Vihinen Mauno
Department of Experimental Medical Science, Lund University, BMC B13, Lund, SE-221 84, Sweden.
F1000Res. 2022 Apr 13;11:419. doi: 10.12688/f1000research.110944.2. eCollection 2022.
A substantial portion of molecules in an organism are involved in regulation of a wide spectrum of biological processes. Several models have been presented for various forms of biological regulation, including gene expression regulation and physiological regulation; however, a generic model is missing. Recently a new unifying theory in biology, poikilosis, was presented. Poikilosis indicates that all systems display intrinsic heterogeneity. The concept of poikilosis allowed development of a model for biological regulation applicable to all types of regulated systems. The perturbation-lagom-TATAR countermeasures-regulator (PLTR) model combines the effects of perturbation and lagom (allowed and sufficient extent of heterogeneity) in a system with tolerance, avoidance, repair, attenuation and resistance (TARAR) countermeasures, and possible regulators. There are three modes of regulation, two of which are lagom-related. In the first scenario, lagom is maintained, both intrinsic (passive) and active TARAR countermeasures can be involved. In the second mode, there is a shift from one lagom to another. In the third mode, reguland regulation, the regulated entity is the target of a regulatory shift, which is often irreversible or requires action of another regulator to return to original state. After the shift, the system enters to lagom maintenance mode, but at new lagom extent. The model is described and elaborated with examples and applications, including medicine and systems biology. Consequences of non-lagom extent of heterogeneity are introduced, along with a novel idea for therapy by reconstituting biological processes to lagom extent, even when the primary effect cannot be treated.
生物体中的很大一部分分子参与了广泛生物过程的调节。针对各种形式的生物调节，包括基因表达调节和生理调节，已经提出了几种模型；然而，尚缺乏一个通用模型。最近，生物学领域提出了一种新的统一理论——“异质性理论”。异质性理论表明，所有系统都表现出内在的异质性。异质性理论的概念使得能够开发出一种适用于所有类型调节系统的生物调节模型。扰动-适度-应对措施-调节器（PLTR）模型将系统中扰动和适度（允许且充分的异质性程度）的影响与耐受、回避、修复、衰减和抵抗（TARAR）应对措施以及可能的调节器结合起来。存在三种调节模式，其中两种与适度相关。在第一种情况下，适度得以维持，可能涉及内在（被动）和主动的TARAR应对措施。在第二种模式中，从一种适度状态转变为另一种适度状态。在第三种模式，即被调节物调节中，被调节实体是调节转变的目标，这种转变通常是不可逆的，或者需要另一个调节器的作用才能恢复到原始状态。转变之后，系统进入适度维持模式，但处于新的适度程度。该模型通过实例和应用进行了描述和阐述，包括医学和系统生物学。文中介绍了异质性程度不符合适度的后果，以及一种新的治疗思路，即即使主要效应无法治疗，也可通过将生物过程重建到适度程度来进行治疗。
