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.

1. STRENGTH
2. CONSISTENCY
3. SPECIFICITY
4. TEMPORALITY
5. GRADIENT
6. PLAUSABILITY
7. COHERENCE
8. EXPERIMENTAL EVIDENCE
9. ANALOGY

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.