Thanks to the progress of medicine (Medicine (from the Latin medicus, « that heals ») is the science and the…) and modes of life (Life is the name given 🙂 healthier overall, more people are now living into their 80s than ever before. Yet the number (The notion of number in linguistics is treated in the article « Number…) over 100 years does not increase at the same rate. Is there a strict limit to the human lifespan, and if so, where is it written? « L’life expectancy (Life expectancy is a statistical data. It is supposed to allow to know the duration…) has increased dramatically over the past few decades, which is of course good news,” says David Vilchez, director of the Vilchez Lab and professor of medicine at theUniversity of Cologne (The University of Cologne (Universität zu Köln), founded in 1388, is one of…). « However, this demographic revolution also presents a challenge due to the increasing prevalence of age-related diseases. »
According to Vilchez, the aging (The notion of aging describes one or more diminishing functional changes…) is associated with a progressive loss of physiological integrity, which is a risk factor (In risk management, a risk factor is a source of risk that is classified into…) major for multiple metabolic, cardiovascular, oncological and neurodegenerative disorders. « The discovery of genetic manipulations that regulate aging has revolutionized the field of gerontology (Gerontology (< Gr. γέρων[gérōn)[gérōn) molecular, suggesting the realistic possibility of developing therapies for the prevention (Prevention is an attitude and/or the set of measures to be taken to avoid…) several diseases, » he explains. « Being able to define the mechanisms that can delay the aging process could be of enormous benefit to our ever-aging society, » adds Vilchez. However, the mechanisms underlying the aging process begins everything (The whole understood as the whole of what exists is often interpreted as the world or…) just to be elucidated at the molecular level.
Longevity factors
The discovery of a mutation genetic (Genetics (from the Greek genno γεννώ = to give birth) is…) unique that doubles the life expectancy of a worm (Worms are a very heterogeneous group of invertebrate animals…) nematode has radically changed the narrative of aging. « Previously, aging was seen as a cumulative process, where sickness (Disease is an alteration of the functions or health of a living organism, animal…) and general ‘wear and tear’ would eventually break the body and you would die, » he explains. « But this discovery really showed how point (graphics) aging is actually a regulated process. » Vilchez notes that the ability to manipulate genetic and environmental factors to extend longevity has also been found in other animals. « This could mean that it is also possible to extend longevity at themale (A man is an adult male individual of the species called Modern Man (Homo…) and that perhaps some of the pro-longevity factors discovered in invertebrates or mouse (The term mouse is an ambiguous vernacular name which can designate, for French speakers, before…) may also extend longevity in humans,” he says.
What Vilchez finds particularly interesting are embryonic stem cells, matter (Matter is the substance that makes up any body having a tangible reality. Its…) first from which each of the cells of our body is produced. « Because these cells are able to replicate indefinitely without showing any signs of aging, they are essentially immortal. » Thus, according to the theory (The word theory comes from the Greek word theorein, which means « to contemplate, to observe,…), if the mechanisms that contribute to the immortality of a stem cell are reproduced in other cells and tissues, we could potentially slow the natural aging process while preventing the development of many age-related diseases. “The result could be the key to further extending life expectancy and longevity,” concludes Vilchez.
The proteasome system
Mammalian cells typically contain over 10,000 proteins, tailored to cell function. Once proteins are synthesized or created, they are folded into a structure suitable for their function, but some fold and aggregate, degrading cellular function. Moreover, the stress (Stress (« constraint » in English), or general syndrome…), aging or disease-related mutations also cause degradation, leading to disease. A component of network (A computer network is a set of equipment linked together to exchange information…) of proteostasis called the proteasome removes these spent proteins. In StemProteostasis, the experiments focused on a nematode/worm called Caenorhabditis elegans. With her biology (Biology, commonly called « bio », is the science of life….) sharing many mammalian characteristics and its lifespan of 19 days (The day or the day is the interval which separates the sunrise from the sunset; it is the…)it is a favorite of the research (Scientific research designates in the first place all the actions undertaken with a view to…) and is therefore accompanied by well-established genetic manipulation protocols and age-related disease models.
The team had previously found that hESCs increased theactivity (The term activity can refer to a profession.) of the proteasome through high levels of a molecular activator called RPN-6, which also helps stem cells differentiate into specific cells. L’experimentation (Experimentation is a scientific method of testing through experiments…) yielded the key discovery that by mimicking this process, increasing levels of RPN-6 in differentiated C. elegans cells, the longevity of theanimal (An animal (from the Latin animus, spirit, or vital principle) is, according to the classical classification, a…) was prolonged and the accumulation of disease-related proteins was delayed. « This clearly tells us that the proteasome regulates (Regules are alloys of tin or lead and antimony.) not only hESC/iPSC but also aging and the onset of age-related diseases,” says Vilchez.enzyme (An enzyme is a molecule (protein or RNA in the case of ribozymes) allowing…) UBR5 E3, the chaperonin subunit CCT8 and the protein (A protein is a biological macromolecule composed of one or more…) CSDE1 RNA-binding molecules – which suppress aggregation of disease-related proteins in human stem cells and influence differentiation.
The team found that modulating UBR5 or CCT8 can suppress the accumulation of disease-related proteins in neurons, while extending the organism’s longevity. Unexpectedly, they also discovered that RNA-binding proteins in germline stem cells play a role in the regulation (The term regulation refers in its concrete sense to a technical discipline, which is…) longevity and protein aggregation in neurons, offering hope for a better understanding of HD and ALD. “One of the biggest surprises was the challenge to the established paradigm that long life leads to reduced fertility (For common sense, fertility designates at the end of the 20th century the…). We discovered that germline stem cells can harvest data (In information technology (IT), data is an elementary description, often…) environmental influences and communicate them to somatic tissues, such as neurons, to increase fertility while preserving longevity, » adds Vilchez.
Meet the challenges ahead
By 2050, the world population (World population refers to the number of human beings living on Earth at one…) over 80 is expected to triple. Although this is a positive result for the health (Health is a state of complete physical, mental and social well-being, and is not…), this trend will lead to an increase in the prevalence of age-related diseases, with the associated financial and social burdens. « The molecular mechanisms underlying aging are only beginning to be unraveled and we are proud to open many new doors for research, » says Vilchez. The datasets of the project (A project is an irreversible commitment of uncertain result, not reproducible to…)proteomics methodology and specially created bioinformatics tools are now publicly available.
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