Aging and lifespan have long been considered “probabilistic events”. Therefore, it has taken longer for researchers to apply genetic and molecular biological approaches to aging than to other life science fields, such as developmental biology. However, several aging control signals have recently been reported, not only in lower organisms but also in higher organisms. These signals, which include insulin/insulin-like growth factor-1 (IGF-1), sirtuin 1 (SIRT1) and, mammalian target of rapamycin (mTOR) signaling pathways, appear to be evolutionally conserved among these organisms. Moreover, several compounds have been reported to extend the lifespan of these experimental animals. Most of these compounds are calorie restriction mimetics, i.e. they mimic the anti-aging effects of calorie restriction without actual dietary restriction. In the United States, there is a large-scale human clinical trial in progress for one of those compounds, the results of which will be apparent over several years. In this report, we discuss the aforementioned aging control signals and anti-aging compounds that extend the lifespan of experimental animals. Further, we discuss how phytochemicals have the potential to act as anti-aging compounds by modulating the aging control signals.

Long term caloric restriction (CR) retards age-related pathophysiological changes and extends median and maximum lifespans in various animals. Therefore, CR is accepted as a robust, reproducible and simple experimental manipulation that is widely used in aging research. Several molecular mechanisms including suppression of growth hormone (GH) /insulin-like growth factor 1 (IGF1) signal, reduced mechanistic target of rapamycin complex 1 activity, activation of sirtuin, improvement of mitochondria/redox regulation, remodeling of white adipose tissue might be involved in the beneficial actions of CR, but the exact mechanism is still debated. In this review, we discuss the molecular mechanisms of the beneficial actions of CR based on the evidences using genetically modified rodents obtained by the recent advance of molecular and genetic technologies.

Glycation is a non-enzymatic chemical reaction between amino acid or protein and reducing sugar and it occurs to various proteins in living organisms. The glycated protein leads to the formation of advanced glycation end products (AGEs) through the formation of intermediates dominated by carbonyl compounds. Glycative stress is a concept of comprehensively viewing the stress to living organisms caused by the loads of reducing sugar and aldehyde and its subsequent reactions. Glycative stress is considered a risk factor for aging in anti-aging medicine. Various substances produced in the course of glycation reaction can be used as markers for the evaluation of glycative stress. The glycative stress markers in the stage before the production and accumulation of AGEs include blood glucose, glycated protein and intermediates for AGEs. When measuring anti-glycative effects, test samples are added into the phosphate buffer solution including proteins and reducing sugars so that glycation occurs. Then, the amount of AGEs, as well as the amount of intermediate glycative reaction products are measured. A lot of food and cosmetic materials with the effect of the antiglycation are found. We are using these materials and can prevent the aging or the disease by a glycative stress.