Why Do Telomeres Shorten?

Telomeres naturally shorten each time a cell divides due to the so-called end-replication problem. The enzyme that copies your DNA (so that each daughter cell can get a full set after a cell divides) only runs in one direction, so when the double helix gets upzipped and opened, the DNA copying enzyme on one strand can zip along to the end, but the enzyme on the other strand can only copy in fits and starts in the opposite direction as the helix unfurls. It’s complicated to describe but the upshot is the final 50 or so letters of the DNA code on the lagging strand can’t be replicated.

Those final fifty letters could include critical genetic information that would get lost if it weren’t for telomeres, which are composed of thousands of repeats of the “nonsense” sequence TTAGGG. (If grade school biology is a long-lost memory, the four letters of the DNA alphabet are A, C, G, and T, which stand for adenine, cytosine, guanine, and thymine). Telomeres thereby pad the ends of our DNA with expendable letters. The reason I’m going into this seemingly unnecessary detail is to point out that fully half of all telomeric DNA is composed of guanine, the DNA letter most prone to oxidation.

Under conditions of oxidative stress in vitro, telomere shortening can jump tenfold from losing 50 letters per cell division up to 500. This is consistent with population studies showing a direct correlation between telomere length and the antioxidant capacity of people’s diets. Six out of eight human studies confirmed this relationship between oxidative stress and telomere shortness or shortening. In proliferative tissues, such as in the skin, gut, or bone marrow, the bulk of telomere attrition may be from the unavoidable per-replication loss, but in less rapidly dividing cells, such as those in the brain, heart, or liver, the ultimate uncapping of our DNA may be a result of free radical damage targeting all those triple G’s.

Why did our body choose to make our telomeres so vulnerable? Presumably because it allows our telomeres to play a further role as barometer for genotoxic stresses. This might offer a dual safeguard against cancer by stopping cells that divide too many times, along with those potentially mutated by too much DNA damage. The excessive oxidative erosion of our telomeres may be a proxy for genetic damage more generally throughout the chromosomes, so the arrest-in-replication safeguards against perpetuating mutations.

Anti-inflammatory diets are also associated with longer telomeres and a slower rate of telomere shortening. If you read the Oxidation and Inflammation chapters in How Not to Age, the types of foods linked to telomere protection should come as no surprise. A systematic review on the role of nutrition concluded that longer telomeres were associated with the intake of vegetables, fruits, legumes, nuts, and other foods high in fiber and antioxidants. In contrast, the consumption of processed meats, alcohol, soda, and other foods and beverages rich in saturated fat and sugar were linked to shorter telomeres. Men and women eating even just three servings of fruits and vegetables a day had more than four fewer years of telomere aging than those who didn’t eat any on a regular basis. Most studies were observational in nature but do suggest plant-based diets may be an effective tool for delaying telomere shortening. However, cross-sectional “snapshot in time” studies do not show significant differences in average telomere length between vegetarians and omnivores. The only way to know for sure whether a plant-based diet is protective is to, put it to the test.