Welcome to this lesson on aging. Ever since the turn of the last century, life expectancy has been steadily increasing. As you can see from the graph, in 1900, it was just below the 50 years of age mark. And ever since, it increased steadily upwards until today reaching the 80 years of age mark for both, males and females. And predictions for the future foresee an even further steady increase. This is of course good news except for the fact that together with increasing age, the incidences of cardiovascular disease as well as stroke increase dramatically. Indeed, as you can see from the graph, from the age of 65 years onwards, an increasingly large number of males and females are affected by either one form of the disease or another. And from the age of 75 onwards, around two-thirds of the population is affected by either heart disease or stroke. First, does increasing life expectancy together with an increasingly large number of elderly people in our society mean that we're soon going to be faced with an aging pandemic? For this very reason, it is important to study the molecular mechanisms, by which aging induces age-dependent cardiovascular disease as well as cerebrovascular disease. This is going to be crucial not only for identifying the noble potential therapeutic target for the improvement of the quality of life of elderly people, but also for releasing pressure from our healthcare providers, which will soon be faced with a larger percentage of elderly patients. Studying aging in humans is a difficult task. And this is because aging doesn't occur alone, but rather, in concomitance to other risk factors which develop spontaneously, such as atherosclerosis. Thus, it becomes difficult to attribute the changes observed with aging to either aging or to the concomitant risk factor. From this point of view, animal models of aging offer an ideal system to study aging. This is because they age, and they develop age-dependent organ dysfunctions. However, they do not develop spontaneously occurring risk factors. Thus, making any observed change directly attributable to aging itself. The most widely accepted theory to explain aging from a molecular point of view, is the free radicals theory of aging. This theory was first proposed by a German physician called D Harman in the 1950s. And it states that over the course of a lifetime, the production of free radicals increases. And beyond a certain age, these free radicals accumulate to above a threshold, which becomes toxic, eventually leading to DNA damage and cellular organelles damage, which in turn, leads to cellular dysfunction, cell death, and organ dysfunction. From a vascular/endothelial point of view, aging is a very complicated phenomenon: Indeed, the endothelium, which is the innermost layer of a vessel, goes from its physiological role, which is an anti-atherosclerotic, and an anti-thrombotic role, which is observed at a young age. Gradually, it shifts to the opposite. So, it becomes pro-atherosclerotic and pro-thrombotic with increasing age. Thus, favoring the development of cardiovascular disease. In our laboratories, we study aging, and our working hypothesis is depicted in the cartoon in this slide. We believe that aging genes not only mediate aging itself but also mediate the onset of age-dependent cerebrovascular as well as cardiovascular disease. And this often occurs via common mechanisms, which involve an increased production of free radicals. First, elucidating the mechanisms by which aging genes induce aging may also shed some light onto how aging induces age-dependent cerebrovascular and cardiovascular disease. In keeping with our working hypothesis, we were able to study several aging genes, and in this slide, we represent some of our findings with a specific aging gene called p66Shc. With this gene, we were not only able to show that it mediates aging, but we were also able to show that it mediates the onset of hypertension-dependent vascular damage, age-related vascular dysfunction, stroke, as well as diabetes-induced vascular dysfunction. All of which are conditions that are increasingly encountered with ascending age in different patients. First, in conclusion, we can say that aging is a major and independent risk factor for the development of cardiovascular disease. Studying the mechanisms by which it causes cardiovascular disease will be crucial not only to improve the quality of life in the elderly but also to prevent the collapse of our healthcare systems worldwide. Finally, blunting the increasing production of free radicals, that is observed with aging, may represent an interesting therapeutic option for the treatment of this condition. Thank you for your attention.
