A Brace of Open Access Papers on the Genetics of Longevity

The latest issue of the open access journal Immunity & Aging includes a number of interesting papers covering the overlap between genetic contributions to natural variations in longevity and the aging of the immune system - which contributes to a range of age-related dysfunction and systems failure. They are very much in the mainstream model of narrow, unambitious, cautious vision: aiming for and expecting only modest, gradual improvements in health and longevity. Even in this time of radical change in biotechnology, the old habits of incrementalism and understatement regarding the bounds of the possible for human longevity are only slowly fading. The future must be one of ambitious, grand visions in medical science and funding for research if we are to benefit fully from the true potential of biotechnology. In any case, these papers remain interesting for what they are, and are available as provisional PDFs at this time - the download links are on the abstract pages below.

"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. ... 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.

Epidemiological, genetic and epigenetic aspects of the research on healthy ageing and longevity:

In this article we aimed to overview the research on the biological basis of human healthy ageing and longevity, discussing the role of epidemiological, genetic and epigenetic factors in the variation of quality of ageing and lifespan, including the most promising candidate genes investigated so far. Moreover, we reported the methodologies applied for their identification, discussing advantages and disadvantages of the different approaches and possible solutions that can be taken to overcome them.

Genetics of longevity. Data from the studies on Sicilian centenarians:

Scientists have focused their attention on centenarians as optimal model to address the biological mechanisms of "successful and unsuccessful ageing". They 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, such as cardiovascular diseases and cancer. Thus, particular attention has been centered on their genetic background and immune system. In this review, we report our data gathered for over 10 years in Sicilian centenarians. Based on results obtained, we suggest longevity as the result of an optimal performance of immune system and an over-expression of anti-inflammatory sequence variants of immune/inflammatory genes.

Extending healthy ageing: nutrient sensitive pathway and centenarian population:

To increase our understanding of how ageing works, it may be advantageous to analyze the phenotype of centenarians, perhaps one of the best examples of successful ageing. Healthy ageing involves the interaction between genes, the environment, and lifestyle factors, particularly diet. Besides evaluating specific gene-environment interactions in relation to exceptional longevity, it is important to focus attention on modifiable lifestyle factors such as diet and nutrition to achieve extension of health span. Furthermore, a better understanding of human longevity may assist in the design of strategies to extend the duration of optimal human health.

The application of genetics approaches to the study of exceptional longevity in humans: potential and limitations:

The average life-span of the population of industrialized countries has improved enormously over the last decades. Despite evidence pointing to the role of food intake in modulating life-span, exceptional longevity is still considered primarily an inheritable trait, as pointed out by the description of families with centenarian clusters and by the elevated relative probability of siblings of centenarians to become centenarians themselves. However, rather than being two separate concepts, the genetic origin of exceptional longevity and the more recently observed environment-driven increase in the average age of the population could possibly be explained by the same genetic variants and environmentally modulated mechanisms (caloric restriction, specific nutrients). In support of this hypothesis, polymorphisms selected for in the centenarian population as a consequence of demographic pressure have been found to modulate cellular signals controlled also by caloric restriction.
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