"Positive biology": the centenarian lesson

ABSTRACT: The extraordinary increase of the elderly in developed countries underscore the importance of studies on ageing and longevity and the need for the prompt spread of knowledge about ageing in order to satisfactorily decrease the medical, economic and social problems associated to advancing years, because of the increased number of individuals not autonomous and affected by invalidating pathologies.Centenarians are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases. Thus, they are the best example of extreme longevity, representing selected people in which the appearance of major age-related diseases, such as cancer, and cardiovascular diseases among others, has been consistently delayed or escaped. To discuss the relevance of genetics and life style in the attainment of longevity, five papers mostly focused on Italian centenarians have been assembled in this series. The aim is to realize, through a" positive biology" approach (rather than making diseases the central focus of research, "positive biology" seeks to understand the causes of positive phenotypes, trying to explain the biological mechanisms of health and well-being) how to prevent and/or reduce elderly frailty and disability.     

Endothelial nitric oxide synthase,vascular integrity and human exceptional longevity

Aging is the sum of the deleterious changes that occur as time goes by. It is the main risk factor for the development of cardiovascular disease, and aging of the vasculature is the event that most often impacts on the health of elderly people. The “free-radical theory of aging” was proposed to explain aging as a consequence of the accumulation of reactive oxygen species (ROS). However, recent findings contradict this theory, and it now seems that mechanisms mediating longevity act through induction of oxidative stress. In fact, calorie restriction ? a powerful way of delaying aging ? increases ROS accumulation due to stimulation of the basal metabolic rate; moreover, reports show that antioxidant therapy is detrimental to healthy aging. We also now know that genetic manipulation of the insulin-like-growth-factor-1/insulin signal (IIS) has a profound impact on the rate of aging and that the IIS is modulated by calorie restriction and physical exercise. The IIS regulates activation of nitric oxide synthase (eNOS), the activity of which is essential to improving lifespan through calorie restriction, as demonstrated by experiments on eNOS knockout mice. Indeed, eNOS has a key role in maintaining vascular integrity during aging by activating vasorelaxation and allowing migration and angiogenesis. In this review, we will overview current literature on these topics and we will try to convince the reader of the importance of vascular integrity and nitric oxide production in determining healthy aging.     

“Positive biology”: the centenarian lesson

The extraordinary increase of the elderly in developed countries underscore the importance of studies on ageing and longevity and the need for the prompt spread of knowledge about ageing in order to satisfactorily decrease the medical, economic and social problems associated to advancing years, because of the increased number of individuals not autonomous and affected by invalidating pathologies. Centenarians are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases. Thus, they are the best example of extreme longevity, representing selected people in which the appearance of major age-related diseases, such as cancer, and cardiovascular diseases among others, has been consistently delayed or escaped. To discuss the relevance of genetics and life style in the attainment of longevity, five papers mostly focused on Italian centenarians have been assembled in this series. The aim is to realize, through a?? positive biology?? approach (rather than making diseases the central focus of research, ??positive biology?? seeks to understand the causes of positive phenotypes, trying to explain the biological mechanisms of health and well-being) how to prevent and/or reduce elderly frailty and disability.     

An aprotinin binding site localized in the hormone binding domain of the estrogen receptor from calf uterus.

It has been proposed that the estrogen receptor bears proteolytic activity responsible for its own transformation. This activity was inhibited by aprotinin. Incubation of transformed ER with aprotinin modified the proteolytic digestion of the hormone binding subunit by proteinase K. The smallest hormone-binding fragment of the ER, obtained by tryptic digestion, was still able to bind to aprotinin. These results suggest that aprotinin interacts with ER and the hormone-binding domain of ER is endowed with a specific aprotinin-binding site.     

Hemorrhagic fever with renal syndrome associated with acute pancreatitis

Hemorrhagic fever with renal syndrome (HFRS) is a systemic infectious disease caused by Hantaviruses and characterized by fevers,bleeding tendencies,gastrointestinal symptoms and renal failure.It encom...