年龄和性别影响了对他类药物治疗的转录组反应,这些药物在系统代谢功能障碍期间控制肝脏衰老
David S Umbaugh1, Liuyang Wang1,2, Kuo Du1
1Departments of Medicine.
Hepatology (Baltimore, Md.)
|February 2, 2026
概括
通过抑制衰老和促进铁亡,他类药物可能会减缓代谢功能障碍相关的脂肪性肝病 (MASLD) 的生物衰老. 这项研究显示,他类药物的使用对MASLD患者的肝脏衰老途径产生影响.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 老年学是一门学科.
- 分子生物学分子生物学
背景情况:
- 高龄是代谢功能障碍相关的脂肪性肝病 (MASLD) 的风险因素.
- 衰老对MASLD疗法和生物衰老调节剂的影响尚不清楚.
- 用于心血管疾病的他类药物在衰老的人类肝脏中具有定义不佳的分子效应.
研究的目的:
- 调查MASLD中对治疗的年龄相关反应.
- 确定疗法如何影响生物衰老调节器.
- 阐明他类药物在老化的人类肝脏中的分子作用.
主要方法:
- 对肝脏转录组和368名MASLD患者的临床数据的分析.
- 专注于年龄相关的反应和衰老 - 铁亡的相互作用.
- 在一个独立的肥胖群体中验证.
主要成果:
- 静止剂使用者表现出较低的ALT,AST和LDL胆固醇,尤其是老年人.
- 类固醇使用抑制了与衰老相关的途径和增加了与铁死相关的途径.
- 这些发现在倾向性得分匹配后和在独立队列中一致.
结论:
- 肝脏转录重塑在MASLD中不同于他类药物使用者和非使用者.
- 类他类药物抑制衰老路径,并诱导肝脏中的铁亡路径.
- 通过作为老化剂,他类药物可以减轻MASLD中的生物衰老.
相关概念视频
Aging
703
Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
703
Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Metabolism
215
Geriatric patients show significant variation in how their bodies process medications, which can change how effective and safe treatments are. The liver is the primary organ where drug metabolism occurs, involving two main types of chemical reactions: phase I and II. Phase I metabolism is driven by the cytochrome P450 enzyme system, which includes key types such as CYP3A, CYP2D6, and CYP2C9. Research indicates that while aging doesn't notably alter the levels or activity of these enzymes, it...
215
The Effect of Aging on Tissues
3.5K
Several body functions deteriorate with age. The external signs of aging are easily identifiable. For example, the skin becomes dry, less elastic, and thins out, forming wrinkles. The skin of the face begins to appear looser due to a decrease in the levels of elastic and collagen fibers in the connective tissue. Additionally, melanin production in the hair follicle decreases with age, resulting in gray hair. Moreover, the senses of sight and hearing decline, so glasses and hearing aids may...
3.5K
Changes in the Appendicular Skeleton with Age
3.5K
The upper and lower limb initially develops as a small bulge called a limb bud, which appears on the lateral side of the early embryo. The upper limb bud appears near the end of the fourth week of development, with the lower limb bud appearing shortly after.
Initially, the limb buds consist of a core of mesenchyme covered by a layer of ectoderm. The ectoderm at the end of the limb bud thickens to form a narrow crest called the apical ectodermal ridge. This ridge stimulates the underlying...
Initially, the limb buds consist of a core of mesenchyme covered by a layer of ectoderm. The ectoderm at the end of the limb bud thickens to form a narrow crest called the apical ectodermal ridge. This ridge stimulates the underlying...
3.5K
Control Systems
1.9K
Control systems are everywhere in contemporary society, influencing diverse applications from aerospace to automated manufacturing. These systems can be found naturally within biological processes, such as blood sugar regulation and heart rate adjustment in response to stress, as well as in man-made systems like elevators and automated vehicles. A control system is essentially a network of subsystems and processes that collaboratively convert specific inputs into desired outputs.
At the heart...
At the heart...
1.9K
Pharmacodynamics in Geriatric Patients: Effects of Age
237
Age-related pharmacokinetic changes are extensively documented, but understanding age-related pharmacodynamic alterations is relatively limited. This knowledge gap can be partly attributed to the complexity of developing appropriate measures of drug responses compared to bioanalytical methods for determining drug concentrations.Most information regarding age-related differences in human pharmacodynamics originates from cross-sectional studies. However, these studies assume that observed mean...
237


