Biology Department, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia.
Environment and Biomaterial Unit, Health Sciences Research Center, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia.
Int J Mol Sci. 2022 Jan 28;23(3):1499. doi: 10.3390/ijms23031499.
Aging is a complex process indicated by low energy levels, declined physiological activity, stress induced loss of homeostasis leading to the risk of diseases and mortality. Recent developments in medical sciences and an increased availability of nutritional requirements has significantly increased the average human lifespan worldwide. Several environmental and physiological factors contribute to the aging process. However, about 40% human life expectancy is inherited among generations, many lifespan associated genes, genetic mechanisms and pathways have been demonstrated during last decades. In the present review, we have evaluated many human genes and their non-human orthologs established for their role in the regulation of lifespan. The study has included more than fifty genes reported in the literature for their contributions to the longevity of life. Intact genomic DNA is essential for the life activities at the level of cell, tissue, and organ. Nucleic acids are vulnerable to oxidative stress, chemotherapies, and exposure to radiations. Efficient DNA repair mechanisms are essential for the maintenance of genomic integrity, damaged DNA is not replicated and transferred to next generations rather the presence of deleterious DNA initiates signaling cascades leading to the cell cycle arrest or apoptosis. DNA modifications, DNA methylation, histone methylation, histone acetylation and DNA damage can eventually lead towards apoptosis. The importance of calorie restriction therapy in the extension of lifespan has also been discussed. The role of pathways involved in the regulation of lifespan such as DAF-16/FOXO (forkhead box protein O1), TOR and JNK pathways has also been particularized. The study provides an updated account of genetic factors associated with the extended lifespan and their interactive contributory role with cellular pathways.
衰老是一个复杂的过程,表现为能量水平降低、生理活动下降、应激诱导的内稳态丧失,从而增加患病和死亡的风险。医学科学的最新发展和营养需求的增加,显著延长了全球人类的平均寿命。许多环境和生理因素都与衰老过程有关。然而,大约 40%的人类预期寿命是遗传的,在过去几十年中,许多与寿命相关的基因、遗传机制和途径已经得到了证明。在本综述中,我们评估了许多人类基因及其非人类同源基因在调节寿命中的作用。研究包括文献中报道的 50 多个基因,这些基因对延长寿命有贡献。完整的基因组 DNA 是细胞、组织和器官生命活动所必需的。核酸易受氧化应激、化疗和辐射暴露的影响。有效的 DNA 修复机制对于维持基因组完整性至关重要,受损的 DNA不会被复制并传递给下一代,而是有害 DNA 的存在会引发信号级联反应,导致细胞周期停滞或细胞凋亡。DNA 修饰、DNA 甲基化、组蛋白甲基化、组蛋白乙酰化和 DNA 损伤最终可能导致细胞凋亡。限制热量摄入疗法在延长寿命中的作用也得到了讨论。还特别说明了参与寿命调节的途径,如 DAF-16/FOXO(叉头框蛋白 O1)、TOR 和 JNK 途径的作用。该研究提供了与延长寿命相关的遗传因素及其与细胞途径的相互作用的最新概述。