Aging and estrogen deprivation, particularly in postmenopausal women, significantly increase the risk of cardiovascular diseases by driving metabolic and mitochondrial dysfunctions. Although estrogen replacement therapy is cardioprotective, its long-term risks are significant. Spermidine, a natural polyamine, is known for its longevity and cardioprotective effects, but its efficacy in models combining accelerated aging-like model and estrogen deprivation is unclear. Seventy female Wistar rats were separated into sham and ovariectomy (OVX) groups. After twelve weeks, sham-operated rats were divided into three groups and treated with distilled water (Sham-V; p.o.), D-galactose (Sham-D; 150 mg/kg/day; s.c.), and spermidine (Sham-DS; 20 mg/kg/day; p.o.) for eight weeks. After ovariectomy, the OVX-operated rats were given D-galactose for 12 weeks to accelerated aging-like model, and were subdivided into four groups and treated with distilled water (OVX-D; p.o.), spermidine (OVX-DS; 20 mg/kg/day; p.o.), sesame oil (OVX-DO; estrogen vehicle; s.c.), and estrogen (OVX-DE; estradiol; 50 µg/kg/day; s.c.) for eight weeks. Rats in both accelerated aging-like model and estrogen deprivation groups developed cardiometabolic dysfunction indicated by dyslipidemia, insulin resistance, mitochondrial dysfunction, impaired mitophagy, and apoptosis. Spermidine significantly improved these adverse effects, comparable to estrogen, without altering cardiac senescence and insulin resistance. Spermidine could serve as a potential therapeutic strategy for mitigating cardiometabolic complications in postmenopausal populations.
Kaorop et al. (Sun,) studied this question.