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DNA telomere screen to determine cell biological age

If you feel old for your age in terms of physical looks or body function, your cells/DNA might be biologically aging faster relative to your chronological age.

Telomere screening to determine biological age

What is the purpose of screening my telomeres?

Telomere attrition (shortening) is one of the nine hallmarks of ageing, as well as being the driver of biological processes underlying each of the other hallmark of aging.

While it is normal for telomere length to decrease with age, it is not possible to determine the exact length or rate of telomere shortening via a physical examination. Telomere screening utilises quantitative polymerase chain reaction (qPCR) to analyse the average length of telomeres across all chromosomes to estimate the biological age of an individual.

Telomere screening can aid in:

  • Determining biological age and pace of aging
  • Estimating the risk of developing cancer and/or suffering from ailments associated with aging (such as stem cell exhaustion or hair loss)
  • Early detection and intervention if the patient is suspected to be suffering from telomere length related disorders (short telomere syndromes like pulmonary fibrosis)

Telomere length as a biomarker of healthy aging and longevity

Our DNA naturally decreases in length each time a cell replicates/divides.

Telomeres are located at the ends of our DNA strands and protect our genes from being deleted or damaged by acting as buffers that shorten in place of the coding portions of our chromosomes.

Telomere length determines how many times a cell can divide and therefore, its lifespan as cells can no longer divide when their telomeres reach critical length (become too short). The rate of telomere shortening varies between individuals; two individuals with the same chronological age can have differing rates of telomere degradation and thus, vastly different telomere lengths and biological ages.

Chronological age vs biological age – chronological age is the number of years you have lived (also referred to as your real age), while biological age is the age of your cells/DNA (based on the length of telomeres). Biological age is independent of chronological age, and an individual can be biologically older, younger or equal to their chronological age.

Cawthon’s study indicates that individuals with longer telomeres live five years longer than those with shorter telomeres on average, but individuals with longer telomeres are still affected by telomere shortening. The rate of aging can thus be affected by factors that affect the rate of telomere shortening.

Impact of telomere length and biological age on longevity

As we live and age, our cells are constantly replicating, making telomere length an indicator of our biological age and a biomarker of our cells’ health. Age related progressive shortening of the telomeres is associated with:

  • Cell apoptosis (cell death)
  • Cell senescence (cell inactivity/cessation of cell division)
  • Genome instability and potential cancer formation
  • Early onset of age-related diseases/conditions  

Additionally, an abnormally fast rate of telomere shortening or abnormally short telomere length relative to chronological age can be an indicator of disorders like:

  • Dyskeratosis congenita (a rare progressive congenital disorder)
  • Accelerated-aging syndromes/short telomere syndromes (such as pulmonary fibrosis)

Knowing your telomere length can help you verify if you are suffering from telomere dysfunction associated disorders or determine how susceptible you are to prematurely developing age-related conditions and help you adjust your lifestyle to slow down aging and improve your biological health.

If you are interested in reading more about the impact on telomere length on health, please continue reading until the end of this service page.

Telomere screening at the Clifford Clinic

Telomere screening utilises quantitative polymerase chain reaction (qPCR) to analyse the average length of telomeres across all chromosomes to estimate the biological age of an individual.

When you undergo a telomere screen at Clifford Clinic, you can expect:

  • A detailed genetic report indicating your estimated biological age and average telomer length.

 

  • A private consultation session with our doctor(s) to aid you in interpreting your report and understanding the significance of your results.

 

  • A detailed therapeutic report and personalised recommendations on what lifestyle changes and/or active compounds you should consume to reduce your rate of telomere degradation/biological aging based on the results of your genetic report.

Lifestyle and diet can affect your rate of biological aging

Oxidative stress is one of the main causes of DNA and telomere damage, antioxidants are thus linked to reduced rate of telomere shortening. A diet high in foods containing anti-inflammatory compounds and/or antioxidants like beta-carotene, vitamin E, vitamin C, and omega-3 fatty acid can preserve telomere length.

