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January 15th 2014

Here is an informative lecture series by Nobel Prize winner Elizabeth Blackburn on telomeres, telomerase, and stress:

 

October 26th 2013

Telomeres: Markers of Chronic Diseases

Telomeres are long hexameric (TTAGGG)n repeats located at the ends of linear eukaryotic chromosomes which interact with an assortment of DNA binding proteins to form the protective telosome complex. The average telomere length at birth in humans is approximately 10-12 kilobases; however, there is substantial variability in length between individuals, gender, ages, and ethnicities [3] . Telomeres truncate by approximately 30-100 bp after each mitotic division due to limitations in lagging strand DNA synthesis at chromosomal ends. As a result, telomeres are analogous to a “molecular clock” that reflects the number of past cell divisions. Furthermore, telomeric repeats maintain genomic stability by acting as a vanguard against nucleolytic decay, end-to-end chromosomal fusion, and subsequent atypical recombination [4]. Therefore, telomere length may also reflect the accumulation of past instances of environmental and biochemical trauma to the genome. In germline tissue and omnipotent stem cells, telomere shortening is overcome by expression of a ribonucleoprotein enzyme known as telomerase [4]. Telomerase is composed of two structural subunits; hTERC which is the embedded RNA template component, and the reverse transcriptase hTERT, which is responsible for extending telomeric repeats. Despite maintaining telomere length in germ cells, telomerase is only basally expressed in somatic tissue, resulting in unrestricted erosion of telomeres.

 

There are relatively few published studies investigating environmental and lifestyle correlates of telomere length. Smoking has been found to be the most prominent environmental correlate thus far; having been shown to be inversely associated with telomere length in numerous epidemiological studies [5-7] .  Valdes et al. found that age-adjusted telomere length was about 5 base-pairs per pack-year shorter, with 40 pack-years of smoking corresponding to 7.4 years of age-related erosion in telomere length.  The association may be due to deleterious components of cigarette smoke which may cause oxidative stress on white blood cells and their hematopoietic progenitors.

Aside from smoking, physical activity level has also been shown to be associated with telomere length. In the Nurse’s Health Study, Du et al. found that moderately and highly active women had marginally longer leukocyte telomere length compared with those who were least active [8]. Body Mass Index (BMI), a time-varying affecter and mediator of physical activity, has also been found to be associated with telomere length in the Nurse’s Health Study [8]. Concordantly, Valdes et al. also observed a weak inverse correlation of BMI with telomere length and a slightly stronger correlation with serum leptin, a marker of body fat [5].

Occupational factors such as work shift, exhaustion and sleep patterns have recently been investigated as correlates of telomere length. In the Nurses’ Health Study, Liang et al. found that women who slept less than 6 hours per night, had slightly lower telomere length compared to those with more than 9 hours of sleep in women under age of 50 [9]. Additionally, Parks et al. reported that compared to unemployed women with moderate or substantial work histories, those currently working full-time had shorter telomeres with an age-adjusted difference of -329bp (95%CI:-110 to -548) [10] . The authors also reported that longer-duration full-time work was also associated with shorter telomere length. In the Finnish Health 2000 Study, Ahola et al. found that after adjustment for age, sex, BMI, smoking, and socioeconomic status, individuals with severe exhaustion had significantly shorter leukocyte telomeres than those with no exhaustion; suggesting  that work related exhaustion is related to the acceleration of the rate of biological aging [11].

 

 

 


Immaculata De Vivo is an Associate Professor of Medicine and Epidemiology at the Harvard Medical School and Harvard School of Public Health. Dr. De Vivo oversees a laboratory that primarily focuses on the discovery and characterization of genetic biological markers that may modify disease susceptibility in human populations. Biological markers of interest include single nucleotide polymorphisms (SNPs), telomere length, and gene copy number variations (CNVs). Additionally, Dr. De Vivo is the director of the Dana Farber-Harvard Cancer Center High-Throughput Genotyping Core Facility.

Harvard School of Public Health

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Bldg 2 Rm 247

Boston, MA 02115

 

devivo@channing.harvard.edu

 

office: 617.525.2094

laboratory: 617.432.1642


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