In animal models the relationship is clear: less insulin signalling extends life. In humans there are biologically plausible mechanisms and indications that chronically high insulin signalling accelerates ageing, but evidence that actively intervening in this pathway actually makes people live longer is still lacking. Improving insulin sensitivity through exercise and diet is well supported as a strategy against age-related diseases, even though a direct lifespan benefit in humans has not been demonstrated.
In worms and fruit flies the link between insulin signalling and ageing is rock solid: when the gene encoding the insulin receptor (daf-2) is less active in the roundworm C. elegans, lifespan doubles or more. This is one of the most reproducible findings in the entire field of ageing research. Researchers in fruit flies consistently observe the same outcome. These are explicitly laboratory animals, but the proteins involved closely resemble those found in humans.
In mice there is comparable evidence, though it is less strong than in invertebrates. Mice in which the insulin receptor was switched off exclusively in fat cells lived longer than normal mice. Mice with low growth hormone and consequently low insulin levels and higher insulin sensitivity also lived notably longer. This suggests that in mammals too, the level of insulin signalling partly determines the pace of ageing.
An important mechanism behind this effect is a group of proteins known as FOXO proteins. Insulin actively suppresses these proteins. When insulin signalling is low, FOXO proteins are free to drive processes such as cell repair and stress resistance. These FOXO proteins are found from worm to human, which underscores their evolutionary relevance. Chronically elevated insulin signalling suppresses FOXO proteins and can thereby slow down protective processes within the cell.
The relationship between insulin and ageing also works in the other direction. The ageing process itself impairs insulin function: the pancreas produces less insulin, the body breaks down insulin less efficiently, and tissues become less sensitive to insulin. This declining insulin sensitivity increases the risk of type 2 diabetes, heart disease and possibly also brain conditions such as Alzheimer's disease at older ages.
A large comparative study across five species simultaneously, including humans, showed that ageing is accompanied by an acceleration in the rate at which cells translate genetic information into proteins. That acceleration is associated with more errors. Both reduced insulin/IGF-1 signalling and eating less reversed most of these harmful molecular changes. This points to a fundamental mechanism by which insulin partly governs the pace of ageing, although a proven human benefit from intervening in this pathway has not yet been demonstrated.
For people with insulin-dependent diabetes, the practical side of insulin treatment at an advanced age is a separate safety concern. They need insulin to survive, but daily injections can become harder to manage in old age due to reduced cognitive function or limited motor skills. As for actively improving insulin sensitivity as a life-extending measure in humans, this cannot be concretely quantified from the available studies; the evidence so far comes primarily from animal and laboratory research.
Based on animal studies (C. elegans, fruit flies, mice, rats) and one large cross-species study that also included human tissue. Direct evidence for lifespan extension through intervention in insulin signalling in healthy humans is lacking. Associative human data point to the role of insulin resistance in age-related diseases.