In nonobese adults, losing and keeping off weight for two years can lower a biological age measure by 2–3 years, but regaining more than 5% of the lost weight eliminates this change.
Mechanism
Synthesis from 1 study
Eating less and losing weight lowers insulin and IGF-1, which tells your cells to slow down aging processes and repair damage better, making your biological age younger — this is shown in 10.2337/dc25-1911. But if you gain the weight back, your body produces more insulin and IGF-1 again, turning...
Most probable mechanism
When people eat fewer calories and lose weight, their bodies produce less insulin and IGF-1, which tells cells to slow down growth and repair processes, leading to a younger biological age. But if they regain the weight, fat tissue comes back and causes insulin and IGF-1 levels to rise again, turning on growth pathways that speed up aging. This is backed by evidence from 10.2337/dc25-1911 showing that keeping weight off keeps insulin and IGF-1 low, while regaining weight brings them back up and erases the anti-aging benefits.
Caloric restriction reduces nutrient availability, decreasing insulin secretion from pancreatic β-cells — supported by 10.2337/dc25-1911
Lower insulin levels increase hepatic production of IGFBP-1, reducing free IGF-1 bioavailability — supported by 10.2337/dc25-1911
Reduced insulin and IGF-1 signaling downregulates the PI3K/AKT/mTOR nutrient-sensing pathway, suppressing cellular proliferation and enhancing autophagy and DNA repair — supported by 10.2337/dc25-1911
Sustained suppression of mTOR signaling reduces the rate of molecular damage accumulation, leading to a measurable decline in biological age via the Klemera-Doubal method — supported by 10.2337/dc25-1911
Weight regain restores adipose tissue mass, triggering hyperleptinemia and leptin resistance, which promotes hyperphagia and positive energy balance — supported by 10.2337/dc25-1911
Persistent positive energy balance reactivates insulin secretion and IGF-1 bioavailability, reactivating mTOR signaling and suppressing autophagy — supported by 10.2337/dc25-1911
Reactivation of insulin-IGF-1/mTOR signaling accelerates molecular aging processes, abolishing the reduction in biological age measured by the Klemera-Doubal method — supported by 10.2337/dc25-1911
Evidence from Studies
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