Department of Animal Physiology, Institute of Biology, Pomeranian University in Słupsk, Arciszewski St. 22 B, PL 76-200 Słupsk, Poland.
Biomolecules. 2024 Feb 22;14(3):260. doi: 10.3390/biom14030260.
Anti-ageing biology and medicine programmes are a focus of genetics, molecular biology, immunology, endocrinology, nutrition, and therapy. This paper discusses metabolic therapies aimed at prolonging longevity and/or health. Individual components of these effects are postulated to be related to the energy supply by tricarboxylic acid (TCA) cycle intermediates and free radical production processes. This article presents several theories of ageing and clinical descriptions of the top markers of ageing, which define ageing in different categories; additionally, their interactions with age-related changes and diseases related to α-ketoglutarate (AKG) and succinate SC formation and metabolism in pathological states are explained. This review describes convincingly the differences in the mitochondrial characteristics of energy metabolism in animals, with different levels (high and low) of physiological reactivity of functional systems related to the state of different regulatory systems providing oxygen-dependent processes. Much attention is given to the crucial role of AKG and SC in the energy metabolism in cells related to amino acid synthesis, epigenetic regulation, cell stemness, and differentiation, as well as metabolism associated with the development of pathological conditions and, in particular, cancer cells. Another goal was to address the issue of ageing in terms of individual characteristics related to physiological reactivity. This review also demonstrated the role of the Krebs cycle as a key component of cellular energy and ageing, which is closely associated with the development of various age-related pathologies, such as cancer, type 2 diabetes, and cardiovascular or neurodegenerative diseases where the mTOR pathway plays a key role. This article provides postulates of postischaemic phenomena in an ageing organism and demonstrates the dependence of accelerated ageing and age-related pathology on the levels of AKG and SC in studies on different species (roundworm , , mice, and humans used as models). The findings suggest that this approach may also be useful to show that Krebs cycle metabolites may be involved in age-related abnormalities of the mitochondrial metabolism and may thus induce epigenetic reprogramming that contributes to the senile phenotype and degenerative diseases. The metabolism of these compounds is particularly important when considering ageing mechanisms connected with different levels of initial physiological reactivity and able to initiate individual programmed ageing, depending on the intensity of oxygen consumption, metabolic peculiarities, and behavioural reactions.
抗衰老生物学和医学计划是遗传学、分子生物学、免疫学、内分泌学、营养学和治疗学的重点。本文讨论了旨在延长寿命和/或健康的代谢疗法。这些作用的各个组成部分被假定与三羧酸 (TCA) 循环中间体和自由基产生过程的能量供应有关。本文提出了几种衰老理论和衰老的顶级标志物的临床描述，这些标志物根据不同类别定义衰老；此外，还解释了它们与与α-酮戊二酸 (AKG) 和琥珀酸 SC 形成和代谢相关的年龄相关变化和疾病的相互作用以及病理状态。这篇综述令人信服地描述了不同动物的线粒体能量代谢特征的差异，这些差异与与不同调节系统状态相关的功能系统的生理反应水平（高和低）有关，为依赖氧的过程提供了氧气。非常重视 AKG 和 SC 在与氨基酸合成、表观遗传调控、细胞干性和分化以及与病理条件发展相关的代谢相关的细胞能量代谢中的关键作用，特别是与癌细胞相关的代谢。另一个目标是根据与生理反应相关的个体特征来解决衰老问题。这篇综述还证明了克雷布斯循环作为细胞能量和衰老的关键组成部分的作用，它与各种与年龄相关的病理学的发展密切相关，例如癌症、2 型糖尿病以及心血管或神经退行性疾病，其中 mTOR 途径发挥着关键作用。本文提出了衰老生物体中缺血后现象的假设，并在不同物种（线虫、老鼠和人类作为模型）的研究中证明了 AKG 和 SC 水平对加速衰老和与年龄相关的病理学的依赖性。研究结果表明，这种方法也可能有助于表明克雷布斯循环代谢物可能参与与线粒体代谢相关的与年龄相关的异常，并且因此可能诱导有助于衰老表型和退行性疾病的表观遗传重编程。考虑到与不同初始生理反应水平相关的衰老机制以及能够根据耗氧量、代谢特点和行为反应的强度启动个体编程衰老的能力，这些化合物的代谢尤为重要。
