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

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 before (Pre), upon cessation (Post), and during recovery (1, 24, 48, and 72 h; n = 5/time point) from treadmill running (30 min at 60% maximum 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 reverse transcription-polymerase chain reaction methods. SF3B4 and SRSF2 protein expression were measured by Western blotting.

Results: Compared with Pre, FL hTERT increased at Post before decreasing during recovery in the gastrocnemius (48 and 72 h; 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 72 h; 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 in contractile tissues and may maintain telomere length necessary to improve the function and health of the organism.