生物体生命和衰老的起点。
The Ground Zero of Organismal Life and Aging.
机构信息
Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
出版信息
Trends Mol Med. 2021 Jan;27(1):11-19. doi: 10.1016/j.molmed.2020.08.012. Epub 2020 Sep 23.
Abstract
Cells may naturally proceed or be forced to transition to a state with a radically lower biological age, that is, be rejuvenated. Examples are the conversion of somatic cells to induced pluripotent stem cells and rejuvenation of the germline with each generation. We posit that these processes converge to the same 'ground zero', the mid-embryonic state characterized by the lowest biological age where both organismal life and aging begin. It may also be related to the phylotypic state. The ground zero model clarifies the relationship between aging, development, rejuvenation, and de-differentiation, which are distinct throughout life. By extending the rejuvenation phase during early embryogenesis and editing the genome, it may be possible to achieve the biological age at the ground zero lower than that achieved naturally.
摘要
细胞可能会自然地或被迫转变为生物学年龄显著降低的状态，也就是被“返老还童”。体细胞被诱导转化为多能干细胞和生殖系每一代的更新就是这样的例子。我们假设这些过程都汇聚到同一个“基准点”，即具有最低生物学年龄的中胚胎状态，在这个状态中，生物体的生命和衰老同时开始。它也可能与表型状态有关。基准点模型阐明了衰老、发育、返老还童和去分化之间的关系，这些在整个生命过程中都是不同的。通过在早期胚胎发生过程中延长返老还童阶段并编辑基因组，有可能使生物学年龄达到比自然状态更低的基准点。
相似文献
1
The Ground Zero of Organismal Life and Aging.生物体生命和衰老的起点。
Trends Mol Med. 2021 Jan;27(1):11-19. doi: 10.1016/j.molmed.2020.08.012. Epub 2020 Sep 23.
2
Epigenetic clocks reveal a rejuvenation event during embryogenesis followed by aging.表观遗传时钟揭示了胚胎发生过程中的一次年轻化事件，随后是衰老。
Sci Adv. 2021 Jun 25;7(26). doi: 10.1126/sciadv.abg6082. Print 2021 Jun.
3
Reversibility of irreversible aging.逆转不可逆转的衰老。
Ageing Res Rev. 2019 Jan;49:104-114. doi: 10.1016/j.arr.2018.11.008. Epub 2018 Dec 1.
4
The beginning of becoming a human.人类的起源。
Aging (Albany NY). 2024 May 6;16(9):8378-8395. doi: 10.18632/aging.205824.
5
Combining rejuvenation interventions in rodents: a milestone in biomedical gerontology whose time has come.将衰老干预措施相结合：生物医学老年学的一个里程碑，现在是时候了。
Expert Opin Ther Targets. 2024 Jun;28(6):501-511. doi: 10.1080/14728222.2024.2330425. Epub 2024 Mar 18.
6
Age reprogramming and epigenetic rejuvenation.年龄重编程和表观遗传复壮。
Epigenetics Chromatin. 2018 Dec 20;11(1):73. doi: 10.1186/s13072-018-0244-7.
7
How can aging be reversed? Exploring rejuvenation from a damage-based perspective.衰老如何逆转？从基于损伤的角度探索年轻化。
Adv Genet (Hoboken). 2020 Aug 10;1(1):e10025. doi: 10.1002/ggn2.10025. eCollection 2020 Dec.
8
Intersection clock reveals a rejuvenation event during human embryogenesis.交集时钟揭示了人类胚胎发生过程中的一个年轻化事件。
Aging Cell. 2023 Oct;22(10):e13922. doi: 10.1111/acel.13922. Epub 2023 Oct 2.
9
Rejuvenation in distinct cell populations - What does it mean?不同细胞群体的年轻化——这意味着什么？
Exp Gerontol. 2009 Oct;44(10):634-8. doi: 10.1016/j.exger.2009.07.006. Epub 2009 Jul 26.
10
Rejuvenation of Cardiac Tissue Developed from Reprogrammed Aged Somatic Cells.重编程衰老体细胞所发育的心脏组织的年轻化
Rejuvenation Res. 2017 Oct;20(5):389-400. doi: 10.1089/rej.2017.1930. Epub 2017 Jun 20.
引用本文的文献
1
A Biophysics of Epigenetic Rejuvenation.表观遗传年轻化的生物物理学
Cells. 2025 Aug 13;14(16):1249. doi: 10.3390/cells14161249.
2
Aging and immunity: the age-old tango.衰老与免疫：古老的探戈舞。
Genes Dev. 2025 Aug 1;39(15-16):948-974. doi: 10.1101/gad.352644.125.
3
DNA methylation-based age prediction and sex-specific epigenetic aging in a lizard with female-biased longevity.基于DNA甲基化的年龄预测及具有雌性偏长寿特征蜥蜴的性别特异性表观遗传衰老
Sci Adv. 2025 Jan 31;11(5):eadq3589. doi: 10.1126/sciadv.adq3589.
