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175 results on '"Ludlow, Andrew T."'

9. Acute Exercise Regulates hTERT Gene Expression and Alternative Splicing in the hTERT-BAC Transgenic Mouse Model

Author

Slusher, Aaron L., Kim, Jeongjin JJ, Ribick, Mark, and Ludlow, Andrew T.

Subjects
Alternative Splicing, Mice, Physical Conditioning, Animal, Animals, Gene Expression, Humans, Mice, Transgenic, Physical Therapy, Sports Therapy and Rehabilitation, Orthopedics and Sports Medicine, Telomerase, Article
Abstract

INTRODUCTION: Aerobic exercise maintains telomere length through increased human telomerase reverse transcriptase (hTERT) expression and telomerase enzyme activity. The impact of acute exercise on hTERT alternative splicing (AS) is unknown. PURPOSE: This study aimed to examine hTERT AS in response to acute treadmill running. METHODS: A bacterial artificial chromosome mouse model containing the 54 kilobase hTERT gene locus inserted into its genome (hTERT-BAC) was utilized. The gastrocnemius, left ventricle, and brain were excised prior to (Pre), upon cessation (Post), and during recovery (1, 24, 48, and 72H; n = 5/time point) from treadmill running (30 min. at 60% max. speed). Full length (FL) hTERT and the “minus beta” (−β) AS variant (skips exons 7 and 8 and does not code for active telomerase) were measured by gel based and droplet digital RT-PCR methods. SF3B4 and SRSF2 protein expression were measured by western blotting. RESULTS: Compared to Pre, FL hTERT increased at Post before decreasing during recovery in the gastrocnemius (48 and 72H; p ≤ 0.001) and left ventricle (24 h; p = 0.004). The percentage of FL hTERT in the gastrocnemius also increased during recovery (1 and 72H; p ≤ 0.017), whereas a decrease was observed in the left ventricle (1, 24, and 48 h; p ≤ 0.041). hTERT decreased in the brain (48 h), whereas FL hTERT percentage remained unaltered. SF3B4 protein expression decreased throughout recovery in the gastrocnemius and tended to be associated with FL hTERT (r = −0.348, p = 0.075) and −β in opposite directions (r = 0.345, p = 0.067). CONCLUSIONS: Endurance exercise increased hTERT gene expression and altered FL hTERT splicing contractile tissues and may maintain telomere length necessary to improve the function and health of the organism.

Published
2022

48. Telomere length and telomerase activity in T cells are biomarkers of high‐performing centenarians.

Author

Tedone, Enzo, Huang, Ejun, O'Hara, Ryan, Batten, Kimberly, Ludlow, Andrew T., Lai, Tsung‐Po, Arosio, Beatrice, Mari, Daniela, Wright, Woodring E., and Shay, Jerry W.

Subjects
TELOMERES, TELOMERASE, T cells, BIOLOGICAL tags, GENE expression, CENTENARIANS, LONGEVITY
Abstract

It is generally recognized that the function of the immune system declines with increased age and one of the major immune changes is impaired T‐cell responses upon antigen presentation/stimulation. Some "high‐performing" centenarians (100+ years old) are remarkably successful in escaping, or largely postponing, major age‐related diseases. However, the majority of centenarians ("low‐performing") have experienced these pathologies and are forced to reside in long‐term nursing facilities. Previous studies have pooled all centenarians examining heterogeneous populations of resting/unstimulated peripheral blood mononuclear cells (PBMCs). T cells represent around 60% of PBMC and are in a quiescence state when unstimulated. However, upon stimulation, T cells rapidly divide and exhibit dramatic changes in gene expression. We have compared stimulated T‐cell responses and identified a set of transcripts expressed in vitro that are dramatically different in high‐ vs. low‐performing centenarians. We have also identified several other measurements that are different between high‐ and low‐performing centenarians: (a) The amount of proliferation following in vitro stimulation is dramatically greater in high‐performing centenarians compared to 67‐ to 83‐year‐old controls and low‐performing centenarians; (b) telomere length is greater in the high‐performing centenarians; and (c) telomerase activity following stimulation is greater in the high‐performing centenarians. In addition, we have validated a number of genes whose expression is directly related to telomere length and these are potential fundamental biomarkers of aging that may influence the risk and progression of multiple aging conditions. [ABSTRACT FROM AUTHOR]

Published
2019
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