Animals

Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving "aging retardant" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid.

SIRT1 (sirtuin 1) is the human ortholog of the yeast Sir2 (silent information regulator 2) protein, which is implicated in lifespan extension in model organisms, such as yeast, worms and flies. It is an NAD+-dependent protein deacetylase with over two dozen known substrates that affect a wide variety of cellular processes, ranging from metabolism, cell cycle, growth and differentiation, inflammation, senescence, apoptosis, stress response and aging.

Studying the biological functions of the aryl hydrocarbon receptor (AhR) other than its function in xenobiotic drug metabolism may answer the questions as to why AhR orthologues have long been conserved phylogenically widely in the animal kingdom, and why homologues have diverged from nonvertebrate species such as nematodes and drosophila to all the vertebrate species.

Ethosuximide is a medication used to treat seizure disorders in humans, and we previously demonstrated that ethosuximide can delay age-related changes and extend the lifespan of the nematode Caenorhabditis elegans. The mechanism of action of ethosuximide in lifespan extension is unknown, and elucidating how ethosuximide functions is important for defining endogenous processes that influence lifespan and for exploring the potential of ethosuximide as a therapeutic for age-related diseases.

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.

Laboratory studies consistently demonstrate extended lifespan in animals on calorie restriction (CR), where total caloric intake is reduced by 10-40% but adequate nutrition is otherwise maintained. CR has been further shown to delay the onset and severity of chronic diseases associated with aging such as cancer, and to extend the functional health span of important faculties like cognition. Less understood are the underlying mechanisms through which CR might act to induce such alterations.

Spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality. SMA is caused by loss of functional survival motor neuron 1 (SMN1), resulting in death of spinal motor neurons. Current therapeutic research focuses on modulating the expression of a partially functioning copy gene, SMN2, which is retained in SMA patients. However, a treatment strategy that improves the SMA phenotype by slowing or reversing the skeletal muscle atrophy may also be beneficial. Myostatin, a member of the TGF-beta super-family, is a potent negative regulator of skeletal muscle mass.

Ageing in divergent animal phyla is influenced by several evolutionarily conserved signalling pathways, mitochondrial activity and various environmental factors such as nutrient availability and temperature. Although ageing is a multifactorial process with many mechanisms contributing to the decline, the intracellular accumulation of damaged proteins and mitochondria is a feature common to all aged cells.

Telomeres are the ends of chromosomes and are non-coding DNA "end-capped" with structures containing DNA-quadruplexes and proteins. Telomeres become shorter after each cell division, which is one of the mechanisms of gradual ageing. Telomerase is the reverse transcriptase responsible for the extension of telomere length. It is well known that activation of telomerase in the most types of organism's cells is not enough for telomere length stabilization. The reason may be in the telomere "caps", which cover telomere ends from telomerase action.

Enormous strides in understanding aging have come from the discovery that mutations in single genes can extend healthy life-span in laboratory model organisms such as the yeast Saccharomyces, the fruit fly Drosophila melanogaster, the nematode worm Caenorhabditis elegans and the mouse. IIS [insulin/IGF (insulin-like growth factor)-like signalling] stands out as an important, evolutionarily conserved pathway involved in the determination of lifespan.