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Lower IGF-1 Correlates with Better Cognition in Elderly Women


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Posted 25 October 2016 - 11:11 AM


Researchers have for some years now studied the biochemistry and genetics of exceptional human longevity in a long-lived population of Ashkenazi Jews. In the recent paper noted here, the authors find an association between IGF-1, which is well-studied in the context of aging and natural variations in life span, and cognitive ability in the elderly. In this context, it is interesting to look back at the results of past studies on IGF-1, such as the demonstration that lower levels predict survival in women only, and observations of increased mouse life span due to lowered IGF-1. If you want to lower IGF-1 yourself, the best way to go about it is to practice calorie restriction for the long-term. Calorie restriction is known to improve health and longevity in a range of species, though it is far from clear as to how much of its effects are driven by IGF-1 levels.

Cognitive decline is a highly prevalent condition among the aging population that causes significant morbidity in the elderly and results in rising expense for the healthcare system. Although aging is a major risk factor for cognitive impairment, some individuals with exceptional longevity demonstrate delayed onset of dementia by as much as 13 years, with many not manifesting it at all. The fact that individuals with exceptional longevity possess factors that allow them to delay or avoid age related diseases make them a particularly attractive model for the study of healthy aging. One of the features identified in individuals with exceptional longevity was partial resistance to insulin-like growth factor-1 (IGF-I) resulting from a mutation in the IGF-I receptor gene. Subsequent studies have shown that lower IGF-I and IGF-I/IGF binding protein-3 (IGFBP-3) ratio are associated with extended survival in nonagenarians and better performance at activities of daily living.

Despite evidence from humans and experimental models that reduced circulating IGF-I may promote longevity and healthy lifespan, the role of peripheral IGF-I in cognition and muscle function remains unresolved. Several cross-sectional and prospective studies linked lower IGF-I to poorer cognitive function, as well as higher risk for mild cognitive impairment and Alzheimer's disease. On the other hand, a recent prospective study in older men associated IGF-I levels in the lowest quintile with less cognitive decline. Adding to this debate are the differences observed between the sexes. For example, in the Rancho-Bernardo cohort higher IGF-I was associated with better cognitive function only among men, but not women. With the understanding that healthspan extension is an important determinant of healthy aging, we set out to test the hypothesis that individuals with exceptional longevity and low circulating IGF-I levels not only exhibit extended survival, but are also healthier in cognitive and muscle function domains. Furthermore, given our prior findings that low IGF-I benefited females preferentially, we tested whether this association is sex-specific in relation to these other clinical outcomes.

IGF-I levels and cognitive assessment were available for 203 participants, 163 female and 40 male, median age 97.2 years and 97.5 years, respectively. Measured levels of IGF-I were not found to be significantly different between males and females; however, the IGF-I/IGFBP-3 ratio was significantly lower in females compared to males. Lower serum IGF-I levels were found to be associated with better cognitive function in females with exceptional longevity, but not in males. Furthermore, no detriment to muscle mass or function was observed in this cohort among women or men with IGF-I levels within the lowest tertile of IGF-I compared to individuals with IGF-I in the upper two tertiles. Our study is the first to demonstrate a gender specific negative association between IGF-I and cognition in the extremely elderly. This supports previous data showing that lower IGF-I may have protective effects in aging that may be gender specific. No association was found between tertiles of circulating IGF-I and muscle mass or muscle function in our cohorts. These results suggest that circulating IGF-I plays a minimal role in maintaining muscle mass or strength in individuals with exceptional longevity.

Link: http://dx.doi.org/10...32/aging.101063


View the full article at FightAging




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