Abstract
Background: Telomeres are protective nucleoprotein structures at the end of chromosomes that shorten with age. Telomere length (TL) in peripheral blood mononuclear cells (PBMCs) has been proposed as surrogate marker for TL in the entire organism. Solid evidence that supports this concept is lacking.Methods: Relative TL (RTL) was measured in PBMCS and multiple solid tissues from 24 young (4 months) and 24 aged (14 months) Sprague-Dawley (SD) rats. The mRNA expression of telomerase (TERT) and shelterin proteins TERF-1 and TERF-2 was also measured.Results: Mean RTL in PBMCs and solid tissues of young rats ranged from 0.64 ± 0.26 in large intestine to 1.07 ± 0.22 in skeletal muscle. RTL in PBMCs correlated with that in kidney (r = 0.315, p = 0.008), skeletal muscle (r = 0.276, p = 0.022), liver (r = 0.269, p = 0.033), large intestine (r = −0.463, p = 7.035E-5) and aorta (r = −0.273, p = 0.028). A significant difference of RTL between young and aged animals was only observed in aorta (0.98 ± 0.15 vs. 0.76 ± 0.11, p = 1.987E-6), lung (0.76 ± 0.14 vs. 0.85 ± 0.14, p = 0.024) and visceral fat (0.83 ± 0.14 vs. 0.92 ± 0.15, p = 0.44). The expression of TERT significantly differed between the tested organs with highest levels in liver and kidney. Age-related differences in TERT expression were found in PBMCs, skeletal muscle, and visceral fat. mRNA expression of TERF-1 and TERF-2 was tissue-specific with the highest levels in liver. Age-related differences in TERF-1 and TERF-2 expression were inconsistent.Conclusions: The present study questions the utility of RTL in PBMCs as a biomarker for the individual assessment of aging.
Highlights
Telomeres are protective nucleoprotein structures at the end of chromosomes that shorten with age
Mean Relative TL (RTL) in peripheral blood mononuclear cells (PBMCs) and solid tissues of young rats ranged from 0.64 ± 0.26 in large intestine to 1.07 ± 0.22 in skeletal muscle
Age-related differences in The mRNA expression of telomerase (TERT) expression were found in PBMCs, skeletal muscle, and visceral fat. mRNA expression of TERF-1 and TERF-2 was tissue-specific with the highest levels in liver
Summary
Individuals age at remarkably different rates so that the health status and functional impairment can vary widely at the same chronological age [1]. Telomeres are protective nucleoprotein structures at the ends of eukaryotic chromosomes that are of critical importance for the preservation of our genome [2–4] They are composed by multiple repeats of short noncoding DNA sequences and associated proteins known as shelterins. With the help of shelterins, telomeric DNA folds backward forming a loop structure (t-loop) that allows the single stranded DNA-overhang to invade double-stranded telomeric DNA Together, this prevents DNA repair systems from www.aging-us.com mistaking telomeric ends as DNA strand brakes and from inappropriate attempts to repair them. Results: Mean RTL in PBMCs and solid tissues of young rats ranged from 0.64 ± 0.26 in large intestine to 1.07 ± 0.22 in skeletal muscle. Age-related differences in TERT expression were found in PBMCs, skeletal muscle, and visceral fat. Conclusions: The present study questions the utility of RTL in PBMCs as a biomarker for the individual assessment of aging
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