Erasing the signs of aging in cells is now a reality

Inserm’s AVENIR “Genomic plasticity and aging” team, directed by Jean-Marc Lemaitre, Inserm researcher at the Functional Genomics Institute (Inserm/CNRS/Université de Montpellier 1 and 2), has recently succeeded in rejuvenating cells from elderly donors (aged over 100). These old cells were reprogrammed in vitro to induced pluripotent stem cells (iPSC) and to rejuvenated and human embryonic stem cells (hESC): cells of all types can again be differentiated after this genuine “rejuvenation” therapy. The results represent significant progress for research into iPSC cells and a further step forwards for regenerative medicine.The results are published in the Genes & Development Journal dated 1 November 2011.

Human embryonic stem cells (hESC) are undifferentiated multiple-function cells. They can divide and form all types of differentiated adult cells in the body (neurones, cardiac cells, skin cells, liver cells, etc., see Figure 1).
Since 2007, a handful of research teams across the world have been capable of reprogramming human adult cells into induced pluripotent cells (iPSC), which have similar characteristics and potential to human embryonic stem cells (hESC). This kind of reprogramming (see Figure 1, opposite, in red) makes it possible to reform all human cell types without the ethical restrictions related to using embryonic stem cells.

Until now, research results demonstrated that senescence (the final stage of cellular aging) was an obstacle blocking the use of this technique for therapeutic applications in elderly patients. Today, Inserm researcher Jean-Marc Lemaitre and his team have overcome this obstacle. The researchers have successfully rejuvenated cells from elderly donors, some over 100 years old, thus demonstrating the reversibility of the cellular aging process.

Figure 1 – © INSERM

To achieve this, they used an adapted strategy that consisted of reprogramming cells using a specific “cocktail” of six genetic factors, while erasing signs of aging. The researchers proved that the iPSC cells thus obtained then had the capacity to reform all types of human cells. They have the physiological characteristics of “young” cells, both from the perspective of their proliferative capacity and their cellular metabolisms.

A cocktail of six genetic factors…

Researchers first multiplied skin cells (fibroblasts) from a 74 year-old donor to obtain the senescence characterized by the end of cellular proliferation. They then completed the in vitro reprogramming of the cells. In this study, Jean-Marc Lemaitre and his team firstly confirmed that this was not possible using the batch of four genetic factors (OCT4, SOX2, C MYC and KLF4) traditionally used. They then added two additional factors (NANOG and LIN28) that made it possible to overcome this barrier (see Figure 2).

Using this new “cocktail” of six factors, the senescent cells, programmed into functional iPSC cells, re-acquired the characteristics of embryonic pluripotent stem cells.

In particular, they recovered their capacity for self-renewal and their former differentiation potential, and do not preserve any traces of previous aging.
To check the “rejuvenated” characteristics of these cells, the researchers tested the reverse process. The rejuvenated iPSC cells were again differentiated to adult cells (see Figure 1) and compared to the original old cells, as well as to those obtained using human embryonic pluripotetent stem cells (hESC).

“Signs of aging were erased and the iPSCs obtained can produce functional cells, of any type, with an increased proliferation capacity and longevity,” explains Jean-Marc Lemaitre who directs the Inserm AVENIR team.

… Tested on cells taken from donors over the age of 100

The results obtained led the research team to test the cocktail on even older cells taken from donors of 92, 94 and 96, and even up to 101 years old. “Our strategy worked on cells taken from donors in their 100s. The age of cells is definitely not a reprogramming barrier.” He concluded. “This research paves the way for the therapeutic use of iPS, insofar as an ideal source of adult cells is provided, which are tolerated by the immune system and can repair organs or tissues in elderly patients.” adds the researcher.
Inserm Transfert filed a patent request for this research.

This article is an extract from the INSERM’s website. All rights reserved.
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How the popularization of the web is tranforming our relationships

This article is an extract of the National Institute Computer Research INRIA website. All rights reserved. Marie Varandat, Oct 7, 2011.

Internet of the New opportunities, new challenges, new risks and new fears are emerging. The Internet of the future, gradually taking shape right now in the research field, has generated numerous debates concerning among other things the protection of privacy.

A debate between Anne-Marie Kermarrec (Senior Research Scientist) and Dominique Cardon (Sociologist).

What are the great milestones of the Internet of the future? What is the major challenge?

Anne-Marie Kermarrec: : Internet usage has changed considerably over the years. Originally reserved for military personnel, it was subsequently used by academic staff. Later, the general public also gained access to it, initially as readers and consumers and today as content producers in their own right, leaving traces and information each time they go online.

