The shortening of telomeres (red) are a natural ageing process, which can be influenced by genetic, lifestyle and environmental factors. — Wikimedia Commons
Similar to the plastic tips on shoelaces, telomeres are the protective caps at the ends of chromosomes, which maintain cellular health and genomic stability.
Comprised of repetitive DNA (dexoyribonucleic acid) sequences, they shorten each time the cell divides.
This shortening leads to cellular senescence (ageing), genomic instability and inflammation.
Thus, telomere length indicates biological ageing.
The build-up of senescent cells in the body is linked to the risk of chronic diseases like cardiovascular (heart) issues, diabetes, cancer and neurodegenerative conditions.
While genetics and gender affect telomere length, lifestyle choices significantly impact it.
Healthy habits such as having a nutrient-rich diet, exercising, good stress management and avoiding smoking, can slow telomere shortening.
Conversely, pollution and chronic stress can hasten it.
The disease link
Telomere dysfunction is linked to many age-related health conditions.
Telomeres have a complex role in cancer.
Critically-short telomeres can lead to chromosomal fusions, driving the transformation of normal cells into cancer cells, i.e. oncogenesis.
Most cancer cells are able to reactivate their telomerases, allowing them to avoid senescence and proliferate indefinitely.
Targeting telomerases can reduce tumour growth, but inhibiting it in just cancer cells (and not normal cells as well) remains a challenge.
Shortened telomeres are associated with cardiovascular conditions such as atherosclerosis and heart failure, as well as cerebrovascular conditions like stroke.
The shortening and loss of telomeres in vascular cells contributes to ageing, impaired repair and increased inflammation, worsening cardiovascular conditions.
Telomere shortening is linked to neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease.
In neurons (nerve cells), shortened telomeres hinder stress response and repair, accelerating disease progression.
A study showed that a decline in the telomere length of leucocytes (white blood cells) after the age of 70, correlates with higher dementia risk.
Shorter leucocyte telomeres are also linked to a 14% higher risk of depression after the age of 60, influenced by chronic inflammation and oxidative stress.
Shortened telomeres in T-lymphocytes (a type of white blood cell) hinder immune responses, thus increasing infection susceptibility and diminishing vaccine efficacy in older adults.
Telomere shortening affects bone health by impairing mesenchymal stem cell differentiation into osteoblasts, leading to osteoporosis, especially in post-menopausal women.
Influencing factors
Both genetic and environmental factors affect telomere length.
Genetics set the baseline, while lifestyle and environmental exposure influences the rate of shortening.
In general, chronic inflammation and oxidative stress drive telomere attrition.
Telomere shortening is both a cause and effect of chronic systemic inflammation.
Critically-short telomeres activate a DNA damage response, increasing pro-inflammatory cytokines and creating a feedback loop that accelerates telomere loss and cellular ageing.
Individuals with shorter telomeres show elevated levels of inflammation biomarkers like C-reactive protein (CRP) and interleukin-6 (IL6).
Research has also revealed a connection between telomere shortening and mitochondrial dysfunction, which negatively affects cellular energy metabolism.
Shortened telomeres hinder mitochondrial gene expression, thus reducing energy production and raising oxidative stress, which may lead to metabolic disorders like type 2 diabetes and obesity.
Inflammation also increases the production of reactive oxygen species (ROS), which can damage telomeric DNA.
Specific lifestyle factors that affect telomere length include:
Chronic psychological stress accelerates telomere shortening by activating the hypothalamic-pituitary-adrenal (HPA) axis and increasing cortisol levels, which lead to oxidative stress and inflammation.
Prolonged stress, such as that experienced while caregiving, results in telomeres that are biologically older.
Poor sleep quality and insufficient sleep contribute to shorter telomeres.
Insufficient sleep raises inflammation and oxidative stress, with studies showing that individuals sleeping less than five hours have significantly shorter telomeres compared to those sleeping seven to eight hours.
Diets rich in antioxidants, like the Mediterranean diet, correlate with longer telomeres.
Conversely, diets high in processed foods and sugars accelerate telomere shortening.
Moderate caloric restriction may help preserve telomere length.
Excessive alcohol intake is also a risk factor for telomere shortening due to oxidative stress and inflammation.
Studies show that heavy drinkers have significantly shorter telomeres compared to moderate consumers.
Regular physical activity is associated with longer telomeres.
Exercise reduces oxidative stress and may increase telomerase activity, promoting telomere maintenance.
Individuals with active lifestyles have longer telomeres than sedentary individuals.
Exposure to pollutants like air pollution and heavy metals accelerates telomere shortening through oxidative damage.
Individuals in polluted areas have shorter telomeres, emphasising the impact of environmental factors.
Socioeconomic status (SES) affects telomere length, with lower SES linked to shorter telomeres due to chronic stress, poor nutrition and limited healthcare access.
Studies show individuals in the lowest SES quartile have telomeres approximately 7% shorter than those in the highest quartile.
Childhood adversity also impacts telomere dynamics.
Possible interventions
Healthy lifestyle choices can slow telomere shortening.
A 2024 study links regular physical activity, a Mediterra-nean diet and adequate sleep to longer telomeres, while smoking, chronic stress and a poor diet hasten telomere attrition.
Recent findings emphasise that ideal cardiovascular health correlates with longer telomeres, and a moderately high-protein diet may help preserve telomere length in obese individuals.
Research in telomere biology has also led to potential therapies that may be able to counteract telomere shortening.
These include:
Telomerase is an enzyme that adds DNA to telomeres, thus helping to keep them long.
Compounds like cycloastragenol may act as telomerase activators, thus, extending telomere length and enhancing cellular function.
However, their long-term safety and effectiveness in humans are still being studied.
Telomerase is active in germ and certain stem cells, but mostly inactive in somatic cells, which make up most of our body.
Reactivating it in somatic cells through an activator may have anti-ageing potential, but may also risk promoting cancer.
Antioxidants like vitamin C, vitamin E and omega-3 fatty acids reduce oxidative stress and inflammation, thus slowing telomere shortening.
CRISPR-Cas9 and similar technologies may be able to target telomerase activity in cancer cells and repair dysfunctional telomeres, thus representing a potential breakthrough in telomere therapies.
Tankyrase is an enzyme that regulates a number of cellular processes, including telomere maintenance.
Tankyrase inhibitors aim to stabilise telomeres and may have applications in cancer treatment and anti-ageing.
Future research
Despite advancements, many questions still remain about telomere biology, including their relationship with the immune system and tumour microenvironment.
Understanding telomere health could be crucial for enhancing longevity and quality of life.
Current knowledge on telomere length suggests that it can serve as a biomarker for disease risk and guide personalised interventions.
However, standardisation of measurement techniques and establishing causality are ongoing challenges.
Continued research on telomere health is vital for combating age-related diseases and enhancing quality of life.
Future research should prioritise structural studies, biomarkers for dysfunction and personalised therapies.
In the future, integrating telomere length assessments into routine health checks could improve early detection and preventive strategies for age-related diseases.
Datuk Dr Nor Ashikin Mokhtar is a consultant obstetrician and gynaecologist, and a functional medicine practitioner. For further information, email starhealth@thestar.com.my. The information provided is for educational and communication purposes only, and it should not be construed as personal medical advice. Information published in this article is not intended to replace, supplant or augment a consultation with a health professional regarding the reader’s own medical care. The Star does not give any warranty on accuracy, completeness, functionality, usefulness or other assurances as to the content appearing in this column. The Star disclaims all responsibility for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such information.
