Feltes Bruno César
Institute of Biosciences, Department of Biophysics, Universidade Federal Do Rio Grande Do Sul - UFRGS, Avenida Bento Gonçalves 9500 - Prédio 43422, Sala 218, Porto Alegre, Rio Grande Do Sul, 91509-900, Brazil.
Biogerontology. 2025 May 5;26(3):105. doi: 10.1007/s10522-025-10243-w.
The neuronal tissue is notable for its unique regulation of the immune system, response to DNA damage, endurance against reactive oxygen and nitrogen species, and control of inflammatory pathways. Here, I discuss some uniqueness of the brain's aging process in light of the free radical theory of aging, DNA-damage accumulation, inflammaging, and aging as a consequence of a programmed developmental process. Key points include (i) the resilience of the neuronal tissue to oxidative stress; (ii) the neuron's efficiency in repairing learning-induced DNA damage, even with fewer repair pathways than other cell types; (iii) TLR9 and NFκB at the intersection of memory and inflammation; (iv) RELA linking the skin-brain axis during development, DNA damage response, and pro-inflammatory control; (v) PARP1 at the crossroad of all discussed aging theories. Data points to a "burden threshold" where the beneficial regulations of distinct pathways shift toward neurotoxic activities.
神经组织因其对免疫系统的独特调节、对DNA损伤的反应、对活性氧和氮物种的耐受性以及对炎症途径的控制而引人注目。在此，我根据衰老的自由基理论、DNA损伤积累、炎症衰老以及作为程序性发育过程结果的衰老来讨论大脑衰老过程的一些独特之处。要点包括：（i）神经组织对氧化应激的恢复力；（ii）神经元修复学习诱导的DNA损伤的效率，即使其修复途径比其他细胞类型少；（iii）TLR9和NFκB在记忆与炎症的交叉点；（iv）RELA在发育、DNA损伤反应和促炎控制过程中连接皮肤-脑轴；（v）PARP1处于所有讨论的衰老理论的交叉点。数据指向一个“负担阈值”，在该阈值处，不同途径的有益调节会转向神经毒性活动。
