Studies have increasingly established that progressive loss of telomemeric repeats leads to cell senescence and death, closely correlated with organismal aging in model organisms and humans with telomerase deficiency.
Researchers have discovered that certain lifestyle behaviors can help to strengthen and stabilize telomeres for healthy cell function. These include healthy diet, adequate sleep and taking measures to alleviate chronic stress.
At the very ends of chromosomes lie stretches of DNA known as telomeres, which function much like the plastic tips on shoelaces, preventing chromosome ends from fraying or sticking to each other. With each cell division, telomere length shortens, which is a normal part of cellular aging. This shortening is one of the reasons why cells eventually lose their ability to divide and either die or enter a state called senescence.
Lifespan
Telomere shortening directly correlates to cell aging. Human cells with rapidly dividing divisions see their telomeres become gradually shorter with each division until reaching a threshold length that leads to either senescence or apoptosis and therefore cell death.
Human cells’ progressive telomere shortening leads to loss of functional proteins, increased genetic damage and cell degeneration, as well as eventual age-related diseases and mortality.
Lifestyle factors have been shown to impact the rate at which telomeres shorten, which in turn may have detrimental effects on health and longevity. Telomerase acts to counteract shortening by actively maintaining high levels of activity – thus delaying cell senescence and disease progression.
Individuals carrying mutations of the telomerase gene (e.g., Dyskeratosis Congenita syndrome) or having an insufficient telomere elongation factor deficiency experience premature cellular senescence at an increased risk for atherosclerosis, cardiovascular disease, neurological diseases and cancer.
Cancer
Human cell telomeres shorten with each division until reaching a threshold length that initiates cell senescence or apoptosis. Telomere shortening can be tracked in real time using quantitative PCR (qPCR). This technique measures frequency of strand break events.
Telomeric DNA, in contrast to coding DNA, is more susceptible to damage because it lacks protective sequences like stop codons. Therefore, damage repair rates tend to be slower when dealing with telomeric damage compared with other forms of genome-wide DNA damage.
Telomere shortening can be partially mitigated through expression of the enzyme telomerase, which adds small stretches of telomeric DNA at each cell cycle. Unfortunately, evidence has suggested that dysfunctional telomeres may contribute to age-related diseases; consequently, study of telomere biology has become an integral component of research on human health and disease.
Cardiovascular Disease
Humans and most vertebrates experience their telomeres becoming shorter with each cell division, so each gene encoded provides an enzyme called telomerase to restore them by adding small pieces of DNA at the ends of each chromosome.
Over time, however, telomeres become so short that they initiate a process known as senescence or DDR (DNA damage response). This impairs stem cells’ ability to divide, leading to further dysfunctions which ultimately contribute to cell aging and organismal senescence.
Studies suggest that many factors affect telomere length, including mental health, chronic stress and physical activity. One study revealed that psychological distress was linked with decreased leucocyte telomerase activity and shorter telomeres among chronic heart failure patients; another demonstrated that people who smoke have shorter telomeres than non-smokers; this finding may contribute to the occurrence of diseases related to smoking such as emphysema, intestinal disorders or even liver cirrhosis.
However, the picture is complex, as not all individuals with shorter telomeres will develop disease, nor will all individuals with longer telomeres escape it. Genetics, environment, and chance play roles just as significant, indicating that telomere biology is one piece of a multifaceted puzzle. Still, understanding this piece deepens our grasp of human biology and its vulnerabilities.
Neurodegenerative Diseases
Proliferating cells’ telomeres become shorter with each cell division. After a certain number of cell divisions, however, their critical shortening triggers apoptosis or cellular senescence – known as Hayflick limit.
Contrary to proliferating cells, non-proliferating ones like heart muscle have longer telomeres as their cells are continually replaced with new ones. Unfortunately, cardiovascular disease (CVD) in humans is associated with leucocyte telomere shortening and the accumulation of dysfunctional ones, shortening these telomeres even further and increasing cardiovascular risks.
One groundbreaking clinical study demonstrated that leucocyte telomere length in patients with severe coronary artery disease was significantly shorter than in age-matched controls, equivalent to 8.6 years of aging. Subsequent research confirmed this correlation and also demonstrated increased levels of cellular senescence markers and TAFs among those diagnosed with coronary artery disease110,111.
Telomere shortening can be caused by factors like oxidative stress, inflammation and senescence; lifestyle interventions like dieting restrictions, exercise programs and using ACE inhibitors for high blood pressure treatment can reduce this oxidative stress to slow telomere shortening.
