Moreira-Pais Alexandra, Ferreira Rita, Aires Inês, Sousa-Mendes Cláudia, Nogueira-Ferreira Rita, Seixas Fernanda, Leite-Moreira Adelino, Oliveira Paula A, Duarte José A
Research Center in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sports, University of Porto (FADEUP) and Laboratory for Integrative and Translational Research in Population Health (ITR), 4200-450, Porto, Portugal.
LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.
Biogerontology. 2025 Jan 24;26(1):47. doi: 10.1007/s10522-024-10182-y.
Sarcopenia and cancer cachexia are two life-threatening conditions often misdiagnosed. The skeletal muscle is one of the organs most adversely affected by these conditions, culminating in poor quality of life and premature mortality. In addition, it has been suggested that chemotherapeutic agents exacerbate cancer cachexia, as is the case of doxorubicin. Herein, we sought to investigate markers of inflammation and neuromuscular junction (NMJ) remodeling during aging and in response to cancer or cancer with chemotherapy. To address this, we utilized female rats across three age groups - young, adult, and old - to examine age-related changes, with old rats serving as a sarcopenia model. Additionally, a chemically-induced breast cancer (BCa) model was implemented in female adult rats, both without (adult BCa) or with doxorubicin administration (adult BCaDOX), to study cancer cachexia. The atrophy of the gastrocnemius muscle was observed in old, adult BCa and adult BCaDOX rats compared to adult ones. No signs of inflammation or NMJ impairment were observed in adult BCa or adult BCaDOX rats, except for the low levels of the subunit α1 of the acetylcholine receptor in adult BCaDOX rats compared to adult ones. In contrast, old rats presented high serum levels of interleukin 6, brain-derived neurotrophic factor (BDNF) and calcitonin gene-related peptide compared to young rats. In the gastrocnemius muscle, BDNF levels were decreased in old rats compared to adult rats, suggesting impaired skeletal muscle regeneration upon age-induced damage. The BDNF muscle levels were inversely correlated with its levels in circulation in adult and old rats. Hence, this work highlights BDNF as a specific biomarker of age-induced skeletal muscle atrophy, at least, in the differential diagnosis against cancer- or cancer with chemotherapy-induced muscle wasting.
肌肉减少症和癌症恶病质是两种常被误诊的危及生命的病症。骨骼肌是受这些病症影响最严重的器官之一，最终导致生活质量下降和过早死亡。此外，有人提出化疗药物会加重癌症恶病质，比如阿霉素就是这种情况。在此，我们试图研究衰老过程中以及对癌症或癌症化疗反应时炎症和神经肌肉接头（NMJ）重塑的标志物。为解决这个问题，我们使用了三个年龄组的雌性大鼠——年轻、成年和老年——来检查与年龄相关的变化，老年大鼠作为肌肉减少症模型。此外，在成年雌性大鼠中建立了化学诱导的乳腺癌（BCa）模型，一组不给予阿霉素（成年BCa组），另一组给予阿霉素（成年BCaDOX组），以研究癌症恶病质。与成年大鼠相比，老年、成年BCa组和成年BCaDOX组大鼠的腓肠肌出现萎缩。在成年BCa组或成年BCaDOX组大鼠中未观察到炎症或NMJ损伤的迹象，只是成年BCaDOX组大鼠与成年大鼠相比，乙酰胆碱受体α1亚基水平较低。相比之下，与年轻大鼠相比，老年大鼠血清白细胞介素6、脑源性神经营养因子（BDNF）和降钙素基因相关肽水平较高。在腓肠肌中，与成年大鼠相比，老年大鼠的BDNF水平降低，这表明年龄诱导损伤后骨骼肌再生受损。成年和老年大鼠肌肉中的BDNF水平与其循环中的水平呈负相关。因此，这项研究强调BDNF至少是年龄诱导的骨骼肌萎缩的一种特异性生物标志物，可用于与癌症或癌症化疗诱导的肌肉萎缩进行鉴别诊断。
