A new framework expands the classic 12 hallmarks of aging to 14, classifying them into three tiers: primary (root causes like genomic instability, telomere shortening, epigenetic alterations, loss of proteostasis, impaired macroautophagy), antagonistic (stress responses such as mitochondrial dysfunction, cellular senescence, deregulated nutrient sensing), and integrative (observable consequences like chronic inflammation, stem cell exhaustion, altered intercellular communication, extracellular matrix changes, dysbiosis, and psychosocial isolation).
Women’s ovarian health—in cases of premature ovarian insufficiency (POI) or natural menopause—is tightly linked to antagonistic hallmarks: for instance, mitochondrial damage reduces energy in follicles, cellular senescence creates inflammation and tissue damage, and deregulated nutrient sensing (via AMPK/mTOR/sirtuin pathways) impairs metabolic support to the ovary. The article suggests five nutrients showing promise for mitigating ovarian aging: fisetin (a senolytic), PQQ (promotes mitochondrial biogenesis), S-equol (plant-estrogen modulator), L-5-Methyltetrahydrofolate Calcium (for epigenetic support), and Reishi mushroom extract (immune and hormonal modulator).
