Late-onset hypogonadism (testosterone decline with aging) and senescent cell accumulation are mutually reinforcing: SASP from senescent cells inhibits Leydig cell testosterone production via IL-6 and TNF-α, while testosterone decline removes its anti-senescence support for muscle, bone, and cardiovascular tissue. Breaking this cycle requires addressing both the hormonal (testosterone optimization) and cellular (senolytic) components.

Should men on TRT use senolytics?

Testosterone replacement therapy and senolytics are complementary — TRT restores the hormonal signal; senolytics clear the cellular dysfunction. No contraindication exists. Men on TRT may find senolytic protocols improve the cellular response to restored testosterone signaling.

What's the most important supplement for muscle aging in men over 50?

Resistance exercise remains the gold standard (3–4×/week). Among supplements: fisetin (monthly senolytic for satellite cells), creatine (supports muscle protein synthesis), and NMN (NAD+ for muscle energy metabolism) are the three most evidence-backed supplements for male muscle aging.