4
Epigenetic rejuvenation: a journey backwards towards an epigenomic ground state.表观遗传重焕活力：迈向表观基因组基态的逆向旅程。
Epigenomics. 2025 Jan;17(1):1-3. doi: 10.1080/17501911.2024.2432851. Epub 2024 Nov 25.
5
Profiling the transcriptomic age of single-cells in humans.人类单细胞转录组时代的剖析。
Commun Biol. 2024 Oct 26;7(1):1397. doi: 10.1038/s42003-024-07094-5.
6
Epistemic uncertainty challenges aging clock reliability in predicting rejuvenation effects.认知不确定性挑战了衰老时钟预测年轻化效果的可靠性。
Aging Cell. 2024 Nov;23(11):e14283. doi: 10.1111/acel.14283. Epub 2024 Jul 28.
7
Aging clocks based on accumulating stochastic variation.基于累积随机变化的衰老时钟。
Nat Aging. 2024 Jun;4(6):871-885. doi: 10.1038/s43587-024-00619-x. Epub 2024 May 9.
8
The beginning of becoming a human.人类的起源。
Aging (Albany NY). 2024 May 6;16(9):8378-8395. doi: 10.18632/aging.205824.
9
Early origins of health and disease risk: The case for investigating adverse exposures and biological aging in utero, across childhood, and into adolescence.健康与疾病风险的早期起源：关于研究子宫内、儿童期及青春期不良暴露与生物衰老的案例
Child Dev Perspect. 2023 Dec;17(3-4):149-156. doi: 10.1111/cdep.12488. Epub 2023 Oct 16.
10
Multi-omics characterization of partial chemical reprogramming reveals evidence of cell rejuvenation.多组学特征分析部分化学重编程揭示细胞年轻化的证据。
Elife. 2024 Mar 22;12:RP90579. doi: 10.7554/eLife.90579.
本文引用的文献
1
How can aging be reversed? Exploring rejuvenation from a damage-based perspective.衰老如何逆转？从基于损伤的角度探索年轻化。
Adv Genet (Hoboken). 2020 Aug 10;1(1):e10025. doi: 10.1002/ggn2.10025. eCollection 2020 Dec.
2
Germline burden of rare damaging variants negatively affects human healthspan and lifespan.种系负担的罕见有害变异会对人类的健康寿命和寿命产生负面影响。
Elife. 2020 Apr 7;9:e53449. doi: 10.7554/eLife.53449.
3
Patterns of Aging Biomarkers, Mortality, and Damaging Mutations Illuminate the Beginning of Aging and Causes of Early-Life Mortality.衰老生物标志物、死亡率和有害突变模式阐明了衰老的开始和早逝的原因。
Cell Rep. 2019 Dec 24;29(13):4276-4284.e3. doi: 10.1016/j.celrep.2019.11.091.
4
Mice with hyper-long telomeres show less metabolic aging and longer lifespans.端粒超长的小鼠表现出较低的代谢衰老和更长的寿命。
Nat Commun. 2019 Oct 17;10(1):4723. doi: 10.1038/s41467-019-12664-x.
5
Toward a unified theory of aging and regeneration.走向衰老与再生的统一理论。
Regen Med. 2019 Sep;14(9):867-886. doi: 10.2217/rme-2019-0062. Epub 2019 Aug 28.
6
Emergence of structure in mouse embryos: Structural Entropy morphometry applied to digital models of embryonic anatomy.鼠胚胎结构的形成：结构熵形态计量学在胚胎解剖数字模型中的应用。
J Anat. 2019 Oct;235(4):706-715. doi: 10.1111/joa.13031. Epub 2019 Jul 5.
7
Adopt a moratorium on heritable genome editing.暂停可遗传的基因组编辑。
Nature. 2019 Mar;567(7747):165-168. doi: 10.1038/d41586-019-00726-5.
8
Synchrony and asynchrony between an epigenetic clock and developmental timing.表观遗传时钟与发育时间的同步和不同步。
Sci Rep. 2019 Mar 6;9(1):3770. doi: 10.1038/s41598-019-39919-3.
9
Ribosomal DNA harbors an evolutionarily conserved clock of biological aging.核糖体 DNA 携带着进化上保守的生物衰老时钟。
Genome Res. 2019 Mar;29(3):325-333. doi: 10.1101/gr.241745.118. Epub 2019 Feb 14.
10
Optimal-Transport Analysis of Single-Cell Gene Expression Identifies Developmental Trajectories in Reprogramming.最优传输分析单细胞基因表达鉴定重编程中的发育轨迹。
Cell. 2019 Feb 7;176(4):928-943.e22. doi: 10.1016/j.cell.2019.01.006. Epub 2019 Jan 31.
Zotero 插件