A new study on biology of aging, published in PLoS Genetics, 2014; 10 (5): e1004354 DOI: 10.1371/journal.pgen.1004354
“G×G×E for Lifespan in Drosophila: Mitochondrial, Nuclear, and Dietary Interactions that Modify Longevity”,
showed that the factors influencing the lifespan (diet, mitochondrial DNA and nuclear DNA) are in complex interaction.
The new study examined dietary effects on aging in several panels of different nuclear and mitochondrial genetic pairings of Drosophila flies. For the study the scientists generated 18 lines of flies by mixing and matching different mitochondrial and nuclear genomes in individuals from two different species. Then they fed the flies with five different diets with varied balance between proteins and carbohydrates or different total of calories and constant proportion of nutrients.
In several cases, the team saw how interactions among the three factors they manipulated could produce results different than if they were too focused on just one factor. For example, in flies with the “w1118” nuclear genome and the “OreR” mitochondrial genome, lifespan was greatest with the high-sugar, low-yeast diet but significantly worse with the diet of evenly balanced yeast and sugar. For flies with the same nuclear genome but the “Zim” mitochondrial genome, the balanced diet was just as good, if not slightly better than the high-sugar, low-yeast meals.
The study’s results suggested that many observed effects of calorie or diet restriction or different genes on lifespan may depend on a more intricate context than has been understood so far.
Such studies could identify genetic interactions that themselves are modified by diet. Multifactorial interactions could help researchers to understand the inherent biological complexity of the aging process and explain why studies of single factors sometimes produced contradictory results.
Future works could focus on tracing the physiological and biochemical pathways suggested by these multidimensional interactions.
If someone thought till now that just by determining one longevity gene or factor (and then somehow introduce it in himself) or by following one specific diet, that he could extent his lifespan for indefinite time, he was most probably mistaken. Those of you, my friends, who didn’t know that aging is a complicated matter, well, you are certainly surprised, but c’est la vie… Don’t you despair now!
Here I see the future of complicated computer programmes charged with all our mitochondrial and nuclear genetic, microbiotic and other personal data, they could compare with the best combinations and suggest us the new diet and way of life. Finally, we could move to the personalised medicine!
A good example of how very complex human disease can be understood by use of mathematical models was published recently in PLoS Computational Biology, 2014; 10 (5): e1003634 DOI: 10.1371/journal.pcbi.1003634
By use of computational physiology model of the aging human aorta and using existing experimental health data, the researchers demonstrated that arterial stiffening seemed sufficient to explain age-related emergence of hypertension.
Hypertension is one of the most common age-related chronic disorders, and by predisposing individuals for heart failure, stroke, and kidney disease, it is a major source of morbidity and mortality. Despite intense research efforts over several decades, there is still no consensus on what are the primary causes of this disorder.
The model predictions in this study were compared with data on health history, taken from a study with 62 500 participants.
The researchers demonstrated that the stiffening of arterial wall caused the blood-pressure sensors located in the arterial wall (baroreceptors) to reduce signalling to the barosensitive sympathetic efferents and to misinform the highly complex machinery responsible for blood pressure regulation. By misinforming the autonomic nervous system about the actual blood pressure and thus preventing it from exerting a proper negative feedback response through regulation of the heart rate, vasculature and renal system, the compromised baroreceptor function then lead to an increasing baseline pulse pressure with increasing stiffening of the aortic wall.
This misinformation occurred because the baroreceptors were strain sensitive, not pressure sensitive, and with stiffening, the aortic wall strain ceased to be a good proxy for aortic blood pressure. Contrary to wide-held conceptions, the blood pressure regulation might thus become compromised without any other detrimental physiological change of the regulatory machinery.
These results therefore suggested that arterial stiffness represented a major therapeutic target by which an otherwise intact physiological machinery might be exploited for blood pressure regulation.
What a good news, friends, it is always better to have an intact physiological machinery! But now we have to find the way to clean somehow the plaque, causing the arterial stiffening with aging, may be we could try some diets, expecting the new targeted medications or much much better- we could try stop aging! It looks like the aging process is once more responsible!