甲基化时钟用于评估抗衰老干预措施。

IF 3.9 3区 医学 Q2 CELL BIOLOGY
Aging-Us Pub Date : 2025-05-05 DOI:10.18632/aging.206245
Josh Mitteldorf
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引用次数: 0

摘要

甲基化时钟已经进入衰老研究领域,作为一种测试抗衰老干预措施的方法,而不必等待死亡率统计数据。但甲基化是表观遗传控制的主要手段,并且可能是在强选择下进化的。因此,如果甲基化模式在晚年持续变化,这一定意味着两种情况之一。要么(1)身体进化为自我毁灭(通过炎症、自身免疫等),而观察到的甲基化变化是达到这一目的的手段;或者(2)身体检测到累积的损伤,并在一场拯救自己的运动中加速修复机制。我在这里的论点是,1型和2型变化都在发生,但只有1型变化对构建甲基化时钟以评估抗衰老干预措施有用。这是因为一种将1型糖尿病的变化推迟到更早年龄状态的疗法已经阻止了身体自我毁灭;但一种阻碍2型糖尿病变化的疗法已经阻止了身体自我修复。因此,表观遗传时钟开发人员面临的一个主要挑战是区分2型和1型。1型表观遗传变化的存在与传统的达尔文思想相冲突,这促使一些研究人员探索1型变化可能是随机表观遗传漂变的一种形式的可能性。我在此认为,看起来像是定向表观遗传变化的东西实际上是定向表观遗传变化。在最近五篇关于“随机甲基化时钟”的文章中,只有一篇(来自康博伊实验室)是基于真正的随机变化。使用Conboy方法和甲基化数据库,我构建了一个真正的甲基化漂移的测量,并表明它与年龄的相关性太低而无用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Methylation clocks for evaluation of anti-aging interventions.

Methylation clocks have found their way into the community of aging research as a way to test anti-aging interventions without having to wait for mortality statistics. But methylation is a primary means of epigenetic control, and presumably has evolved under strong selection. Hence, if methylation patterns change consistently at late ages it must mean one of two things. Either (1) the body is evolved to destroy itself (with inflammation, autoimmunity, etc.), and the observed methylation changes are a means to this end; or (2) the body detects accumulated damage, and is ramping up repair mechanisms in a campaign to rescue itself. My thesis herein is that both Type 1 and Type 2 changes are occurring, but that only Type 1 changes are useful in constructing methylation clocks to evaluate anti-aging interventions. This is because a therapy that sets back Type 1 changes to an earlier age state has stopped the body from destroying itself; but a therapy that sets back Type 2 changes has stopped the body from repairing itself. Thus, a major challenge before the community of epigenetic clock developers is to distinguish Type 2 from Type 1. The existence of Type 1 epigenetic changes is in conflict with conventional Darwinian thinking, and this has prompted some researchers to explore the possibility that Type 1 changes might be a form of stochastic epigenetic drift. I argue herein that what seems like directed epigenetic change really is directed epigenetic change. Of five recent articles on "stochastic methylation clocks," only one (from the Conboy lab) is based on truly stochastic changes. Using the Conboy methodology and a methylation database, I construct a measure of true methylation drift, and show that its correlation with age is too low to be useful.

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来源期刊
Aging-Us
Aging-Us CELL BIOLOGY-
CiteScore
10.00
自引率
0.00%
发文量
595
审稿时长
6-12 weeks
期刊介绍: Information not localized
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