禁食诱导的长寿效应的遗传调节
Alison Luciano1, Laura Robinson1, William H Schott1
1The Jackson Laboratory, Bar Harbor, ME, USA.
bioRxiv : the preprint server for biology
|September 15, 2025
概括
间歇性禁食 (IF) 反应因小鼠的性别和遗传背景而有显著差异. 了解这些遗传因素对于安全地将IF的好处转化为人类健康和寿命至关重要.
科学领域:
- 生物老龄化 生物老龄化
- 遗传学 是一个遗传学.
- 营养科学 营养科学
背景情况:
- 像卡路里限制和间歇性禁食 (IF) 这样的饮食干预措施对代谢健康和寿命延长有希望.
- 个人对IF的反应变异性会影响其在人类中的安全性和有效性,但仍然不太了解.
- 协作交叉 (CC) 鼠标模型提供了一个多样化的遗传平台来研究干预反应异质性.
研究的目的:
- 研究遗传背景和性别对间歇性禁食 (IF) 的生理和寿命反应的影响.
- 为了确定IF响应是否是基因决定的,使用多样化的小鼠模型.
- 为了比较杂交的CC小鼠和杂交的多样性杂交 (DO) 小鼠之间的发现.
主要方法:
- 在10种内生菌株 (n=800) 的协作交叉 (CC) 小鼠中实施了每周两天间歇性禁食 (IF) 方案.
- 进行了纵向表型鉴定,以评估数百种特征,包括寿命.
- 将结果与使用多样性异种 (DO) 老鼠的并行研究进行比较.
主要成果:
- 性别和遗传背景显著影响了对IF的生理反应,包括新陈代谢,血液学和免疫学参数.
- 发现IF对寿命的影响是性别特异的,并且在不同的遗传背景下有所不同.
- 确定了健康和寿命的关键预测因素,在内生和外生小鼠模型之间存在显著差异.
结论:
- 间歇性禁食反应是基因决定的,正如在临床前模型中证明的那样,具有类似人类的生理特征.
- 遗传因素在决定个人对IF等饮食干预措施的反应方面发挥着关键作用.
- 这些发现为个人转化IF对人类健康和寿命的好处提供了必要的见解.
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