Short Telomeres in Patients with Vascular Dementia: An Indicator of Low Antioxidative Capacity and a Possible Risk Factor?

Abstract

SUMMARY:Progressive cerebrovascular atherosclerosis and consecutive stroke are among the most common causes of dementia. However, specific risk factors for vascular dementia are still not known. Human telomeres shorten with each cell division in vitro and with donor age in vivo. In human fibroblasts in vitro, the telomere shortening rate decreased with increasing antioxidative capacity. There was a good intra-individual correlation between the age-corrected telomere lengths in fibroblasts and peripheral blood mononuclear cells. In 186 individuals including 149 geriatric patients (age range, 55-98 yr), leukocyte telomeres in patients with probable or possible vascular dementia were significantly shorter than in three age-matched control groups, namely in cognitively competent patients suffering from cerebrovascular or cardiovascular disease alone, in patients with probable Alzheimer's dementia, and in apparently healthy control subjects. No correlation was found to polymorphisms in the apolipoprotein E and glutathione-S-transferase genes. Telomere length may be an independent predictor for the risk of vascular dementia. (Lab Invest 2000, 80:1739 -1747.P rogressive cerebrovascular atherosclerosis and consecutively stroke are the second most common causes of dementia in Europe and the United States, and the most common causes in Asia and in many developing countries (Konno et al, 1997). The search for prognostic factors for late-onset dementia, and especially those with a vascular component, is a high research priority because (a) dementia is a major burden to any "greying" society, (b) stroke and vascular risk factors are not only causal for vascular dementia (VaD) but also contribute to the pathogenesis of significant fractions of both Alzheimer's dementia (AD) and dementia with Lewy bodies cases, (c) dementia associated with stroke and vascular risk might be treatable or even preventable if patients at high risk could be identified early enough, (d) apart from age, there are no well-documented risk factors specifically for vascular dementia (Gorelick, 1997), and (e) the penetrance of identified or suspected genetic risk factors for late-onset dementia varies widely, limiting their use as prognostic factors.Telomeres in somatic human cells shorten with each cell division in vitro, and telomere length in peripheral blood mononuclear cells (PBMC) (Frenck et al, 1998;Rufer et al, 1999) or endothelial cells (Chang and Harley, 1995) decreases with age. In immortal cells, including the vast majority of tumors, telomere shortening is counteracted by the activation of telomerase or, in few cases, of an alternative mechanism (Prescott and Blackburn, 1999). Ectopic expression of telomerase is sufficient to immortalize at least some human cells (Bodnar et al, 1998). Together, this data suggests a key role for telomeres as a biological clock, counting the successive rounds of replication and eventually triggering senescence in human cells. Maintenance of telomeres has been causally implicated in both hyperproliferative and h...

Offspring's Leukocyte Telomere Length, Paternal Age, and Telomere Elongation in Sperm

“…Environmental factors, including smoking [3,10], obesity [9][10][11], psychological stress [12] and low socio-economic status (SES) [13] are ostensibly associated with shortened LTL, underscoring the roles of not only genetic factors but also the environment in fashioning leukocyte telomere dynamics (length and attrition rate). Shortened LTL is also observed in individuals with aging-related diseases, including hypertension [1,7], insulin resistance [11,14,15], atherosclerosis [16,17], myocardial infarction [16,18,19], stroke [9] and dementia [20,21]. Further, aging itself may modify the relationship between LTL and some of these variables [reviewed 22].…”

Oxidative stress causes telomere damage in Fanconi anaemia cells – a possible predisposition for malignant transformation

“…This shortening was more pronounced in cells of patients with ataxia-telangiectasia (Tchirkov & Lansdorp, 2003). The accelerated telomere shortening described in several clinical conditions, such as various vascular diseases (Von Zglinicki et al, 2000b;Brummendorf et al, 2001 andSamani et al, 2001) and chronic stress conditions (Epel et al, 2004(Epel et al, , 2006, was attributed mainly to oxidative stress.…”

Aging of perennial cells and organ parts according to the programmed aging paradigm

“…In fact, telomeres have been shown to be significantly shorter in patients with probable AD than in apparently healthy control subjects (von Zglinicki et al 2000). Moreover, there is an association between AD and cardiovascular risk factors (Vogel et al 2006;Rosendorff et al 2007).…”