The last century has been characterized by an unprecedented increase in human life expectancy almost everywhere in the world.
This demographic trend, however, has not been accompanied by the same extension in useful life and productivity, we are talking about quality of life.
Today, telomere length remains one of the most widely used biomarkers of aging in epidemiological and clinical studies.
In recent years, this marker is also being increasingly used as a potential disruptor in personalized medicine.

In today’s article we will dive a little into the topic of aging, telomeres and how simple but powerful actions can help us live longer and better.

What are telomeres?

Telomeres are complexes consisting of tandem repeat DNA (sequential repeats are from TTAGGG) combined with associated proteins that play a key role in protecting chromosome ends and maintaining genome stability.
These repeats prevent chromosomes from fusing together and DNA repair proteins from recognizing them as a double-strand break.

Telomeres shorten in parallel with aging

They are considered a biological clock, as they shorten in parallel with aging.
In addition, short telomeres are associated with several age-related diseases.
However, the variability in telomere shortening independent of chronological age suggests that it is a modifiable factor.
In fact, it is regulated, among other things, by genetic damage, cell division, aging, oxidative stress, and inflammation, among other factors.

One of the causes is that DNA polymerase incompletely replicates linear chromosomes, and that is why telomeric DNA shortens with repeated cell divisions until telomeres reach a critical length, at which point the cells enter senescence. That is why telomere length is an indicator of biological aging, and telomere dysfunction is related to age-related pathologies, such as cardiovascular diseases, Parkinson’s, Alzheimer’s and cancer.

Why are they shortened?

During the replication of linear chromosomes (these are found in most eukaryotic cells), the enzyme DNA polymerase replicates the ends of the DNA in a 5′ to 3′ direction using an RNA primer for initiation.
When this RNA primer is removed after DNA replication, the telomeric DNA sequence is lost from the ends.
For this reason, in each cycle of somatic cell division, telomeres are shortened by 50 to 200 base pairs through incomplete synthesis of the lagging strand during DNA replication.
This is due to the inability of DNA polymerase to fully replicate the 3′ end of the DNA strand, a phenomenon commonly referred to as “the final replication problem.” https://doi.org/10.1038/newbio239197a0

Telomere length is epigenetically regulated by DNA methylation and histones.
When inflammation occurs and the accompanying proliferation of cells – especially during infections – it results in the loss of telomere repeats due to increased cell division.
Thus, the plasma concentration of the inflammatory marker C-reactive protein is negatively correlated with telomere length. https://doi.org/10.1210/jc.2005-1814

In germ cells, stem cells, and many cancer cells, the enzyme telomerase reverse transcriptase adds a telomeric sequence to the ends of the newly synthesized DNA, maintaining telomere length.
When cells are not dividing and DNA is not replicating, the protein complex associated with telomere repeats called the refuge prevents unwanted telomere lengthening by restricting access to telomerase.
DOI: 10.1101/gad.1346005

Inflammation produces oxidative stress

In addition, inflammation also produces oxidative stress.
When this oxidative stress is low-level, it can cause oxidative base modifications and single-strand breaks in DNA.
This type of damage accumulates in telomeres since the G-rich telomeric sequence is more sensitive to oxidative damage.
DOI: https://doi.org/10.1074/jbc.274.2.962

The loss of protective telomere function due to the wear and tear of repeats makes chromosomes susceptible to fusing with other chromosomal ends and double-strand breaks, resulting in chromosomal rearrangements that affect genomic stability.
Critically short telomeres lose their epigenetic marks and are prone to recombinations.
DOI: https://doi.org/10.1038/ng1952

Telomere dysfunction is related to the development of age-related pathologies, as mentioned above, such as Parkinson’s disease, Alzheimer’s disease, cardiovascular diseases and cancer.

What solutions are proposed?

Telomere length has been shown to be associated with nutritional status in human and animal studies.
Healthy lifestyles and diets are positively correlated with telomere length.
Changes in diet and lifestyle can modulate telomerase activity in peripheral blood mononuclear cells, although it is unclear whether this translates into changes in telomere length.

TA-65

The root of Astragalus membranaceus is able to increase the average length of telomeres and decrease the percentage of critically short telomeres and DNA damage.
Restoring telomerase activity in the mice studied, by reintroducing one copy of the Terc gene, rescues critically short telomeres and reverses chromosomal instability and cell and tissue defects associated with telomerase deficiency, including stem cell rescue, dysfunction and lifespan of the organism.

The use of TA-65 results in telomerase-dependent short telomere elongation and rescue of associated DNA damage, demonstrating that TA-65’s mechanism of action is through the telomerase pathway.
DOI: 10.1111/j.1474-9726.2011.00700.x

The findings also suggested that therapies aimed at reactivating telomerase and lengthening short telomeres with age could have significant anti-aging effects.
In this sense, it has recently been shown that the enhanced activity of telomerase in mice that overexpress telomerase reverse transcriptase (TERT), is capable of delaying aging and prolonging the half-life by 40%, in addition to greater resistance to cancer.

Thus, TERT overexpression improves the fitness of epithelial barriers, particularly the skin and gut, and produces a systemic delay in aging accompanied by an extension of median lifespan.
DOI: https://doi.org/10.1016/j.cell.2008.09.034

Vitamin D3

The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3, possesses immunosuppressive properties.
This is reflected in the inverse relationship between plasma vitamin D concentration and the inflammatory marker C-reactive protein. https://doi.org/10.1210/jc.2005-1814

Telomere length is negatively correlated with plasma concentration of C-reactive protein.
The addition of 1α,25 dihydroxyvitamin D3 to the cell culture medium reduces the expression of the proliferation factor granulocyte and macrocyte colony-stimulating factor that is important for the proliferation of all hematopoietic cell lineages and thus reduces lymphocyte proliferation.
In addition, vitamin D also reduces the expression of the inflammation mediators interleukin-2 and interferon gamma. https://doi.org/10.1073/pnas.84.10.3385

Omega-3

Plasma concentration of marine omega-3 fatty acids, decosahexaenoic acid and eicosapentaenoic acid, has been shown to be positively associated with a decrease in telomere length in study subjects over a period of 5 to 8 years.
DOI: 10.1001/jama.2009.2008

People who had a higher initial concentration of omega-3 fatty acids showed the maximal effect of omega-3 fatty acids on telomere wasting.
The concentration of omega-3 fatty acids in plasma is associated with low pro-inflammatory markers and high anti-inflammatory markers.

In mice, the diet enriched in marine omega-3 fatty acids improved the activities of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase and increased lifespan. https://doi.org/10.1093/jn/131.10.2753

Changes in anti-inflammatory and antioxidant properties induced by omega-3 fatty acids decrease cell turnover and oxidative DNA damage and may therefore reduce telomere shortening.

That is why from Salengei we do not hesitate to recommend MorEPA® Platinum, whose pearls contain 1100 mg of omega-3, of which 764 mg are EPA and 236 mg of DHA.
In addition, these pearls contain vitamin D3, which generates a synergistic action, enhancing the benefits.

Conclusion

Fortunately, science today allows us to measure, predict in a certain way and prevent aging.
Telomere length is proof of this and there is still much to be done to improve, but we also believe that the implementation of healthy routines and the incorporation of specific food supplements will help us live a fuller life with fewer diseases.

Because at Salengei we believe that ageing is just that, right, living a longer, quality life.

As you know, aging is one of our favorite topics and that is why we dedicate a lot of effort, hours of research and we are pleased to share the news with you.