Healthy Aging – Insights from Drosophila

Abstract

Human life expectancy has nearly doubled in the past century due, in part, to social and economic development, and a wide range of new medical technologies and treatments. As the number of elderly increase it becomes of vital importance to understand what factors contribute to healthy aging. Human longevity is a complex process that is affected by both environmental and genetic factors and interactions between them. Unfortunately, it is currently difficult to identify the role of genetic components in human longevity. In contrast, model organisms such as C. elegans, Drosophila, and rodents have facilitated the search for specific genes that affect lifespan. Experimental evidence obtained from studies in model organisms suggests that mutations in a single gene may increase longevity and delay the onset of age-related symptoms including motor impairments, sexual and reproductive and immune dysfunction, cardiovascular disease, and cognitive decline. Furthermore, the high degree of conservation between diverse species in the genes and pathways that regulate longevity suggests that work in model organisms can both expand our theoretical knowledge of aging and perhaps provide new therapeutic targets for the treatment of age-related disorders.

Blocking IGF Signaling in Adult Neurons Alleviates Alzheimer's Disease Pathology through Amyloid-β Clearance

“…Insulinlike growth factor I (IGF-I), through its cognate receptor IGF-1R and downstream effectors, controls stress resistance, aging, and lifespan . Since aging is modulated by insulin-like signals in the brain (Taguchi et al, 2007;Kappeler et al, 2008;, this pathway could function as a molecular bridge between physiological aging and AD pathogenesis (Carro et al, 2002). In accord with that, constitutive heterozygous knock-out of IGF-1R in an APP/PS1 AD mouse model reduces astrogliosis, prevents neuronal death, and alleviates ADassociated cognitive deficits (Cohen et al, 2009).…”

“…Since aging is modulated by insulin-like signals in the brain (Taguchi et al, 2007;Kappeler et al, 2008;, this pathway could function as a molecular bridge between physiological aging and AD pathogenesis (Carro et al, 2002). In accord with that, constitutive heterozygous knock-out of IGF-1R in an APP/PS1 AD mouse model reduces astrogliosis, prevents neuronal death, and alleviates ADassociated cognitive deficits (Cohen et al, 2009). However, that model could not distinguish between benefits due to delayed aging in long-lived IGF-1R ϩ/Ϫ mutants and brain-specific mechanisms.…”

Long-term dietary exposure to low concentration of dichloroacetic acid promoted longevity and attenuated cellular and functional declines in aged Drosophila melanogaster

“…Relevant to the higher mammals, Drosophila exhibits an age-related decline in several behaviors such as senescence of motor activity, olfaction, olfactory memory, and noncircadian rest (Grotewiel et al 2005). Assay for locomotor performance is one of the reliable assays to examine the senescence of motor activity in flies (Lliadi et al 2012). Further, this model has been a key to comprehend the association between hsps and aging process since the discovery of heat shock response and hsps (Tower 2011).…”

Isolating Intestinal Stem Cells from Adult <em>Drosophila</em> Midguts by FACS to Study Stem Cell Behavior During Aging

“…Drosophila melanogaster is a highly suitable model organism to study aging since it has a short lifespan (about 60-70 days) and exhibits aging phenotypes (reviewed in 4 ). Moreover, the aging process in Drosophila can be accelerated by temperature.…”