This past decade has seen the identification of numerous conserved genes that extend lifespan in diverse species, yet the number of compounds that extend lifespan is relatively small. A class of compounds called STACs, which were identified as activators of Sir2/SIRT1 NAD+-dependent deacetylases, extend the lifespans of multiple species in a Sir2-dependent manner and can delay the onset of age-related diseases such as cancer, diabetes and neurodegeneration in model organisms.
Calorie restriction (CR) is a non-genetic manipulation that reliably results in extended lifespan of several species ranging from yeast to dogs. The lifespan extension effect of CR has been strongly associated with an increased level and activation of the silent information regulator 2 (Sir2) histone deacetylase and its mammalian ortholog Sirt1. This association led to the search for potential Sirt1-activating, life-extending molecules. This review briefly outlines the experimental findings on resveratrol and other dietary activators of Sirt1.
The absence of mtDNA in rho0 yeast cells affects both respiration and mitochondrial-nuclear communication (e.g., retrograde regulation, intergenomic signaling, or pleiotropic drug resistance). Previously, it has been reported that some rho0 strains have increased replicative lifespans, attributable to the lack of respiration and retrograde regulation.
This annual review focuses on invertebrate model organisms, which shed light on new mechanisms in aging and provide excellent systems for both genome-wide and in-depth analysis. This year, protein interaction networks have been used in a new bioinformatic approach to identify novel genes that extend replicative lifespan in yeast. In an extended approach, using a new, human protein interaction network, information from the invertebrates was used to identify new, candidate genes for lifespan extension and their orthologues were validated in the nematode Caenorhabditis elegans.
Epidemiological studies propose that extension of the human lifespan or the reduction of age associated diseases may be achieved by physical exercise, caloric restriction, and by consumption of certain substances such as resveratrol, selenium, flavonoids, zinc, omega 3 unsaturated fatty acids, vitamins E and C, Ginkgobiloba extracts, aspirin, green tea catechins, antioxidants in general, and even by light caffeine or alcohol consumption. Though intriguing, these studies only show correlative (not causative) effects between the application of the particular substance and longevity.
Although autophagy has widely been conceived as a self-destructive mechanism that causes cell death, accumulating evidence suggests that autophagy usually mediates cytoprotection, thereby avoiding the apoptotic or necrotic demise of stressed cells. Recent evidence produced by our groups demonstrates that autophagy is also involved in pharmacological manipulations that increase longevity. Exogenous supply of the polyamine spermidine can prolong the lifespan of (while inducing autophagy in) yeast, nematodes and flies.
Dietary restriction (DR) delays or prevents age-related diseases and extends lifespan in species ranging from yeast to primates. Although the applicability of this regimen to humans remains uncertain, a proportional response would add more healthy years to the average life than even a cure for cancer or heart disease. Because it is unlikely that many would be willing or able to maintain a DR lifestyle, there has been intense interest in mimicking its beneficial effects on health, and potentially longevity, with drugs.
To identify new genetic regulators of cellular aging and senescence, we performed genome-wide comparative RNA profiling with selected human cellular model systems, reflecting replicative senescence, stress-induced premature senescence, and distinct other forms of cellular aging. Gene expression profiles were measured, analyzed, and entered into a newly generated database referred to as the GiSAO database.
Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Studies in invertebrate model organisms have led to a wealth of knowledge concerning the ageing process. But which of these discoveries will apply to ageing in humans? Recently, an assessment of the degree of conservation of ageing pathways between two of the leading invertebrate model organisms, Saccharomyces cerevisiae and Caenorhabditis elegans, was completed. The results (i) quantitatively indicated that pathways were conserved between evolutionarily disparate invertebrate species and (ii) emphasized the importance of the TOR kinase pathway in ageing.
The anti-aging effects of phloridzin on the yeast Saccharomyces cerevisiae were investigated by employing a replicative lifespan assay of the K6001 yeast strain. After administrating phloridzin at doses of 3, 10, and 30 µM, the lifespan of the yeast was significantly prolonged in comparison with the untreated group (p<0.01, p<0.001). To determine the mechanism of action, anti-oxidative experiments and ROS assay were performed.