Extending Healthy Lifespan: From Yeast to Humans

When the food intake of organisms such as yeast and rodents is reduced (dietary restriction), they live longer than organisms fed a normal diet. A similar effect is seen when the activity of nutrient-sensing pathways is reduced by mutations or chemical inhibitors. In rodents, both dietary restriction and decreased nutrient-sensing pathway activity can lower the incidence of age-related loss of function and disease, including tumors and neurodegeneration. Dietary restriction also increases life span and protects against diabetes, cancer, and cardiovascular disease in rhesus monkeys, and in humans it causes changes that protect against these age-related pathologies. Tumors and diabetes are also uncommon in humans with mutations in the growth hormone receptor, and natural genetic variants in nutrient-sensing pathways are associated with increased human life span. Dietary restriction and reduced activity of nutrient-sensing pathways may thus slow aging by similar mechanisms, which have been conserved during evolution. We discuss these findings and their potential application to prevention of age-related disease and promotion of healthy aging in humans, and the challenge of possible negative side effects

Chance and Causality in Ageing and Longevity

Longevity is not a matter of genes. This is the message that appeared last year in all the newspapers of the world, according to a study due to a joint venture between the statisticians of Ancestry and Calico Life Sciences that has dissected the genealogical trees of 400 million individuals, tracing back generations, and including dates of birth, death, places, and family ties. The genes would have little to do with longevity: in a percentage perhaps even less than 10% [1]. However, this extensive study has analysed the influence of genetics in terms of lifespan, but not in terms of longevity. Longevity may be defined in relative and absolute terms [2]. Longevity, indeed, may be considered a concept country/population specific, since different populations/countries show great variability of their life expectancy, represented by the age reached by 50% of a given population, owing to historical, anthropological, and socio-economic differences. In “absolute” terms, instead, longevity is defined according to the maximum lifespan attained and scientifically validated by human beings on the Earth (Chap. 4). The threshold of exceptional longevity is regarded the canonical age of 100........(abstract is not foresee, so we have uploaded the first part of introduction)

The quest to slow ageing through drug discovery

Although death is inevitable, individuals have long sought to alter the course of the ageing process. Indeed, ageing has proved to be modifiable; by intervening in biological systems, such as nutrient sensing, cellular senescence, the systemic environment and the gut microbiome, phenotypes of ageing can be slowed sufficiently to mitigate age-related functional decline. These interventions can also delay the onset of many disabling, chronic diseases, including cancer, cardiovascular disease and neurodegeneration, in animal models. Here, we examine the most promising interventions to slow ageing and group them into two tiers based on the robustness of the preclinical, and some clinical, results, in which the top tier includes rapamycin, senolytics, metformin, acarbose, spermidine, NAD+ enhancers and lithium. We then focus on the potential of the interventions and the feasibility of conducting clinical trials with these agents, with the overall aim of maintaining health for longer before the end of life