- Telomeres are regions at the end of chromosomes that protect against DNA damage.
- Telomeres get shorter with every division that a cell undergoes, and the shortening of telomeres is associated with biological aging and age-related conditions such as Alzheimer’s disease.
- A new large study found that shorter telomere length in white blood cells was associated with a greater increase in markers of brain degeneration measured using MRI.
- Shorter telomere length was also associated with a higher risk of dementia, suggesting that longer telomere length could protect against dementia.
Previous studies suggest that shorter telomere length is associated with biological aging of the brain and a greater risk of neurodegenerative conditions. A recent study published in
Changes in these markers of brain structure and function precede clinical symptoms of dementia, and these findings suggest that the association between telomere length and dementia risk may be mediated through these changes in brain structure.
“This is the largest and most in-depth study of telomere length (a marker of biological aging) and brain structure/function. We found links between longer telomeres and larger volumes of the brain (such as the hippocampus) that are affected by dementia. These may explain why/how longer telomeres are protective against dementia.”
— Dr. Anya Topiwala, of Oxford Population Health, part of the University of Oxford, UK, and lead study author
Each of the chromosomes present in the cell nucleus consists of a double-stranded molecule of DNA. The end of each chromosome consists of telomeres, a region made up of repeats of a short DNA sequence (TTAGGG).
These short repeated DNA sequences in the telomere are covered by shelterin proteins. The telomer-shelterin complexes help protect the ends of the chromosome from being damaged and avert the fusion of one chromosome with another.
Moreover, the ends of the chromosome resemble breaks in the DNA and can be recognized as broken by DNA repair enzymes. This can, in turn, activate pathways involved in senescence, which is the irreversible arrest of cell division. Senescence is one of the mechanisms that contribute to biological aging.
The telomere-shelterin complex prevents the recognition of the chromosome ends as being broken.
Each of the two DNA strands of the chromosome is duplicated during cell division, and this process is carried out by an enzyme called DNA polymerase. The DNA polymerase binds to a short fragment of RNA called primer to initiate DNA synthesis.
The process of DNA replication occurs at multiple sites along the same strand, and the gap left behind between newly created DNA fragments after the removal of the RNA primer is filled in by DNA polymerase.
However, DNA polymerase cannot fill the gap left at the end of the chromosome after the removal of the RNA primer. Thus, the telomeres start to get increasingly shorter with each cell division and, consequently, with aging.
“Dementia impacts more than 45 million people worldwide. Because shorter chromosomal telomeres are a sign of aging and related to both neurodegeneration and incidence of dementia, it is plausible that interventions targeting telomere length preservation could one day aid in preventing or delaying Alzheimer’s disease and related dementias.”
— Dr. Jennifer Bramen, senior research scientist at the Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, California, speaking to Medical News Today
The shortening of telomeres can result in the cells undergoing senescence and, thus, biological aging. In addition, studies suggest that the decrease in telomere length is also associated with an increased risk of neurodegenerative conditions such as Alzheimer’s disease (AD).
Individuals with Alzheimer’s disease show changes in brain structure before the manifestation of clinical symptoms. Specifically, individuals with Alzheimer’s disease show changes in both the
The gray matter is composed of neuronal cells and is involved in the processing of information. Alzheimer’s disease is characterized by a decline in gray matter volume throughout the brain, including in the hippocampus, a brain region involved in memory. Disruption to neuronal networks within the gray matter
In contrast, white matter consists of neuronal processes involved in the transmission of information. Studies have shown that individuals who show reduced integrity of white matter tracts are at an increased
However, the association between telomere length and these markers of brain degeneration has not been extensively examined.
In the present study, the researchers used MRI scans to examine the association between telomere length and changes in brain structure. The study consisted of MRI data from 31,661 individuals participating in the UK Biobank, a database that contains biomedical data from over a half million U.K. residents.
The researchers used blood samples obtained at baseline from these participants to isolate DNA from leukocytes, also known as white blood cells, and assess telomere length. The cognitive function of the individuals was assessed at baseline and then about 5.8 years later via an online survey.
The researchers found that longer leukocyte telomere length was associated with a larger volume of gray matter across the entire brain. Longer telomere length was also associated with greater volume in several brain regions, such as the hippocampus, associated with executive functions.
In addition, individuals with longer leukocyte telomeres length were also more likely to show greater integrity of white matter fiber tracts and fewer signs of lesions. Specifically, longer telomere length in leukocytes was associated with greater integrity of the corpus callosum, the white matter tract that conducts information between the two brain hemispheres, and major association fiber tracts that conduct impulses within the same hemisphere.
MRI measurements showing the contrast between the signal intensity of gray matter and white matter can be used as a marker of neurodegeneration associated with Alzheimer’s disease. A decrease in the contrast has been linked to increasing disease severity.
Consistent with this, the present study found that longer leukocyte telomere length was associated with lower contrast between grey and white matter in brain regions involved in processing sensory information.
Lastly, there was a negative correlation between longer leukocyte telomere length and the risk of developing dementia. Such an association was not observed between leukocyte telomere length and the risk of stroke or Parkinson’s disease.
Although these results suggest that longer telomere length may be associated with a lower risk of dementia and reduced brain degeneration, the researchers cautioned that these results are based on analysis of telomere length in white blood cells rather than brain tissue.
“For this study, there are some limitations to keep in mind. Telomere length was measured in blood, not the brain (not possible in living humans!), and it is not yet clear how closely the two align. Also, the UK Biobank sample is healthier than the general population,” noted Dr. Topiwala.
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