马歇尔大学的Eric Blough及其同事发现，常用的止痛药乙酰氨基酚或许能够防止因衰老引起的肌肉损失。

蛋白激酶B在调节细胞的生长，增殖以及代谢的生物过程中具有重要作用，该课题组研究了乙酰氨基酚如何影响蛋白激酶B  (Akt)的调节作用。

研究数据表明，骨骼肌在衰老过程中，发挥某些功能的酶会逐渐减少，而乙酰氨基酚能使老龄动物的Akt活性水平恢复到与年轻动物相同的水平。Akt活性的提高反过来也能影响肌肉细胞的大小，并降低肌肉细胞的死亡。

该研究报告发表在7月29日PLoS ONE杂志上，首次研究了动物摄入乙酰氨基酚，能够用于治疗衰老引起的肌肉损失。

据研究人员Miaozong Wu介绍，乙酰氨基酚在体内能够降低活性氧的含量，若体内聚集大量的活性氧将引起多种衰老相关的疾病，因此，该研究或许可以为减缓衰老提供新的途径。

PLoS ONE 4(7): e6430. doi:10.1371/journal.pone.0006430

Aging-Associated Dysfunction of Akt/Protein Kinase B: S-Nitrosylation and Acetaminophen Intervention

Miaozong Wu1,2, Anjaiah Katta3, Murali K. Gadde1,2, Hua Liu1,2,5, Sunil K. Kakarla3, Jacqueline Fannin3, Satyanarayana Paturi1,2, Ravi K. Arvapalli1,2, Kevin M. Rice1,2,4, Yeling Wang1,2,6, Eric R. Blough1,2,3,4*

1 Department of Biological Sciences, Marshall University, Huntington, West Virginia, United States of America, 2 Cell Differentiation and Development Center, Marshall University, Huntington, West Virginia, United States of America, 3 Department of Pharmacology, Physiology and Toxicology, Marshall University, Huntington, West Virginia, United States of America, 4 Department of Exercise Science, Sport and Recreation, Marshall University, Huntington, West Virginia, United States of America, 5 Department of Physiology and Pharmacology, Southeast University, Nanjing, China, 6 The First Hospital, Jilin University, Jilin, China

Background

Aged skeletal muscle is characterized by an increased incidence of metabolic and functional disorders, which if allowed to proceed unchecked can lead to increased morbidity and mortality. The mechanism(s) underlying the development of these disorders in aging skeletal muscle are not well understood. Protein kinase B (Akt/PKB) is an important regulator of cellular metabolism and survival, but it is unclear if aged muscle exhibits alterations in Akt function. Here we report a novel dysfunction of Akt in aging muscle, which may relate to S-nitrosylation and can be prevented by acetaminophen intervention.

Principal Findings

Compared to 6- and 27-month rats, the phosphorylation of Akt (Ser473 and Thr308) was higher in soleus muscles of very aged rats (33-months). Paradoxically, these increases in Akt phosphorylation were associated with diminished mammalian target of rapamycin (mTOR) phosphorylation, along with decreased levels of insulin receptor beta (IR-β), phosphoinositide 3-kinase (PI3K), phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and phosphorylation of phosphoinositide-dependent kinase-1 (PDK1) (Ser241). In vitro Akt kinase measurements and ex vivo muscle incubation experiments demonstrated age-related impairments of Akt kinase activity, which were associated with increases in Akt S-nitrosylation and inducible nitric oxide synthase (iNOS). Impairments in Akt function occurred parallel to increases in myocyte apoptosis and decreases in myocyte size and the expression of myosin and actin. These age-related disorders were attenuated by treating aged (27-month) animals with acetaminophen (30 mg/kg body weight/day) for 6-months.

Conclusions

These data demonstrate that Akt dysfunction and increased S-nitrosylation of Akt may contribute to age-associated disorders in skeletal muscle and that acetaminophen may be efficacious for the treatment of age-related muscle dysfunction.