Research
Hormonal
Inhibition of the Insulin/IGF-1 Signaling (IIS) pathway extends lifespan in multiple species by enhancing mitochondrial function, biogenesis, and mitophagy.
Genetic variants that naturally result in lower IGF-1 levels are associated with human longevity. While not a direct prescription, this suggests that the hormonal environment of reduced growth signaling may be protective against aging, distinct from the muscle-building goals of high IGF-1 in youth.
GoodSupportsHIGH confidence
inhibition of IIS signaling can delay aging even when applied in advanced age... IIS inhibition appears to influence mitochondrial bioenergetics and biogenesis by reducing the half-life of mitochondrial proteins and by enhancing the expression of the nuclear encoded mitochondrial genes.
Why this rating
Strong evidence from multiple model organisms (yeast, worms, flies, mice) and some human genetic data.
Source
Mitochondria in the signaling pathways that control longevity and health span
Mansour Akbari et al. · Ageing Research Reviews · 2019
DOI 10.1016/j.arr.2019.100940
narrative_reviewCited 207×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Inhibition of mTORC1 by rapamycin extends lifespan in multiple species by enhancing autophagy and mitophagy, thereby maintaining mitochondrial homeostasis.Good
- Activation of AMPK by dietary restriction or compounds like metformin extends lifespan by inhibiting mTOR and promoting mitochondrial biogenesis.Good
- Mild mitochondrial stress and modest increases in mitochondrial ROS levels increase lifespan in C. elegans, demonstrating that ROS acts as a beneficial signaling molecule rather than solely as a damaging agent.Moderate
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
This is one finding among thousands. Every one is graded and traced to its source, so you can see what the evidence actually supports. Browse the research →