Telomere shortening causes aging!
I can make this statement but how do you objectively establish causation versus association? In epidemiology, we use the NINE BRADFORD-HILL criteria, which represent common sense rules of logic. The more of the criteria you have, the more likely something is actually CAUSING something else and not just associated.
- EXPERIMENTAL EVIDENCE
Anyone can come up with a theory. Here are some popular ones: the sun travels around the earth, gods roll dice to decide our destinies, evil spirits can cause madness.
By using the Nine Bradford-Hill criteria, we can assess causation for just about anything. Let’s say I have a theory that “having four wheels on a vehicle causes lethal motor vehicle accidents.” After all, almost all of the lethal MVA’s are associated with four-wheel vehicles. Intuition tells us this is association and not causation but let’s go through the process to show you how the criteria work:
STRENGTH – good. Most accidents involve cars with four wheels.
CONSISTENCY – again good, given most MVA’s involve passenger cars
SPECIFICITY – poor. Motorcycles and 18-wheelers are more lethal than four wheel accidents.
TEMPORALITY: fair. You usually need four-wheels to get into an MVA
GRADIENT: poor in either direction. Fewer wheels (Motorcycles) and more wheels (trucks) are more lethal.
PLAUSABILITY: poor. Why would four wheels do this?
COHERENCE: poor. Why would four wheels do this?
EXPERIMENTAL EVIDENCE: poor. NTSB tests have not been done comparing four wheels with two wheels because the outcome is obvious. Just ask any ER physician.
ANALOGY: poor. Who is more nimble, you or your dog or cat? Four legs, like four wheels is a good foundation.
What about the theory that telomere shortening causing aging?
STRENGTH – excellent. The older you are, the shorter your telomeres. The fastest shortening comes with premature aging syndromes (Progerias)
CONSISTENCY – excellent. All humans age and all humans show telomere shortening as they age.
SPECIFICITY – excellent. Shortening telomeres is a hallmark most of the Progerias
TEMPORALITY- good. Shortening telomeres occurs before aging appears
GRADIENT – excellent. The older you get, the shorter they get
PLAUSABILITY – excellent. Loss of protection of the ends of chromosomes allows for DNA rearrangement
COHERENCE – excellent. Loss of protection of the ends of chromosomes allows for DNA rearrangement and subsequent disease
EXPERIMENTAL EVIDENCE – Nature has done these experiments in the form of the Progerias which involve DNA repair deficiencies.
ANALOGY: excellent. Telomeres protect the tips like aglets on shoelaces. Another analogy is that aging chromosomes are like candles burning on both ends.