What Is the Theoretical Upper Age Limit of Humans? Blood Cell Counts and Footsteps May Offer a Clue

人类理论上的年龄上限是多少?血细胞计数和脚步声可能提供线索

最终有些事情会害死你——可能是癌症、糖尿病或雷击。但是,如果在一个完美的世界中,您能够避免所有这些灾难,摆脱那些损害您健康的日常压力,并真正死于“老年”,该怎么办?

之前有大量研究调查过这个问题,目前我们对衰老与生理变量变化之间复杂关系的理解大部分来自大型横断面研究,并导致所谓的“生物钟”的准确性不断提高“ 将人类长寿因素建立在血液标记物、DNA 和运动活动模式的基础上。

当然,衰老的许多特征——干细胞耗竭、细胞间通讯改变、表观遗传改变和基因组不稳定——都可以通过药物来解决。但如果你真的想活得更长,需要的不仅仅是药物和疗法,因为还必须解决这些衰老特征的恢复率。

2021 年 5 月,新加坡生物技术公司 Gero 的一个研究团队与纽约布法罗的罗斯威尔公园综合癌症中心合作,提出了一项关于衰老与丧失从日常压力中恢复的能力之间关系的研究结果。

研究结果包括对如果一切顺利的话人类可以活多久的估计,它们可能会让你感到惊讶。

 

你能活多久?这个答案取决于“韧性”


在这项发表在《自然通讯》杂志上的研究中,Gero研究员 Timothy Pyrkov 及其同事研究了来自美国的大量人群的“衰老速度”。 、英国和俄罗斯。他们通过评估血细胞计数的变化和每日行走的步数来评估稳定健康状况的偏差,然后按年龄组进行分析。

 

Toxic stres, hormetic stress and the rate of aging

 


对于血细胞和步数,研究人员发现模式是相同的:随着年龄的增长,与疾病无关的一个因素会导致身体在中断后将血细胞或步态恢复到稳定水平的能力出现可预测的下降。 。皮尔科夫和他的同事随后绘制了这种逐渐下降的图表,直至恢复力完全消失,并将其视为死亡的年龄。

结果?

“这一趋势的推断表明,动态有机体状态指标 (DOSI) 恢复时间和方差将在 120-150 的临界点同时发散相当于完全丧失弹性的年龄,”作者写道,并补充说,这一观察结果通过对可穿戴设备收集的日内体力活动水平波动的相关特性进行的独立分析得到了证实。

值得注意的是,研究人员的相关性是这一发现的关键。血细胞计数和血压等测量值都有已知的健康范围,而步数对于每个人来说都是独一无二的。事实上,随着时间的推移,步数和血细胞计数显示出同样的下降,这使得它们成为真正的衰老速度工具。

 

 

失去弹性对最长寿命意味着什么

 

社会因素也支持了该研究的结果。 40 岁的人的恢复时间约为 2 周,但 80 岁的人则需要 6 周。预测的复原力损失,即使是那些最健康的人,也可以解释为什么这个最长寿命最终不会增加,尽管平均寿命正在稳步增加(或者至少在大规模死亡人数出现之前)。 2019冠状病毒病)。

这也意味着,任何不影响复原力下降的干预措施也不会有效延长最大寿命——相反,我们只会看到人类寿命的逐步增加。

 

一份详细介绍这项研究的新闻稿指出:“因此,如果不阻止衰老过程,即弹性丧失的根本原因,就不可能通过预防或治疗疾病来大幅延长寿命。我们预计没有任何自然法则禁止这种干预。因此,这项研究中提出的衰老模型可以指导开发对健康寿命具有最大影响的延长寿命疗法。”

 

对衰老的新认识


该研究的作者展示了他们对人类如何衰老的解释的示意图,年龄与动态有机体状态指标相对应,就像一条在再生和受伤或疾病之间碰撞的流动线,随着人类失去恢复能力,两者之间的偏差越来越大来自震惊和压力。

 

SCHEMATIC ILLUSTRATION OF LOSS OF RESILIENCE ALONG AGING TRAJECTORIES


他们在研究中写道:“远离临界点(在年轻时),有机体状态扰动可以被​​认为仅限于势能盆地中可能的稳定平衡状态附近。” “最初,动态稳定性是由足够高的势能屏障提供的,该势垒将该稳定盆地与生理参数空间中不可避免地存在的动态不稳定区域分开。健康跨度状态经历与亚稳态平衡状态的随机偏差,该状态逐渐被取代在衰老过程中,即使对于成功衰老的个体来说也是如此”。

他们解释说,在压力存在的情况下,弹性的丧失会导致身体健康状态的不稳定。当保护屏障被跨越时,稳定性就会丧失,“并且生理参数的偏差会超出控制,导致多种发病,并最终导致死亡。因此,健康期限的结束可以被视为成核过渡的一种形式,相应的在我们的例子中,慢性疾病状态在亚稳态阶段(健康有机体)的自发形成”。

那么作者提出可以采取什么措施来延长寿命?他们指出了针对与虚弱相关的表型(例如炎症)的疗法。对于那些身体虚弱的人来说,这种干预措施将产生持久的影响并减少虚弱程度,从而延长健康寿命之外的寿命。

 

参考:

 

1. Levine, M. E. 衰老率建模:估计的生物年龄能否比实足年龄更准确地预测死亡率? J.杰龙托尔。生物。科学。医学。科学。 68, 667–674 (2013)。

2. Aleksandr, Z. 等人。鉴定与人类健康寿命相关的 12 个基因位点。交流。生物。 2, 1–11 (2019)。

3. Mitnitski, A. & Rockwood, K. 衰老速度:赤字积累速度在成人寿命期间不会改变。生物老年学 17, 199–204 (2016)。

4. 萨德洛,C.等人。英国生物银行:一种开放获取资源,用于确定中老年各种复杂疾病的原因。公共科学图书馆医学。 12、e1001779 (2015)。

5. Horvath, S. 人体组织和细胞类型的 DNA 甲基化年龄。基因组生物学。 14,R115(2013)。

6. Gijzel, S. M. W. 等人。临床护理的弹性:掌握老年人的康复潜力。 J. Am.老年病。苏克。 67, 2650–2657 (2019)。

7. Lippi, G., Salvagno, G. L. & Guidi, G. C. 红细胞分布宽度与衰老和性别显着相关。临床。化学。劳动。医学。 (章法委)52,e197-e199(2014 年)。

8. Levine, M. E. 等人。寿命和健康寿命衰老的表观遗传生物标志物。老龄化(纽约州奥尔巴尼)10, 573 (2018)。

9. Avchaciov, K. 等人。通过深度学习小鼠大型表型数据集中的衰老轨迹,识别基于血液测试的衰老生物标志物。 BioRxiv 预印本 https://doi.org/10.1101/2020.01.23.917286 (2020)。

10. Pyrkov, T.V. 和 Fedichev, P.O.生物年龄是衰老、压力和虚弱的普遍标志。人类衰老的生物标志物,23-36(Springer,2019)。

11.贝尔斯基,D.W.等人。年轻人生物衰老的量化。过程。国家科学院。科学。 112,E4104–E4110(2015)。

12. Sara, A。通过深度纵向分析揭示的个人衰老标记和年龄型。纳特。医学。 26, 83–90 (2020)。

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