Dietary restriction (DR) has been used for decades to retard aging in rodents, but its mechanism of action remains an enigma. A principal roadblock has been that DR affects many different processes, making it difficult to distinguish cause and effect. To address this problem, we applied a quantitative genetics approach utilizing the ILSXISS series of mouse recombinant inbred strains. Across 42 strains, mean female lifespan ranged from 380 to 1070days on DR (fed 60% of ad libitum [AL]) and from 490 to 1020days on an AL diet.
Aging is a complex process accompanied by a decreased capacity of cells to cope with random molecular damages. Damaged proteins can form aggregates and have cytotoxic properties, a feature of many age-associated diseases. Small Hsps are chaperones involved in the refolding and/or disposal of protein aggregates. In Drosophila melanogaster, the mitochondrial DmHsp22 is preferentially upregulated during aging. Its over-expression results in an extension of lifespan (>30%) and an increased resistance to stress.
BACKGROUND: Lifespan extension is achieved through long-term application of dietary restriction (DR), and benefits of short-term dietary restriction on acute stress and inflammation have been observed. So far, the effects of short-term DR in humans are relatively unknown. We hypothesized that short-term DR in humans reduces the acute phase response following a well defined surgical trauma. METHODS: Thirty live kidney donors were randomized between 30% preoperative dietary restriction followed by 1 d of fasting (n=17) or a 4 d ad libitum regimen (n=13) prior to surgery.
Excessive production of reactive oxygen species (ROS) contributes to progression of atherosclerosis, at least in part by causing endothelial dysfunction and inflammatory activation. The class III histone deacetylase SIRT1 has been implicated in extension of lifespan. In the vasculature,SIRT1 gain-of-function using SIRT1 overexpression or activation has been shown to improve endothelial function in mice and rats via stimulation of endothelial nitric oxide (NO) synthase (eNOS). However, the effects of SIRT1 loss-of-function on the endothelium in atherosclerosis remain to be characterized.
Hormesis, the beneficial effect of a mild stress, has been proposed as a means to prolong the period of healthy ageing as it can increase the average lifespan of a cohort. However, if we want to use hormesis therapeutically it is important that the treatment is beneficial on the individual level and not just on average at the population level. Long lived lines have been shown not to benefit from a, in other lines, hormesis inducing heat treatment in Drosophila melanogaster, D. buzzatii and mice.
A commentary is offered on the chapters that comprise the section on Theoretical Foundations, emphasizing novel contributions of each. Three additional points are then made. First, while the biology of reproductive aging may be common to all human populations, its actual course can be expected to vary between individuals and between populations depending on ecological conditions and developmental histories.
Neck muscle vibration (NMV) during upright standing is known to induce forward leaning, which has been explained as a global response to the (illusory) perception of a lengthening of the dorsal neck muscles. However, the effects of NMV both at the level of individual joints and on whole-body postural coordination, and its potential modulation by vision, have not yet been analyzed in detail. Eight healthy young adult participants completed a total of ten trials each, with a 10-s period of unperturbed standing followed by a 10-s period of NMV.
Journal of Genetics and Genomics = Yi Chuan Xue Bao
CoQ is an essential electron carrier in the mitochondrial respiratory chain of both eukaryotes and prokaryotes. It consists of a benzoquinone head group and a hydrophobic polyisoprenoid tail. The genes (COQ1-9) involved in CoQ biosynthesis have been characterized in yeast. In this study, we generated and molecularly characterized a mutant allele of a novel Drosophila gene, sbo, which encodes a protein that is predicted to catalyze the prenylation of p-hydroxybenzoate with the isoprenoid chain during the process of CoQ synthesis.
The brown fat specific UnCoupling Protein 1 (UCP1) is involved in thermogenesis, a process by which energy is dissipated as heat in response to cold stress and excess of caloric intake. Thermogenesis has potential implications for body mass control and cellular fat metabolism. In fact, in humans, the variability of the UCP1 gene is associated with obesity, fat gain and metabolism. Since regulation of metabolism is one of the key-pathways in lifespan extension, we tested the possible effects of UCP1 variability on survival.
BACKGROUND: Recent studies have demonstrated that activation of autophagy increases the lifespan of organisms from yeast to flies. In contrast to the lifespan extension effect in lower organisms, it has been reported that overexpression of unc-51-like kinase 3 (ULK3), the mammalian homolog of autophagy-specific gene 1 (ATG1), induces premature senescence in human fibroblasts. Therefore, we assessed whether the activation of autophagy would genuinely induce premature senescence in human cells.