Insulin and aging – a disappointing relationship

Abstract

Experimental studies in animal models of aging such as nematodes, fruit flies or mice have observed that decreased levels of insulin or insulin signaling promotes longevity. In humans, hyperinsulinemia and concomitant insulin resistance are associated with an elevated risk of age-related diseases suggestive of a shortened healthspan. Age-related disorders include neurodegenerative diseases, hypertension, cardiovascular disease, and type 2 diabetes. High ambient insulin concentrations promote increased lipogenesis and fat storage, heightened protein synthesis and accumulation of non-functional polypeptides due to limited turnover capacity. Moreover, there is impaired autophagy activity, and less endothelial NO synthase activity. These changes are associated with mitochondrial dysfunction and oxidative stress. The cellular stress induced by anabolic activity of insulin initiates an adaptive response aiming at maintaining homeostasis, characterized by activation of the transcription factor Nrf2, of AMP activated kinase, and an unfolded protein response. This protective response is more potent in the long-lived human species than in short-lived models of aging research resulting in a stronger pro-aging impact of insulin in nematodes and fruit flies. In humans, resistance to insulin-induced cell stress decreases with age, because of an increase of insulin and insulin resistance levels but less Nrf2 activation. These detrimental changes might be contained by adopting a lifestyle that promotes low insulin/insulin resistance levels and enhances an adaptive response to cellular stress, as observed with dietary restriction or exercise.

Bazi Bushen ameliorates age-related energy metabolism dysregulation by targeting the IL-17/TNF inflammatory pathway associated with SASP

“…1 J). Previous studies implicate impaired lipid mobilization and increased non-adipocyte lipid synthesis in age-related fat accumulation in organs like the liver, adipose tissue, and vasculature [ 63 – 65 ]. Micro-CT and histopathological staining confirmed this lipid deposition in the visceral fat and liver of aged mice (Figs.…”

The association of metabolic syndrome with telomere length as a marker of cellular aging: a systematic review and meta-analysis

“…Insulin resistance, a hallmark of MetS, can affect telomere length through various mechanisms. Insulin resistance leads to hyperinsulinemia and increased insulin-like growth factor 1 (IGF-1) levels, which can activate signaling pathways associated with cellular proliferation and aging, potentially affecting telomere dynamics ( Kolb et al, 2023 ). MetS often involves dyslipidemia, which may contribute to telomere shortening by promoting oxidative stress, inflammation, and endothelial dysfunction, all of which impact telomere integrity ( Liu and Li, 2015 ).…”