Cellular aging is linked to structural changes in the brain

Summary: Telomere lengthening resulted in structural changes in the brain, including cortical thickening. By contrast, telomere shortening is associated with gray matter reduction, specifically in the precuneus.

Source: Max Plank Institute

Telomeres are protective caps at the ends of chromosomes that become shorter with each cell division. If they become so short that the genes they protect could be damaged, the cell stops dividing and renewing. Consequently, the cell is increasingly unable to perform its functions. This mechanism is one of the ways in which we age.

Telomere length is therefore regarded as a marker for the biological age of a person — in contrast to their chronological age. For two people of the same chronological age, the person with shorter telomeres has an increased risk of developing age-related diseases such as Alzheimer’s or cancer, and even a shorter life expectancy.

Telomere lengthening

One key to staying younger longer therefore seems to be related to the question: How do we slow down, stop, or even reverse the shortening of telomeres? Genetics and unhealthy lifestyle are important contributors to telomere shortening, along with psychological stress. Based on this knowledge, researchers have examined how much lifestyle can influence telomere length. Recent studies suggest that telomeres can change faster than previously thought, possibly taking just one to six months of mental or physical training to elongate. The exciting premise is that telomere lengthening may represent a reversal of biological aging processes. However, it remains unclear if telomere elongation actually reflects any improvement in a person’s overall health and aging trajectory.

“To explore whether a short-term change in telomere length, after only a few months, might actually be associated with changes in a person’s biological age, we linked it to another biomarker of aging and health: brain structure,” explains Lara Puhlmann, now a member of the Research Group ‘Social Stress and Family Health’ led by Veronika Engert at the Leipzig Max Planck Institute. The project had been initiated by Tania Singer as part of the ReSource Project.

Participants of the researchers’ study underwent four MRI examinations, each spaced three months apart, and provided blood samples on the same dates. Using the DNA of leukocytes from the blood, the scientists were able to determine telomere length using a polymerase chain reaction. The MRI scans were used to calculate the thickness of the cerebral cortex of each participant. This outer layer of grey matter becomes thinner with age. It is also known that some neurological and age-related diseases are associated with faster cortical thinning in certain brain regions.

Fast changes in biological aging

The result: “Across systems, our biological aging appears to change more quickly than we thought. Indices of aging can vary together significantly in just three months,” says Puhlmann. If the telomeres changed in length, this was associated with structural changes in the brain. In a period when participants’ telomeres lengthened during the study, it was also more likely that their cortex had thickened at the same time. On the other hand, telomere shortening was associated with reductions of grey matter. This association occurred specifically in a brain region called the precuneus, which is a central metabolic and connectional hub.

This shows a drawing of a telomere and brain
To determine the role of telomer length on brain structure scientists measured their length with the DNA of leukocytes from the blood using a polymerase chain reaction. Additionally, they calculated the thickness of the cerebral cortex with MRI scans of study participants. The image is credited to Max Plank Institute.

The above results suggest that even short-term changes in telomere length over just three months might reflect general fluctuations in the body’s health- and aging status. Many other questions, however, remain open. “We do not know, for example, which biological mechanism underlies the short-term changes in telomere length”, explains the scientist, “or whether the short-term changes really have a longer-term effect on health.”

Mental training

At the same time, the team of researchers investigated whether telomere length could be altered by nine months of mindfulness- and empathy-based mental training, and whether such systematic change in telomere length would also be reflected in cortical thickening or thinning. Previous data from the ReSource Project, which was supported by the European Research Council (ERC), had already shown that certain regions of the cortex can be thickened by training, depending on the respective mental training contents of three distinct modules, each lasting for three months. The physiological stress response could also be reduced by mental training with social aspects.

In contrast to their earlier work and previous findings from other groups, the team did not find any training effects on telomeres. Future studies will need to continue to address the question of which measures or behaviors most effectively stop or even reverse telomere shortening, and the biological aging process.

About this neuroscience research article

Source:
Max Plank Institute
Media Contacts:
Lara Puhlmann – Max Plank Institute
Image Source:
The image is credited to Max Plank Institute.

Original Research: Open access
“Association of Short-term Change in Leukocyte Telomere Length With Cortical Thickness and Outcomes of Mental Training Among Healthy Adults: A Randomized Clinical Trial”. Lara Puhlmann et al.
JAMA Network Open doi:10.1001/jamanetworkopen.2019.9687.

Abstract

Association of Short-term Change in Leukocyte Telomere Length With Cortical Thickness and Outcomes of Mental Training Among Healthy Adults: A Randomized Clinical Trial

Importance
Telomere length is associated with the development of age-related diseases and structural differences in multiple brain regions. It remains unclear, however, whether change in telomere length is linked to brain structure change, and to what extent telomere length can be influenced through mental training.

Objectives
To assess the dynamic associations between leukocyte telomere length (LTL) and cortical thickness (CT), and to determine whether LTL is affected by a longitudinal contemplative mental training intervention.

Design, Setting, and Participants
An open-label efficacy trial of three 3-month mental training modules with healthy, meditation-naive adults was conducted. Data on LTL and CT were collected 4 times over 9 months between April 22, 2013, and March 31, 2015, as part of the ReSource Project. Data analysis was performed between September 23, 2016, and June 21, 2019. Of 1582 eligible individuals, 943 declined to participate; 362 were randomly selected for participation and assigned to training or retest control cohorts, with demographic characteristics matched. The retest control cohorts underwent all testing but no training. Intention-to-treat analysis was performed.

Interventions
Training cohort participants completed 3 modules cultivating interoception and attention (Presence), compassion (Affect), or perspective taking (Perspective).

Main Outcomes and Measures
Change in LTL and CT.

Results
Of the 362 individuals randomized, 30 participants dropped out before study initiation (initial sample, 332). Data were available for analysis of the training intervention in 298 participants (n = 222 training; n = 76 retest control) (175 women [58.7%]; mean [SD] age, 40.5 [9.3] years). The training modules had no effect on LTL. In 699 observations from all 298 participants, mean estimated changes in the relative ratios of telomere repeat copy number to single-copy gene (T/S) were for no training, 0.004 (95% CI, −0.010 to 0.018); Presence, −0.007 (95% CI, −0.025 to 0.011); Affect, −0.005 (95% CI, −0.019 to 0.010); and Perspective, −0.001 (95% CI, −0.017 to 0.016). Cortical thickness change data were analyzed in 167 observations from 67 retest control participants (37 women [55.2%], mean [SD] age, 39.6 [9.0] years). In this retest control cohort subsample, naturally occurring LTL change was related to CT change in the left precuneus extending to the posterior cingulate cortex (mean t161 = 3.22; P < .001; r = 0.246). At the individual participant level, leukocyte telomere shortening as well as lengthening were observed. Leukocyte telomere shortening was related to cortical thinning (t77 = 2.38; P = .01; r = 0.262), and leukocyte telomere lengthening was related to cortical thickening (t77 = 2.42; P = .009; r = 0.266). All analyses controlled for age, sex, and body mass index.

Conclusions and Relevance
The findings of this trial indicate an association between short-term change in LTL and concomitant change in plasticity of the left precuneus extending to the posterior cingulate cortex. This result contributes to the evidence that LTL changes more dynamically on the individual level than previously thought. Further studies are needed to determine potential long-term implications of such change in relation to cellular aging and the development of neurodegenerative disorders. No effect of contemplative mental training was noted in what may be, to date, the longest intervention with healthy adults.

Trial Registration
ClinicalTrials.gov identifier: NCT01833104

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