Changes to an individual’s lifestyle like increasing the frequency of exercise can help reduce the rate of biological aging. Exercise (like Zone 2 training) can reduced oxidative stress, improve the rate of elimination of metabolic waste, and lessen the amount of harmful fat in the body, which reduces the rate of biological aging by:

  • Increasing telomerase (an enzyme that elongates telomeres) activity
  • Increasing telomere stabilisation
  • Reducing telomere shortening

Recommendations will be made based on your genetic report to produce a comprehensive list of active ingredients that are tailored towards best helping you reduce your rate of biological aging and telomere shortening.

How is the DNA sample taken?

Before a sample is taken, our doctors and clinic staff will provide counselling to the patient with regards to the possible outcomes of the screen and the significance of the possible outcomes, explain the methodology used for the screen, assess the patient’s health, as well as address any questions the patient may have via a pre-screening consultation session.

After the pre-screening consultation:

  1. A DNA sample will then be collected from the patient via a painless mouth swab in the clinic.
  2. The clinic will send the DNA sample to the laboratory for analysis on the behalf of the patient.
  3. Once the telomere screen results are ready, the genetic report will be given to the patient and a post-screening consultation session will be arranged at the request of the patient.

What are telomeres?

Telomeres are regions of repetitive nucleotide sequences located at the terminal (end) regions of chromosomal DNA that act as “caps” covering the ends of the chromosomes, protecting the coding region of chromosomal DNA from progressive degradation as a result of cell/DNA replication by being degraded in place of the coding region. Telomere length naturally decreases as cells replicate and an individual ages, making it an indicator of biological age.

What determines and affects telomere length?

Genetics

Telomere length and age related telomere shortening is affected by both genetics and environmental factors. Genetic mutations can result in short telomeres and the development of the associated short telomere syndromes (pulmonary fibrosis and dyskeratosis congenita).

Parental reproductive cells – studies show that telomere lengths in parental reproductive cells (germ cells) are potentially heritable.

Oxidative stress

Oxidative stress-mediated DNA damage caused by oxidants/free radicals is one of the major causes of telomere shortening. Oxidative stress plays a role in the development of metabolic syndrome, which is in turn, associated with worsening oxidative stress faced by cells.

Metabolic syndrome: type 2 diabetes, cardiovascular diseases, obesity, hyperglycaemia, insulin resistance, arterial, and hypertension

Stress is another contributing factor to oxidative stress. The adrenal gland releases glucocorticoid hormones when an individual experiences high stress, glucocorticoid hormones increase oxidative damage to DNA and accelerated telomere shortening.

Research indicates that the difference in biological age based on telomere length between two groups of women studied, one group being consistently exposed to stress, was estimated to be around ten years.

Environmental and lifestyle factors

Consistent exposure to pollution such as traffic exhaust, cigarette smoke, or other air pollutants can negatively impact telomere length. A medical study conducted on the impacts of smoking on telomere length indicated that telomere length is loss at a rate of 25.7–27.7 base pairs per year if an individual smokes daily.

Telomeres’ role in DNA protection and preventing cancer

Genome instability caused by short telomeres or accelerated telomere shortening is associated with the development of cancer.

Telomeres are essential for protecting and maintaining the integrity of DNA (deoxyribonucleic acid). Each time a cell divides, the ends of the chromosomes are naturally shortened due to the end replication problem.

Without telomeres capping the ends of the chromosomes, vital genetic code (coding regions of DNA needed for normal cell function and life) located at the terminal regions might be loss/damaged as a result of DNA replication.

Protection against gene loss (the end replication problem)

A single strand of DNA has a 5′ end (five-prime end) and a 3′ end (three-prime end). Human DNA is made of two single strands of DNA wound around each other to form a double helix structure (double-stranded DNA structure).

Cells in the body are constantly replicating/dividing, with DNA replication playing an essential part in cell division. During cell division:

  1. A point called the origin of replication is formed on the double-stranded DNA; replication is initiated at this point once the double-stranded DNA is “unzipped”.
  2. Primers (short stretches of DNA) initiate replication by attaching to the DNA stand that is being duplicated (the template strand).
  3. DNA polymerase (an enzyme that synthesises DNA nucleotides) binds to the primer and uses the original strand as a template to synthesise the new stand.

DNA can only be synthesised in a 5′ to 3′ direction. Depending on the direction that the new strand is being synthesised relative to the origin of replication, either away or towards the origin, only a single primer might be needed (the leading strand) or multiple primers might be needed to synthesise the new strand in fragments (the lagging strand).

