A team of metabolic health researchers demonstrates that daily cold exposure inducing shivering activates hormetic pathways—enhancing autophagy, brown fat thermogenesis, and glucose metabolism—to improve metabolic markers and cellular resilience for longevity.

Key points

• Full-body cooling suit at 10 °C for 1 hr/day over 10 days induces shivering, increasing energy expenditure by ~50% and improving glucose tolerance by 6–11%.
• Daily 14 °C cold-water immersion for 7 days enhances autophagy markers (↑LC3-II, ↓p62) and reduces apoptosis (caspase-3) in skeletal muscle biopsies.
• Cold acclimation lowers inflammatory cytokines (TNF-α, IL-6) in immune cells and decreases blood pressure by ~10/7 mmHg, indicating systemic metabolic and vascular benefits.

Why it matters: These findings highlight cold-induced shivering as a non-pharmacological hormetic stimulus that enhances metabolic health and cellular repair pathways.

Researchers at Healthspan Medical unveiled how SGLT-2 inhibitors, originally developed to lower blood sugar, emulate the metabolic effects of caloric restriction by promoting urinary glucose excretion. This mild energy deficit activates longevity pathways—AMPK, SIRT1—while suppressing mTOR and insulin/IGF-1 signaling, thereby enhancing autophagy, mitochondrial function, and metabolic flexibility. The pharmacological approach offers a practical alternative to strict dietary interventions for promoting healthier cellular aging.

Key points

• SGLT-2 inhibitors induce mild glucosuria (~60–80 g/day), mimicking a continuous fasting state
• Activated AMPK and SIRT1 pathways enhance fatty acid oxidation, mitochondrial biogenesis, and cellular repair
• Inhibited mTOR and reduced insulin/IGF-1 signaling promote autophagy and reduce pro-growth signaling
• Empagliflozin demonstrated reduced hepatic steatosis, lowered pro-inflammatory M1 macrophages, and increased UCP1 expression in HFD-fed mice
• Early human data show weight loss, improved insulin sensitivity, and cardiometabolic risk-factor reduction

Why it matters: By replicating the cellular effects of caloric restriction without severe dietary changes, SGLT-2 inhibitors may shift the aging paradigm toward pharmacological metabolic reprogramming. This approach could provide a scalable therapy to enhance healthspan, mitigate age-related diseases, and overcome adherence barriers associated with traditional fasting or caloric restriction regimens.

In new research from Healthspan, canagliflozin, an SGLT2 inhibitor, indirectly clears senescent cells by activating AMPK and reducing PD-L1. This metabolic reset, evident in markers of aging, suggests benefits against obesity and cardiovascular decline. Consider these insights for refining anti-aging protocols.