Steiner Ulrich Karl
Evolutionary Demography Group, Institute of Biology, Freie Universität Berlin, Berlin, Germany.
Front Cell Dev Biol. 2021 Jun 18;9:668915. doi: 10.3389/fcell.2021.668915. eCollection 2021.
Bacteria have been thought to flee senescence by dividing into two identical daughter cells, but this notion of immortality has changed over the last two decades. Asymmetry between the resulting daughter cells after binary fission is revealed in physiological function, cell growth, and survival probabilities and is expected from theoretical understanding. Since the discovery of senescence in morphologically identical but physiologically asymmetric dividing bacteria, the mechanisms of bacteria aging have been explored across levels of biological organization. Quantitative investigations are heavily biased toward and on the role of inclusion bodies-clusters of misfolded proteins. Despite intensive efforts to date, it is not evident if and how inclusion bodies, a phenotype linked to the loss of proteostasis and one of the consequences of a chain of reactions triggered by reactive oxygen species, contribute to senescence in bacteria. Recent findings in bacteria question that inclusion bodies are only deleterious, illustrated by fitness advantages of cells holding inclusion bodies under varying environmental conditions. The contributions of other hallmarks of aging, identified for metazoans, remain elusive. For instance, genomic instability appears to be age independent, epigenetic alterations might be little age specific, and other hallmarks do not play a major role in bacteria systems. What is surprising is that, on the one hand, classical senescence patterns, such as an early exponential increase in mortality followed by late age mortality plateaus, are found, but, on the other hand, identifying mechanisms that link to these patterns is challenging. Senescence patterns are sensitive to environmental conditions and to genetic background, even within species, which suggests diverse evolutionary selective forces on senescence that go beyond generalized expectations of classical evolutionary theories of aging. Given the molecular tool kits available in bacteria, the high control of experimental conditions, the high-throughput data collection using microfluidic systems, and the ease of life cell imaging of fluorescently marked transcription, translation, and proteomic dynamics, in combination with the simple demographics of growth, division, and mortality of bacteria, make the challenges surprising. The diversity of mechanisms and patterns revealed and their environmental dependencies not only present challenges but also open exciting opportunities for the discovery and deeper understanding of aging and its mechanisms, maybe beyond bacteria and aging.
人们一直认为细菌通过分裂成两个完全相同的子细胞来逃避衰老，但在过去二十年里，这种长生不老的观念已经发生了变化。二分裂后产生的子细胞在生理功能、细胞生长和存活概率上表现出不对称性，从理论理解上看这是可以预期的。自从在形态相同但生理上不对称分裂的细菌中发现衰老现象以来，人们已经从生物组织的各个层面探索了细菌衰老的机制。定量研究严重偏向并集中于包涵体（错误折叠蛋白质的聚集体）的作用。尽管迄今为止人们付出了巨大努力，但尚不清楚与蛋白质稳态丧失相关的表型、由活性氧引发的一系列反应的后果之一——包涵体是否以及如何导致细菌衰老。细菌领域的最新发现对包涵体仅仅有害这一观点提出了质疑，例如在不同环境条件下，含有包涵体的细胞具有适应性优势就说明了这一点。对于后生动物确定的其他衰老标志的作用仍不明确。例如，基因组不稳定性似乎与年龄无关，表观遗传改变可能几乎没有年龄特异性，其他标志在细菌系统中也不发挥主要作用。令人惊讶的是，一方面发现了经典的衰老模式，如死亡率早期呈指数级上升，随后在晚年趋于平稳，但另一方面，确定与这些模式相关的机制具有挑战性。衰老模式对环境条件和遗传背景敏感，即使在同一物种内也是如此，这表明衰老受到多种进化选择力量的影响，超出了经典衰老进化理论的一般预期。鉴于细菌可用的分子工具包、对实验条件的高度控制、使用微流控系统进行的高通量数据收集以及对荧光标记的转录、翻译和蛋白质组动力学进行活细胞成像的便利性，再加上细菌生长、分裂和死亡的简单统计学特征，这些挑战令人惊讶。所揭示的机制和模式的多样性及其对环境的依赖性不仅带来了挑战，也为发现和更深入理解衰老及其机制提供了令人兴奋的机会，也许这一发现范围会超越细菌和衰老领域。
