To inform rational therapeutics to alleviate many senescence-related diseases in terms of the pathogenic pathways, we investigated the protective mechanisms of TLH-3 against premature senescence in tert-butyl hydroperoxide (t-BHP)-induced human embryonic lung fibroblast (HELF) cells model and d-galactose-induced premature aging mice model.

We demonstrate that TLH-3 ameliorated t-BHP-induced premature senescence, which is characterized by decreased senescence-associated β-galactosidase (SA-β-Gal) positive cells containing decreased senescence effector p53 level, via up-regulating bcl-2 and down-regulated bax and caspase-3 protein expression to block t-BHP-induced inappropriate apoptosis. Furthermore, d-galactose-induced mice exhibit senescence hallmark features such as increased senescence-associated secretory phenotype characterized by increased interleukin-6 (IL-6) secretion. TLH-3 diminished age-dependent increase in circulating IL-6, lipofuscin pigment (LPF) and advanced glycation endproducts (AGEs) accumulation, the monoamine oxidase (MAO) activity and the intensity of nuclear p53 staining, which was up-regulated by d-galactose stimulation in premature aging mice. Meanwhile, TLH-3 attenuated d-galactose-induced histopathological lesions in premature aging mice.

为了告知合理的疗法以减轻许多与衰老相关的疾病的致病性途径，我们研究了TLH-3对叔丁基氢过氧化物（t- BHP）诱导的人胚肺成纤维细胞（HELF）细胞过早衰老的保护机制。小鼠模型和d-半乳糖诱导的早衰小鼠模型。

我们证明TLH-3通过上调bcl-2和bcl-2和bcl-2和bcl-2来改善t- BHP诱导的过早衰老，其特征是衰老相关的β-半乳糖苷酶（SA-β-Gal）阳性细胞减少，衰老效应因子p53水平降低。下调bax和caspase-3蛋白表达，从而阻断t-BHP诱导的不适当凋亡。此外，d-半乳糖诱导的小鼠表现出衰老标志性特征，例如以白介素6（IL-6）分泌增加为特征的衰老相关分泌表型增加。通过TLH-3减少年龄依赖性增加循环IL-6，脂褐质色素（LPF）和糖化终产物（AGEs）的积累，单胺氧化酶（MAO）活性和核的p53染色的强度，这是上调d -半乳糖刺激早衰小鼠。同时，TLH-3减轻了d-半乳糖诱导的早衰小鼠的组织病理学损害。