Telomeres and Aging: The Role They Play in Disease, Lifespan, and Health

Found at the ends of your chromosomes, telomeres are essential regulators of cell division, impacting how cells age. Telomeres protect the ends of chromosomes and allow them to safely replicate during cell division. Without them, our cells would lose crucial DNA each time cell division occurs. Telomere length plays an important role in our lifespan and overall health, as shorter ones are linked to disease and a reduced lifespan.

Telomeres: What are they?

Telomeres are the tiny structures at the ends of the chromosomes consisting of repeating DNA sequences bound to a protein complex. In vertebrates, the repeating DNA sequence is TTAGGG where T, A, and G are the bases thymine, adenine, and guanine, respectively. Telomeres protect human genetic material from degradation and the chromosomes from sticking to each other.

The length of telomeres in a newborn range from 8,000 to 13,000 base pairs, but cells lose telomeres with each division. Fast-dividing cells such as liver cells may lose up to 55 base pairs per year. Telomere shortening limits the number of times cells can divide. When telomeres become critically short, cells undergo self-destruction or enter a dormant state.

The enzyme called telomerase is responsible for the maintenance of telomere length. However, the activity of telomerase virtually vanishes in most tissues after birth, remaining high only in germ cells (egg cells and spermatozoa) and stem cells.

Reactivation of telomerase, as shown in experiments with mice, may result in an increased life span, improved coordination, cognition, bone health, sugar metabolism, and aging-related blood indices.

Do genetics impact telomere length?

Several rare hereditary diseases such as dyskeratosis congenital or idiopathic pulmonary fibrosis are linked to mutations in genes involved in telomere maintenance. But even in the absence of inherited mutations, telomere length is highly determined by inheritance.

Although genetic mechanisms of telomere inheritance are not fully elucidated, the inheritance from the mother’s side seems stronger than that from the father’s side. Interestingly, telomeres of children born to older fathers tend to be longer because telomeres in spermatozoa keep prolonging with age.

The role telomeres play in lifespan and disease

Short telomeres and accelerated telomere shortening are associated with reduced overall lifespan and disease-free years of life. Also, scientists have linked short telomeres to numerous disorders that normally become more prevalent with age: cardiovascular diseases such as myocardial infarction or stroke, type 2 diabetes, Alzheimer’s disease, arthritis, osteoporosis, etc.

Cancer is also considered an age-related disease. Indeed, shorter telomeres have increased cancer risk. One study found that in people who developed cancer during the observation period, the annual telomere shortening rate was twice as high as in those who did not. Also, cancer often occurs at a young age in people with hereditary telomere diseases.

Cancer cells divide more frequently than healthy cells, therefore, their telomeres shorten more quickly. To prevent this process, telomerase is reactivated, allowing cancer cells to divide endlessly despite short telomeres.

Strategies to prevent telomere shortening

Telomere length depends both on inheritance and lifestyle. Lifestyle factors that can accelerate telomere shortening include:

• Smoking;
• Obesity;
• Unhealthy eating;
• Insufficient exercising;
• Environmental pollution;
• Stress.

For instance, research shows that daily smoking of one pack of cigarettes results in losing an additional 5 base pairs per year in women. The impact of obesity seems even more pronounced: the excessive loss of telomeres in obese people translates into losing 8.8 years of life.

A diet containing sufficient fiber and polyunsaturated fatty acids (as in the Mediterranean or Japanese diets) seems to prevent telomere shortening. Likewise, antioxidants, especially omega-3 fatty acids, are associated with a reduced rate of telomere shortening.

Higher levels of physical activity are associated with longer telomeres. Exercising increases telomere length by activating telomerase, enhancing muscle repair, and reducing inflammation and oxidative damage.

Lastly, stress hormones reduce the levels of antioxidant proteins, causing increased oxidative DNA damage and telomere shortening. Thus, measures to alleviate stress such as meditation or mindfulness may prevent these changes.

Measuring telomere length

Most laboratories use a blood sample to test telomere length in white blood cells. There are several different methods for telomere length testing. Some tests, such as Southern blotting and quantitative polymerase chain reaction, use isolated DNA. Other tests, such as quantitative fluorescence in situ hybridization (Q-FISH) or flow cytometry-based technique (flow-FISH), use intact cells. Most tests use probes that bind to the repeating DNA sequences and then employ different methods to measure the extent of binding.

While most tests measure average telomere length, scientists have developed more sophisticated tests to measure all individual telomeres, including the shortest ones. Two examples of such tests are:

• Single Telomere Length Analysis (STELA).
• Telomere Shortest Length Assay (TeSLA).

Commercial direct-consumer telomere tests using different methods are already available in the market.

Telomere testing: Is it worth doing?

Telomere length is considered to be a biomarker of aging, and scientists propose using it to predict age-related diseases and longevity. However, there are several things to take into account concerning telomere length testing:

1. The laboratory methods are diverse, not fully standardized, and cannot be directly compared. The actual telomere length and their shortening rate are important; therefore, scientists should perform the same serial measurements method.
2. Telomere shortening is a dynamic process and may accelerate by factors not associated with aging, such as activation of the immune system.
3. The association between telomere length and aging is not straightforward. Research has not established whether the shorter telomeres are the cause or the effect of aging.
4. Telomere length is not the only biomarker of aging.

Besides telomere testing researchers and scientists have proposed other biomarkers as indicators of biological age, including:

• Genomic instability.
• DNA methylation (“epigenetic clock”).
• Mitochondrial dysfunction.
• Impaired regulation of proteins within the cell.
• Skin and gut microbiome.

More studies are needed to establish the most robust ones.