Senotherapeutic approach to age-related endocrine diseases.

Abstract

Senescent cells progressively accumulate in the endocrine glands and their target tissue during the biological aging process. Senescence leads to hormonal imbalances contributing to various age-related endocrine diseases (AREDs). Cellular senescence, characterized by irreversible cell-cycle arrest, becomes more prevalent in advanced age, and the senescent cells release pro-inflammatory and pro-fibrotic factors, exacerbating endocrine dysregulation. Senescence-associated secretory phenotype (SASP) contributes to the pathogenesis of AREDs such as metabolic syndrome, sarcopenia, osteoporosis, and type 2 diabetes mellitus. Impaired metabolism of melatonin, cortisol, insulin, growth, and thyroid hormones are all intimately linked to age-related hormonal imbalance and dysregulated circadian rhythms. Pharmacokinetic and pharmacodynamic processes are also known to be impacted by circadian oscillations, which can also impact the toxicity and effectiveness of several therapeutic agents. Diagnosing and monitoring AREDs requires an assessment of individual circadian oscillations, inappropriate polypharmacy, and the senotherapeutic benefits of routine medications in the elderly. Hormone-oriented senotherapeutic strategies combined with anti-inflammatory SASP-related treatments may alleviate the detrimental effects of ARED symptoms. However, the complexity of senotherapy and the risk of possible adverse effects necessitate personalized treatment approaches.