Dominique Cardon: This “popularization” of the web is also changing our social behaviour. Back in the pioneering days, the Internet was reserved for a select group of people, most of whom were highly educated. However, with the emergence of social networks in the mid-2000s, all web users now have the possibility to become both readers and participants, thanks to the convergence of communication and publication media technologies. As the pioneers saw it, the web was a completely separate world. Today, it cannot be denied that it has become part of our everyday lives. Our real and virtual lives are increasingly converging.

Anne-Marie Kermarrec: These changes were neither planned nor anticipated. They have left us with some real problems, particularly in terms of data confidentiality and privacy protection. Although the Internet was originally designed as a “web” to limit the risk of the network being destroyed in the event of an attack, the fact nevertheless remains that the data is centralised in the hands of a number of major companies such as Google and Facebook. As this change had not been planned for from a legislative viewpoint, the confidentiality guarantees provided by these companies are relatively weak or even non-existent. Faced with the danger of a “Big Brother” situation emerging, it is now vital to conceive the Internet from something other than a technical angle and to initiate major changes by encouraging the decentralisation of data. The goal must be to bring about the disappearance of “central authorities” possessing complete information about individuals.

Dominique Cardon: The risk is not limited to companies taking control. The centralisation of information can also take place at a state level. We can easily imagine the possibilities for political misbehaviour which arise from such a situation.

Anne-Marie Kermarrec: This problem is central to the work which we are currently undertaking at Inria. Faced with such a danger, we need technology capable of decentralising web functions. Typically, rather than using a search engine on the Internet, the user has a function which, at a given moment, combines several services in order to provide the best possible response.

Moving from an Internet run by companies to an Internet focused on its users.

In other words we will be moving from an Internet run by companies to an Internet focused on its users, in which the services will be combined according to needs, within a precise framework and for a given timeframe. Technically, the task before us is a complex one but is by no means insurmountable. This move to a user-centric Internet must also open up new perspectives regarding the filtering of information – another key challenge for the Internet of the future. Between emails, blogs, websites and chat rooms, today’s web users are drowning under a sea of information. I don’t have any solutions to propose here, but it is clear that we need to find a way of optimising the circulation of information and filtering it to ensure greater relevancy.

Dominique Cardon: Where individuals are concerned, today’s Internet has brought with it some major social repercussions. The dream of democratisation on the part of the pioneers (everyone communicating with everyone) has not become reality. The reason for this is fairly simple. Although the Internet facilitates contact in the virtual world, the principles governing social relationships have remained the same. In other words, in both the virtual world and the real world, people only communicate when they have shared interests. The result is that the Internet has not broken down social and cultural barriers. The groups remain the same. The key players and extroverts of the virtual world are the same as those in the real world whereas the shy and thoughtful types, who nevertheless exist as a real-world group, are disappearing in the virtual world. Other changes likely to have major social consequences are currently underway. Our relationship to paper-based written material is declining while our relationship to writing in general is being transformed. Web users are faced with overabundant information while the numerous economic models generated by the Internet have trouble existing alongside the older models. And these changes are accompanied by the new risk of surveillance and tracking.

Although centralisation brings with it no positive benefits, it must be remembered that interpersonal, decentralised surveillance will also have an effect upon our societies.

I share Anne-Marie Kermarrec’s opinion of the dangers of data centralisation, but I am even more alarmed by the phenomenon of interpersonal surveillance, which has been particularly heightened through the use of social networks. In a more or less consensual manner, web users are publishing enormous amounts of information and are monitoring one another. The boundary between private discussions and public content has not yet been truly established. Collecting data about a given individual is therefore relatively simple and such information can then be used out of context. As an example, a private conversation may be viewed by a recruiter and used to the advantage or detriment of a possible candidate. The relationship between parents and their children may also be affected. To sum up, although centralisation brings nothing positive for us, interpersonal and decentralised surveillance also looks set to turn our society upside down.

Five new genetic susceptibility factors identified for Alzheimer’s disease

A consortium of 108 European laboratories coordinated by a French team (“Public Health and molecular epidemiology of diseases related to aging” UMR 744 Inserm-Lille-Institut Pasteur de Lille) led by Professor Philippe Amouyel (director of the 2010 FAID seminar) and a British team (Centre for Genetic and Genomic Neuropsychiatry, University of Cardiff) have recently identified five new genetic predisposition factors involved in the development of the disease.

The research was conducted by Inserm in close collaboration with the CEA (French national genotyping centre, CEA-IG-CNG), the Fondation Jean Dausset-CEPH and a European consortium of 25 teams.

The discoveries were made thanks to support from the Fondation Plan Alzheimer, which coordinated the research section of the plan, launched in February 2008, to fight Alzheimer’s and other related diseases.

See the full article here.