The Antagonistic Pleiotropy of IGF-1 Signaling in Aging – Innovita Research

IGF-1 is one of the better studied areas of metabolism relevant to determining the pace of aging in a species, involved in the regulation of tradeoffs between growth and sustained function. In the context of the evolution of aging, a mechanism exhibiting antagonistic pleiotropy is beneficial in youth but harmful in later life.

Natural selection acts more strongly on features of a youthful individual, favoring those more capable of reproducing prior to mortality via predation and disease. Features are selected on the basis of early life success with litter regard for whether or not they are sustainable. Thus we wind up with a world in which near all species have a biochemistry that is set up for a fast start to life, and then runs awry and degenerates with the passage of time.

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While insulin-like growth factor-1 (IGF-1) is a well-established modulator of aging and longevity in model organisms, its role in humans has been controversial. In this study, we used the UK Biobank (n = 440,185) to resolve previous ambiguities in the relationship between serum IGF-1 levels and clinical disease. We examined prospective associations of serum IGF-1 with mortality, dementia, vascular disease, diabetes, osteoporosis, and cancer, finding two generalized patterns.

First, IGF-1 interacts with age to modify risk in a manner consistent with antagonistic pleiotropy; younger individuals with high IGF-1 are protected from disease, while older individuals with high IGF-1 are at increased risk for incident disease or death. Second, the association between IGF-1 and risk is generally U-shaped, indicating that both high and low levels of IGF-1 may be detrimental.

With the exception of a more uniformly positive relationship between IGF-1 and cancer, these effects were remarkably consistent across a wide range of conditions, providing evidence for a unifying pathway that determines risk for most age-associated diseases. These data suggest that IGF-1 signaling could be harmful in older adults, who may actually benefit from the attenuation of biological growth pathways.


Source: Fight Aging!