This review aims to integrate current knowledge on how mTORC1-centered metabolic and stress-response pathways regulate endometrial decidualization, cellular senescence, and receptivity, with particular emphasis on their impact on implantation in advanced maternal age and metabolic disorders. A literature search was conducted using PubMed and Google Scholar without temporal restrictions, and studies were selected according to predefined inclusion and exclusion criteria focusing on metabolic signaling and reproductive function. Physiological mTORC1 activation during the proliferative phase supports stromal cell proliferation, protein synthesis, and initiation of decidualization, while facilitating formation and clearance of physiological senescent cells. Conversely, sustained mTORC1 activation associated with aging or metabolic dysfunction enhances cellular senescence and the senescence-associated secretory phenotype (SASP) through autophagy suppression, increased oxidative stress, and DNA damage, leading to impaired decidualization and reduced endometrial receptivity. This pattern aligns with the principle of antagonistic pleiotropy, whereby traits advantageous for reproduction in youth become detrimental to tissue function later. Dysregulation of mTORC1 and its related pathways-including AMPK, Tuberous Sclerosis Complex 2 (TSC2), and the p53 axis-is linked to implantation failure, particularly in advanced maternal age, obesity, and insulin resistance. In conclusion, mTORC1-centered metabolic and stress-response networks are fundamental regulators of endometrial maturation and senescence. Incorporating the assessment of mTORC1 activity and aging-associated markers may improve endometrial evaluation and reproductive outcomes, particularly in women of advanced reproductive age. Furthermore, such approaches may also enhance diagnostic precision and potentially increase success rates in assisted reproductive technologies (ART).
