Age-related mTOR in gynaecological cancers

Aging is an uninvited sequel of organismal growth and the ultimacy of which is death. At the molecular level, organismal aging is a conversion from cellular quiescence to senescence state. Age is a major risk factor for many diseases including diabetes, obesity, neurodegenerative disorders, and cancer. Other consequences of aging are not defined by diseases, but rather considered ‘stages of life’, because they normally occur in everyone, such as menopause in females. However, deregulated female reproductive cycles (early menarche and/or late menopause) lead to hormonal imbalance and cancer at later stages of life. Endometrial and ovarian cancers are the most frequently diagnosed cancers in aged women and account for significant mortality. The incidence of both these cancer increases with advancing age, peaking around 60 to 70 years of age [1, 2]. Up to 80% of such patients are found to have genetic aberrations in the members of the PI3K-mTOR (phosphoinositide 3kinase-mammalian target of rapamycin) pathway [3, 4]. mTOR signaling is important in regulating the cell cycle of the majority of proliferating cells, where homeostasis is maintained by either cell division or quiescence [5]. In contrast, hyperactive mTOR signaling causes cellular hypertrophy, which alters homeostasis, leading to cellular senescence, cancer and age-related diseases [5].