Kim Jeongjin J, Ahn Alexander, Ying Jeffrey Y, Pollens-Voigt Jesse, Ludlow Andrew T
School of Kinesiology, University of Michigan, Ann Arbor, MI, 48109, USA.
Geroscience. 2024 Sep 2. doi: 10.1007/s11357-024-01319-5.
Telomere shortening occurs with aging in immune cells and may be related to immunosenescence. Exercise can upregulate telomerase activity and attenuate telomere shortening in immune cells, but it is unknown if exercise impacts other immune tissues such as the thymus. This study aimed to examine human telomerase reverse transcriptase (hTERT) alternative splicing (AS) in response to aging and exercise in thymus tissue. Transgenic mice with a human TERT bacterial artificial chromosome integrated into its genome (hTERT-BAC) were utilized in two different exercise models. Mice of different ages were assigned to an exercise cage (running wheel) or not for 3 weeks prior to thymus tissue excision. Middle-aged mice (16 months) were exposed or not to treadmill running (30 min at 60% maximum speed) prior to thymus collection. hTERT transcript variants were measured by RT-PCR. hTERT transcripts decreased with aging (r = - 0.7511, p < 0.0001) and 3 weeks of wheel running did not counteract this reduction. The ratio of exons 7/8 containing hTERT to total hTERT transcripts increased with aging (r = 0.3669, p = 0.0423) but 3 weeks of voluntary wheel running attenuated this aging-driven effect (r = 0.2013, p = 0.4719). Aging increased the expression of senescence marker p16 with no impact of wheel running. Thymus regeneration transcription factor, Foxn1, went down with age with no impact of wheel running exercise. Acute treadmill exercise did not induce any significant changes in thymus hTERT expression or AS variant ratio (p > 0.05). In summary, thymic hTERT expression is reduced with aging. Exercise counteracted a shift in hTERT AS ratio with age. Our data demonstrate that aging impacts telomerase expression and that exercise impacts dysregulated splicing that occurs with aging.
端粒缩短在免疫细胞衰老过程中出现，且可能与免疫衰老相关。运动可上调端粒酶活性并减缓免疫细胞中端粒缩短，但运动是否会影响其他免疫组织（如胸腺）尚不清楚。本研究旨在检测胸腺组织中人类端粒酶逆转录酶（hTERT）可变剪接（AS）对衰老和运动的反应。将整合有人TERT细菌人工染色体的转基因小鼠（hTERT-BAC）用于两种不同的运动模型。在切除胸腺组织前3周，将不同年龄的小鼠分配至运动笼（跑步轮）或不进行运动。中年小鼠（16个月）在采集胸腺前接受或不接受跑步机跑步（以最大速度的60%跑30分钟）。通过RT-PCR检测hTERT转录变体。hTERT转录本随衰老而减少（r = -0.7511，p < 0.0001），3周的跑步轮运动并未抵消这种减少。含hTERT的外显子7/8与总hTERT转录本的比例随衰老而增加（r = 0.3669，p = 0.0423），但3周的自主跑步轮运动减弱了这种衰老驱动的效应（r = 0.2013，p = 0.4719）。衰老增加了衰老标志物p16的表达，跑步轮运动对此无影响。胸腺再生转录因子Foxn1随年龄下降，跑步轮运动对此无影响。急性跑步机运动未引起胸腺hTERT表达或AS变体比例的任何显著变化（p > 0.05）。总之，胸腺hTERT表达随衰老而降低。运动抵消了hTERT AS比例随年龄的变化。我们的数据表明，衰老影响端粒酶表达，运动影响衰老过程中发生的异常剪接。
