Telomeres and Immunological Diseases of Aging

Abstract

A defining feature of the eukaryotic genome is the presence of linear chromosomes. This arrangement, however, poses several challenges with regard to chromosomal replication and maintenance. To prevent the loss of coding sequences and to suppress gross chromosomal rearrangements, linear chromosomes are capped by repetitive nucleoprotein structures, called telomeres. Each cell division results in a progressive shortening of telomeres that, below a certain threshold, promotes genome instability, senescence, and apoptosis. Telomeric erosion, maintenance, and repair take center stage in determining cell fate. Cells of the immune system are under enormous proliferative demand, stressing telomeric intactness. Lymphocytes are capable of upregulating telomerase, an enzyme that can elongate telomeric sequences and, thus, prolong cellular lifespan. Therefore, telomere dynamics are critical in preserving immune function and have become a focus for studies of immunosenescence and autoimmunity. In this review, we describe the role of telomeric nucleoproteins in shaping telomere architecture and in suppressing DNA damage responses. We summarize new insights into the regulation of telomerase activity, hereditary disorders associated with telomere dysfunction, the role of telomere loss in immune aging, and the impact of telomere dysfunction in chronic inflammatory disease.

Innate Immune Responses in the Geriatric Population

“…This study also shows that treatment with statins in patients with high risk on the basis of telomere length results in substantial benefit effect (Brouilette et al, 2007). Oxidative stress is believed to be a major factor of accelerated aging, possible due to an increased pace of telomere shortening resulting from DNA damages observed upon smoking, obesity or cardiovascular diseases (Andrews et al, 2010;Balasubramanyam et al, 2007). The incidence of cancer sharply increases with aging.…”

“…Chronic psychological stress in caregivers of Alzheimer's patients or chronically ill children is associated with telomere loss in peripheral blood lymphocytes, possibly explained by increased cortisol levels. Another study shows reduced telomerase activity related to neuroendocrine and psychosocial data indicative of greater stress (cortisol, epinephrine, norepinephrine) in women but they failed to show an association between telomere shortening and negative mood or education (Andrews et al, 2010;Jiang et al, 2007;Epel et al, 2006). In humans, telomeres shorten by 50-100 base pairs with each cell division.…”

“…Indeed, women present longer telomeres than men. Cortisol inhibits telomerase activity in CD4 and CD8 T cells, suggesting a mechanism by which stress can negatively affect immune response (Andrews et al, 2010;Balasubramanyam et al, 2007). Chronic psychological stress in caregivers of Alzheimer's patients or chronically ill children is associated with telomere loss in peripheral blood lymphocytes, possibly explained by increased cortisol levels.…”

“…Individuals with short telomeres have a 3.18-fold higher mortality rates from heart diseases and 8.54-fold higher mortality rates from infectious diseases compared to those with relatively long telomeres but it is not a significant prognostic factor for survival above 85 years. In addition to telomere shortening with aging, accelerated shortening observed in PBMCs occurs in various human diseases such as myelodysplasic syndrome (Jiang et al, 2007;Andrews et al, 2010;Ohyashiki et al, 1999), atherosclerosis and hypertension (Jiang et al, 2007;Andrews et al, 2010;Benetos et al, 2004), coronary artery disease, human immunodeficiency virus, rheumatoid arthritis (Jiang et al, 2007;Andrews et al, 2010;Steer et al, 2007) systemic lupus erythematosus, cognitive decline,... (Jiang et al, 2007;Andrews et al, 2010). Alzheimer patients present reduced telomere length in PBMCs compared to control.…”

A Nested Case-Controlled Comparison of Telomere Length and Psychological Functioning in Breast Cancer Survivors with and without Insomnia Symptoms

“…The ISI is a seven-item measure of subjective insomnia symptoms in the past 2 weeks and has been validated for use in cancer patients. 7 Considering the association between age, BMI, and TL, 8 each case was matched with a control from the remaining participants who did not report significant insomnia symptoms (ISI score < 7), and were similar in age (within -2 years) and BMI ( -2 units) using the 'psmatching' program through the SPSS R-Plugin. The final sample included 70 women with moderate to severe insomnia symptoms and a matched comparison group of 70 women without insomnia symptoms (n = 140).…”