The unidirectional synthesis of DNA (5′ to 3′) results in a single-stranded overhang occurring naturally in the newly replicated DNA where the last primer of the lagging strand sat on the template strand.

As the template strand cannot be fully replicated due to the position of the last primer, every time a cell replicates an overhang is formed and loss, causing the DNA of the cell to become progressively shorter with each replication cycle; this is the end replication problem.

If telomeres are not present at the ends of the chromosomes, the overhang will form in the coding region of DNA, causing gene loss via the end replication problem.

Preventing gene corruption and DNA structural damage

The ends of chromosomes/DNA resemble double-stranded breaks. As double-stranded breaks are indicative of DNA structural damage; the DNA’s natural repair machinery may mistake the ends of the chromosomes as atypical breaks in the DNA sequence and attempt to “fix” the ends by:

  • Fusing the ends together and damaging genetic information.
  • Initiating cell apoptosis and killing the cell.

Additionally, the ends of uncapped chromosomes can fuse together without the aid of the cell’s DNA repair machinery. Abnormal chromosomal end-to-end fusion is very detrimental for health as end-to-end fusion can result in cancer development (such as breast cancer) or impairment of vital cell processes due to loss of genes or mutations in genes.

Systemic metabolic diseases

Gut microbiota is indicated to be involved in the development of metabolic diseases, such as type 2 diabetes and obesity, due to their role in metabolic regulation.

  • Type 2 diabetes – Butyrate is a short-chain fatty acid produced by certain gut microbes that is associated with decreasing insulin resistance. Gut flora compositions that are low in butyrate-producing microbes may thus increase the acquisition risk of Type 2 diabetes.
  • Obesity – Gut microbiome composition affects the amount of energy extracted from food, regulate energy absorption, fat storage, and central appetite. As microbiota facilitate the fermentation of indigestible carbohydrates, reduced diversity in microbiota composition leads to reduced metabolic energy consumption and thus, increased risk of obesity.

Telomere length is a driver of the hallmarks of aging

Progressive shortening of telomeres and the resulting decline in their function and structure are linked with aging. Accelerated telomere shortening leads to early onset of age-related diseases/conditions such as:

  • Hair loss (alopecia)
  • Stem cell exhaustion
  • Cardiovascular disease
  • Coronary disease
  • Osteoarthritis
  • Metabolic syndrome (Such as type 2 diabetes and obesity)
  • Cancer

Additionally, the nine hallmarks of aging are: Telomere attrition, genomic instability, epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication.

As mentioned above, telomere attrition is one of the nine hallmarks of ageing as well as an amplifier and driver of biological processes underlying each of the other hallmarks of aging. Genetics, negative life style choices, as well as improper nutrition can drive accelerate aging by acerating telomere shortening.

Telomere dysfunction associated disorders

Individuals born with are born with or have developed abnormally short telomeres can suffer from several disorders, also known as Telomere Biology Disorders (TBD).

Organs such as the skin, lungs, gastrointestinal tract (gut), and bone marrow that have higher cell turnover rates (high cell division rates) are typically the most affected by accelerated shortening of telomere lengths or abnormally short telomer lengths.

A telomere screen can be used as a tool to detect or check the risk telomere dysfunction associated disorders or help to confirm a diagnosis if the patient is suspected to suffer from a disorder linked to telomere dysfunction, allowing for early intervention when intervention possible. 

Pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a lung degenerative disease commonly associated with short telomere length. Symptoms of IPF are: shortness of breath, dry cough, fatigue, aching muscles and/or joint, and clubbing of the tips of the fingers/toes.

Dyskeratosis congenita

Dyskeratosis congenita is a disorder caused by mutations in the genes that help maintain telomere structure, resulting in short telomere length and improper telomere function. Symptoms include: poorly grown or abnormally shaped fingernails and toenails, abnormal “lacy” skin pigmentation, and formation of white patches in the interior of the mouth.

Chromosomal instability due to impaired telomere maintenance mechanisms associated with  dyskeratosis congenita may also result in the development of cancer.

Hematopoietic dysfunction

Bone marrow failure can result from dyskeratosis congenita or telomere dysfunction without dyskeratosis congenita. Symptoms of bone marrow failure can show from as early as birth to as late as late adulthood.