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ROLE of IGF-1 System in the Modulation of Longevity: Controversies and New Insights From a Centenarians' Perspective

igf-1 longevity

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#1 Engadin

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Posted 13 March 2019 - 05:01 PM


Human aging is currently defined as a physiological decline of biological functions in the body with a continual adaptation to internal and external damaging. The endocrine system plays a major role in orchestrating cellular interactions, metabolism, growth, and aging. Several in vivo studies from worms to mice showed that downregulated activity of the GH/IGF-1/insulin pathway could be beneficial for the extension of human life span, whereas results are contradictory in humans. In the present review, we discuss the potential role of the IGF-1 system in modulation of longevity, hypothesizing that the endocrine and metabolic adaptation observed in centenarians and in mammals during caloric restriction may be a physiological strategy for extending lifespan through a slower cell growing/metabolism, a better physiologic reserve capacity, a shift of cellular metabolism from cell proliferation to repair activities and a decrease in accumulation of senescent cells. Therefore, understanding of the link between IGF-1/insulin system and longevity may have future clinical applications in promoting healthy aging and in Rehabilitation Medicine.

 

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  Introduction

 

Aging is defined as a physiological decline of biological functions in the body with a progressive decline or loss of adaptation to internal and external damaging. In humans the aging phenotype is extremely heterogeneous and can be described as a complex mosaic resulting from the interaction of several stochastic and environmental events, genetic, and epigenetic alterations accumulated throughout the lifetime. Despite its enormous complexity, the molecular basis of aging is limited to few highly evolutionarily conserved biological mechanisms responsible for body maintenance and repair.

 

During the last 3 decades one of the most discussed topics in gerontology is the role of the growth hormone (GH)/insulin-like growth factor-1 (IGF-1)/insulin system in the regulation of longevity. Accumulating evidence suggests that this pathway plays an essential role in the pathogenesis of several age-related diseases including cancer, dementia, cardiovascular, and metabolic diseases.

 

In animal models it was shown that down-regulation of the GH/IGF-1/insulin system significantly prolongs the lifespan. However, in humans data are contradictory (56).

 

This review describes the latest advances in the research of the IGF-1 system and modulation of longevity, hypothesizing that the endocrine and metabolic adaptation observed in centenarians and in mammals during caloric restriction may be a physiological strategy for extending lifespan through a slower cell growing/metabolism, a better control in signal transmission and physiologic reserve capacity and a decrease in accumulation of senescent cells. A review of the literature was conducted using PubMed database with the following keywords: “IGF-1” or “IGF-I” and “longevity.” The search included articles published in the English language between January 2008 and August 2018.

 

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Long article. Rest here: https://www.frontier...2019.00027/full

 







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