Zombie Cells: Another Contributor to More Rapid Aging and Chronic Illness
An Introduction to Cellular Senescence
The path to aging more rapidly and developing age-related disease is complex, but it is all tied together. If you care about keeping your health and being able to enjoy your loved ones and independence longer, no one thing will accomplish that, but a combination of diet, exercise, and certain precision medicines in a cohesive strategy can make a tremendous difference. Healthcare professionals call that optimal medical therapy (OMT). There is proof that a strategy like this prolongs human life by 8 years in individuals that are already older and sicker. We work with Vestra Health a worksite clinic that has reduced healthcare costs by half for a Native American tribe with optimal medical therapy as part of their offering. We can have better health at lower cost now.
I am learning all the time about the ways that aging and chronic illness are related. I had heard of Zombie (senescent) cells before, but I had not realized the critical role that they play in aging and chronic disease. There are many cells in our body that continue to divide and replace cells that line other organs. Skin is a perfect example. The lining cells of the digestive and vascular systems are other examples.
Dividing cells can only multiply a fixed number of times. There is a cap on the end of DNA called a telomere, and each time the cell divides, the telomere becomes a bit shorter. When that cell runs out of telomere, the cell stops dividing. It becomes senescent. Senescence has the same root as senile. The cell is old. That would not be so bad if the cell just sat there, but it does not. It becomes a cellular factory that puts out growth factors, oxidants, and inflammatory mediators. These in turn accelerate the process by which neighboring cells become senescent.
This process is very well worked out at an epigenetic and molecular level. Consider the example of ADMA. ADMA is formed as part of the process of switching on genes. ADMA formation is essential in fetal and childhood development. ADMA levels correlate with the growth rate in children. There it is a marker of health. It falls to its lowest levels in healthy young adults and then rises again with age. In that setting, ADMA levels correlate with all cause mortality.
ADMA significantly accelerated the development of cellular senescence in arterial cells. ADMA shortened telomere length and reduced telomerase activity. This effect was associated with an increase of oxidative stress. ADMA levels increase with age and cause cellular senescence.
Here is the good news! ADMA and metformin are structural analogs. That is, they look alike on one end. Metformin blocks the effects of ADMA at the membrane level. In keeping with its effect of blocking ADMA, metformin blocks the formation of senescent cells and the inflammatory mediators that they produce by increasing the enzyme that preserves telomere length. This is yet another way that metformin slows aging and reduces all-cause mortality.
Interleukin 1-B is a major inflammatory mediator produced by senescent cells and it switches on many other inflammatory mediators downstream. Metformin reduces Interleukin 1-B effects for $4 a month. You can pay a lot more for a medication that reduces interleukin 1-B (IL-1B) and have more side effects for your trouble. Canakinumab is a monoclonal antibody against 1-B that causes fatal infections and sepsis. This drug does reduce cancer deaths but provides no benefit for all-cause mortality. Canakinumab displayed beneficial effects for arthritis, gout, and osteoarthritis. Canakinumab and metformin both lower IL-1B. Canakinumab costs $73,000 a year. Metformin costs $10 for 90 or $40 dollars a year. Metformin is safer and has more wide-ranging benefits. Canakinumab reduced the risk of a cardiovascular event by 15%. A protocol containing metformin reduced the risk of heart attack 4-fold and reduced all-cause mortality. Metformin may be the most valuable, safest drug in the entire medical toolbox.