Telomere length in leucocytes and solid tissues of young and aged rats

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.

Molecular and Structural Alterations of Skeletal Muscle Tissue Nuclei during Aging

“…Similarly, the detection of telomere restriction fragments by hybridization to a 32 P-TTAGGG probe did not reveal any alteration in the mean telomere lengths of masseter and biceps muscles of elderly humans in comparison to young counterparts [150]. Moreover, no age-related difference in the mRNA expression of both TRF1 (terminal restriction fragment 1) and TRF2 was highlighted in rat muscles [151]; However, the mRNA expression of telomerase, an enzyme that elongates telomeres, was slightly higher in the same aged muscle [151].…”

“…This finding is consistent with the fact that skeletal muscle fibers ha very long lifespan and contain post-mitotic myonuclei that have undergone a few m divisions before differentiation, thus keeping the telomere length relatively constant unchanged. Similarly, the detection of telomere restriction fragments by hybridizatio a 32 P-TTAGGG probe did not reveal any alteration in the mean telomere lengths of seter and biceps muscles of elderly humans in comparison to young counterparts [ Moreover, no age-related difference in the mRNA expression of both TRF1 (termina striction fragment 1) and TRF2 was highlighted in rat muscles [151]; However, the mR expression of telomerase, an enzyme that elongates telomeres, was slightly higher in same aged muscle [151].…”

Telomere length is not a useful tool for chronological age estimation in animals

“…Although TL may vary considerably in different tissues, TLs and shortening rates are often modestly correlated across tissues, [38,103,104] but there are exceptions to the use of, for example, blood TL as a proxy for other tissues. [105] A range of methods to quantify TL have been developed, which produce different types of information on the average, distribution, chromosome-specific, absolute or relative, interstitial or functional TLs (reviewed in [106,107] ). The telomere restriction fragment (TRF) assay allows estimating the mean and distribution of absolute TLs across all chromosomes, which may reveal TL dynamics beyond the mean TL.…”

A Unified Model of Age-Related Cardiovascular Disease

“…Contributing to the confusion, many studies analyze aging in cells that are not responsible for the disease [ 138 , 139 ]. Because of sample collection simplicity, circulating leukocytes rather than vascular endothelial cells are commonly analyzed for telomere attrition [ 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 ].…”