Signaling Networks Determining Life Span

Abstract

The health of an organism is orchestrated by a multitude of molecular and biochemical networks responsible for ensuring homeostasis within cells and tissues. However, upon aging, a progressive failure in the maintenance of this homeostatic balance occurs in response to a variety of endogenous and environmental stresses, allowing the accumulation of damage, the physiological decline of individual tissues, and susceptibility to diseases. What are the molecular and cellular signaling events that control the aging process and how can this knowledge help design therapeutic strategies to combat age-associated diseases? Here we provide a comprehensive overview of the evolutionarily conserved biological processes that alter the rate of aging and discuss their link to disease prevention and the extension of healthy life span.

Mitochondrial activity and dynamics changes regarding metabolism in ageing and obesity

“…Mitochondrial dysfunction is associated with the functional decline found in tissues and organs during ageing (Riera et al, 2016) and, for this reason, it has been associated with a number of age-related diseases such as neurological disorders, cardiovascularCVD, liver and kidney diseases, diabetes and cancer Wallace, 2012). Recently, a study carried out with 248 non-diabetic participants from the Baltimore Londigutinal Study of Aging has associated impaired mitochondrial capacity with greater insulin resistance (Fabbri et al, 2016).…”

Insights into mortality patterns and causes of death through a process point of view model

“…Additionally, an index of biological markers of aging was a better predictor of mortality risk than an index of activity markers (Cornman et al 2016). These studies and others suggest that, leading up to death, the dysregulation of the multiple cellular regulatory networks progresses in semi-independent patterns (Cohen 2016; Riera et al 2016). The important point for a vitality framework is the possibility of representing the distal factors of COD with separate vitality streams associated with different physiological networks.…”

Glial contributions to neuronal health and disease: new insights from Drosophila

“…It is well established that systemic insulin-like signaling pathways gradually decline with age across species (37); future work will reveal if this contributes to age-related loss of Draper/MEGF10 and attenuated glial immune responses in older animals. Interestingly, genetic deletion of insulin-like signaling pathway components, including the InR and PI3K, extends lifespan in C. elegans, Drosophila , and mammals, although increased longevity may occur at the cost of optimal metabolic fitness and overall health (38). Selected manipulation of PI3K and insulin-like cascades in a cell type specific and temporal manner may prove to be the most ideal method of optimizing glial immune gene expression and immune-like responses in the aged brain.…”