Alzheimer disease – are now thought of as being at least partly caused by chronic inflammation. This is why age researchers say that one of the best ways to improve longevity is to stay free of illness a much as possible, not because minor illness and infection kill us, but because they induce a state of inflammation, and there appears to be a cumulative effect.
So, what are the major culprits in terms of inflammation? Free radicals are a major cause, as are the following, which may cause inflammation directly or indirectly through production of more free radicals:
- Cigarette smoke
- Over exposure to radiation
- Exposure to drugs and chemicals
- Trans fats and chemicals in processed foods
- Elevated blood sugar
- Excess weight (especially fat around the stomach)
- Nutritional deficiencies (such as vitamin D)
- Nutritional excesses (such as Iron)
- Sleep deprivation
Recent research is focusing on the importance that age-related changes in our hormonal profiles have on our longevity. As we grow older, some of our hormones undergo a steep decline that has very strong parallels to many of the signs and symptoms of aging. These hormones include DHEA, Estrogen, Human Growth Hormone, Progesterone and Testosterone. Within the brain, there are age-related declines in certain neurotransmitters (Dopamine, Acetylcholine, Norepinephrine, GABA and Serotonin), which reduce cognitive function and impact on our quality of life.
To better understand the effects of these hormonal changes, let’s take a brief look at their roles within the body:
- DHEA – The building block for estrogen and testosterone, it also acts to boost our immune system and brain function.
- Estrogen, Progesterone and Testosterone – These are often referred to as the sex hormones, but they do much more than provide sex drive. They help to build muscle, bone and connective tissue, keep us mentally alert and protect us from heart disease.
- Human Growth Hormone – This is often referred to as the "longevity hormone" due to its anabolic (growth and repair) effects on the body. It stimulates our bones, nerves, muscle, skin and organs to regenerate, and it full effects are not yet completely understood.
- Together with these declines, two hormones that act to accelerate aging tend to increase as we get older: insulin and cortisol.
- Insulin – High levels of circulating insulin generally leads to insulin resistance in our cells. When this occurs, blood glucose levels tend to become chronically elevated. As well as pre-disposing us to diabetes, this leads to damage of body tissues by nasty substances known as advanced glycation end-products – fittingly abbreviated to "AGEs."
- Cortisol is the major stress hormone of the body and chronically elevated levels lead to numerous negative effects such as increased inflammation, weight gain, lowering of basal metabolic rate, suppressed immune function and unprogrammed cell division.
In Part 2, we will tie all of this together and discuss what it all means in the longevity process.