Modern anti-aging treatment is built on a common base of knowledge that I will quickly review. Biochemistry and molecular biology tell us there are many types of chemical reactions going on in the human body. We know that it is the genetic information programmed inside our cellular DNA that defines what reactions occur. Genetic information, expressed in regulated ways, builds the body's proteins and enzymes, and controls how enzymes carry out the cell's biochemical reactions.
This information, contained in the DNA of our genome, consist of many thousands of long, often repetitive, sequences of base pairs that are built up from four basic nucleotides. Human genome mapping has shown there are over 3 billion base pairs in our DNA. It is estimated that they contain some 20,000 protein-coding genes. All body functions are controlled by the expression of the genes in our genome. The mechanisms controlling the aging process are believed to be programmed into our DNA but only a fraction of the biochemical reactions related to the aging process have been looked at in any detail. Cellular aging is a very complex process and many of its low level operating details have yet to be discovered.
Anti-aging theory has consolidated itself along two lines of thought: the programmed cellular death theory and the cellular damages theory. The programmed death theory focuses on the root causes of aging. The cellular damages theory looks at the visible aspects of aging; ie the symptoms of aging. Both theories are correct and often overlap. Both theories are developing rapidly as anti-aging research uncovers more details. As works in progress these theories may take years to complete. This broad characterization also applies to the currently available types of anti-aging treatments.
The programmed death theory of aging suggests that biological aging is a programmed process controlled by many life span regulatory mechanisms. They manifest them through gene expression. Gene expression also controls body processes such as our body maintenance (hormones, homeostatic signaling etc.) and repair mechanisms. With increasing age the efficiency of all such regulation declines. Programmed cellular death researchers want to understand which regulatory mechanisms are directly related to aging, and how to affect or improve them. Many ideas are being pursued but one key area of focus is on slowing or stopping telomere shortening. This is considered to be a major cause of aging.
With the exception of the germ cells that produce ova and spermatozoa, most dividing human cell types can only divide about 50 to 80 times (also called the Hayflick limit or biological death clock). This is a direct consequence of all cell types having fixed length telomere chains at the end of their chromosomes. This is true for all animal (Eukaryotic) cells. Telomeres play a vital role in cell division. In very young adults telomere chains are about 8,000 base pairs long. Each time a cell divides its telomere chain loses about 50 to 100 base pairs. Usually this shortening process distorts the telomere chain's shape and it becomes dysfunctional. Cell division is then no longer possible.
Telomerase, the enzyme that builds the fixed length telomere chains, is normally only active in young undifferentiated embryonic cells. Through the process of differentiation these cells eventually form the specialized cells from which all of our organs and tissues are made of. After a cell is specialized telomerase activity stops. Normal adult human tissues have little or no detectable telomerase activity. Why? A limited length telomere chain contains chromosomal integrity. This preserves the species more than the individual.
During the first months of development embryonic cells organize into about 100 distinct specialized cell lines. Each cell line (and the organs they make up) has a different Hayflick limit. Some cell lines are more vulnerable to the effects of aging than others. In the heart and parts of the brain cell loss is not replenished. With advocating age such tissues start to fail. In other tissues damaged cells die off and are replaced by new cells that have shorter telomere chains. Cell division itself only causes about 20 telomere base pairs to be lost. The rest of the telomere shortening is believed to be due to free radical damage.
This limit on cell division is the reason why efficient cell repair can not go on indefinitely. When we are 20 to 35 years of age our cells can renew themselves almost perfectly. One study found that at the age 20 the average length of telomere chains in white blood cells is about 7,500 base pairs. In humans, skeletal muscle telomere chain lengths remain more or less constant than the early twenties to mid seventies. By the age of 80 the average telomere length decreases to about 6,000 base pairs. Different studies have different estimates of how telomere length varies with age but the consensus is that between the age of 20 and 80 the length of the telomere chain decrees by 1000 to 1500 base pairs. Afterwards, as telomere lengths shorten even more, signs of severe aging begin to appear.
There are genetic variations in human telomerase. Long lived Ashkenazi Jews are said to have a more active form of telomerase and longer than normal telomere chains. Many other genetic differences (ex .: efficiency of DNA repair, antioxidant enzymes, and rates of free radical production) affect how quickly one ages. Statistics suggest that having shorter telomeres increases your chance of dying. People who telomeres are 10% shorter than average, and people whose telomeres are 10% longer than average die at different rates. Those with the sender telomeres die at a rate that is 1.4 greater than those with the longer telomeres.
Many advances in telomerase based anti-aging treatments have been documented. I only have room to mention a few of them.
– Telomerase has been used successfully to prolong the life of certain mice by up to 24%.
– In humans, gene therapy using telomerase has been used to treat myocardial infarction and several other conditions.
– Telomerase related, mTERT, treatment has successfully rejuvenated many different cell lines.
In one particularly important example researchers using synthetic telomerase that encoded to a telomere-extending protein, have extended the telomere chain lengths of cultured human skin and muscle cells up to 1000 base pairs. This is a 10% + extension of telomere chain length. The treated cells then showed signs of being much younger than the untreated cells. After the treatments these cells behaved normally, losing a part of their telomere chain after each division.
The implications of successfully applying such techniques in humans are staggering. If telomere length is a primary cause of normal aging, then using the telomere length numbers previously mentioned, it might be possible to double the healthy time period during which telomere chain lengths are constant; ie from the range of 23 to 74 years to an extended range of 23 to 120 or more years. Of course this is too optimistic because it is known that in vitro cultured cells are able to divide a larger number of times than cells in the human body but it is reasonable to expect some improvement (not 50 years but say 25 years).
We know that telomerase based treatments are not the final answer to anti-aging but there is no doubt that they can, by increasing the Hayflick limit, extend or even immortalize the lifespan of many cell types. It remains to be seen if this can be done safely done in humans.