Telomere lengthening via gene therapy achieved for the first time

U.S. biotech company BioViva has announced the first successful use of gene therapy to extend telomeres, believed to be vitally important in the fight against human aging.
In September 2015, then 44 year-old CEO of BioViva, Elizabeth Parrish, received two of her own company's experimental gene therapies: one to protect against loss of muscle mass with age; another to battle stem cell depletion responsible for diverse age-related diseases and infirmities.

The treatment was originally intended to demonstrate the safety of the latest generation of the therapies. But if early data is accurate, it is already the world's first successful example of telomere lengthening via gene therapy in a human individual. Gene therapy has been used to lengthen telomeres before in mice and in cultured cells – but never in a human patient, until now.

Telomeres are short segments of DNA which cap the ends of every chromosome. Like the plastic tips on shoelaces that stop them from fraying, they act as 'buffers' against wear and tear. With every cell division they become shorter, eventually getting too short to protect the chromosome, causing the cell to malfunction and the body to age.

In September 2015, telomere data from Parrish's white blood cells (immediately before therapies were administered), revealed that her telomeres were unusually short for her age, leaving her vulnerable to age-related diseases earlier in life.

In March 2016, following BioViva's treatment, the same tests taken again revealed that her telomeres had lengthened by the equivalent of 20 years, from 6.71kb to 7.33kb – implying that Parrish's white blood cells (leukocytes) had become biologically younger. These findings were independently verified by the non-profit, Brussels-based HEALES (HEalthy Life Extension Company), and the Biogerontology Research Foundation, a UK-based charity committed to aging research.

"Current therapeutics offer only marginal benefits for people suffering from diseases of aging," Parrish commented. "Additionally, lifestyle modification has limited impact for treating these diseases. Advances in biotechnology are the best solution, and if these results are anywhere near accurate, then we've made history."

BioViva will continue to monitor Parrish's blood for months and years to come. Meanwhile, the company will be testing new gene therapies and combination gene therapies to restore age-related damage. It remains to be seen whether the success in leukocytes can be expanded to other tissues and organs, and repeated in future patients with larger sample sizes. For now, all the answers lie in the cells of Elizabeth Parrish, "patient zero" of restorative gene therapy.

Since her first gene therapy injections, BioViva has received global interest from both the scientific and investment communities. Earlier this month, BioViva became a portfolio company of Deep Knowledge Life Sciences (DKLS), a London-based investment fund which aims to accelerate the development of biotechnologies for healthy longevity.

Dmitry Kaminskiy, founding partner of DKLS, said: "Many innovative companies have come to us looking for funding and support. BioViva is one among several other breakthrough companies that are going to leapfrog the current generation of biotech and will be included in our portfolio. This is the start of a big trend, and it ought to give investors food for thought. 2017 will be the year in which we will see an investment boom in the longevity industry."Source:
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Why Men Find Switching Tasks More Difficult Than Do Women

It has long been known to science that women find it easier than men to multitask and switch between tasks. But identifying exactly which areas of male and female brains respond differently and why has so far been unclear. According to researchers from the HSE Neurolinguistics Laboratory, men need to mobilise additional areas of their brain and use more energy than women when multitasking.

Why Men Find Switching Tasks More Difficult

Needing to switch attention between tasks causes stronger activation in certain brain regions in men compared to women.

Although women find it easier than men to switch between tasks; how exactly their brains function differently in such situations has so far been unknown. Recent research reveals that male brains appear to consume more energy when they need to shift attention. In addition to this, in men there is greater activity in the dorsolateral prefrontal areas of the brain compared to women, as well as activation in some other areas which is not usually observed in women.

Such differences are typical of younger men and women aged 20 to 45, according to findings from experiments conducted by researchers Svetlana Kuptsova and Maria Ivanova of the HSE Neurolinguistic Laboratory, radiologists Alexey Petrushevsky and Oksana Fedina of the Centre for Speech Pathology and Neurorehabilitation, and Ludmila Zhavoronkova, Doctor of Biology and Senior Research Fellow of the RAS Institute of Higher Nervous Activity and Neurophysiology. The study's findings have been published in Human Physiology, an international peer-reviewed journal.

Higher Activity, Slower Speed

Regardless of gender and age, task switching always involves activation in certain areas of the brain, more specifically, bilateral activation of the dorsolateral prefrontal areas, inferior parietal lobes and inferior occipital gyrus.

However, experiments conducted by Kuptsova et al. demonstrate that in women, task switching appears to require less brain power compared to men, who showed greater activation in the dorsolateral prefrontal areas as well as the involvement of supplementary motor areas and insula, which was not observed in women.

"We know that stronger activation and involvement of supplementary areas of the brain are normally observed in subjects faced with complex tasks. Our findings suggest that women might find it easier than men to switch attention and their brains do not need to mobilise extra resources in doing so, as opposed to male brains," explained Kuptsova.

The experiments involved 140 healthy volunteers, including 69 men and 71 women aged between 20 and 65. The subjects were asked to perform a variety of tasks. In one of the experiments using functional MRI, they were asked to perform a test that required switching attention between sorting objects according to shape (round or square) and number (one or two), in a pseudo-random order. In addition to this, neuropsychological tests were conducted, including the D-KEFS Trail Making Test to measure the subjects' ability to switch attention and the Wechsler Memory Scale test to measure their audial and visual memory.

The use of functional MRI allowed the researchers not only to observe the subjects' behaviour, but also to see what was going on in the brain as subjects switched between tasks and detect differences in brain activation between men and women.

Age versus Gender

The researchers found that the gender differences in the extent of brain activation when switching between tasks only occurred in subjects younger that 45-50, while those aged 50 and older showed no gender differences either in brain activation or speed of task switching.

According to the researchers, older men and women - starting at the age of 45 in women and 55 in men - experienced both increased activation of key areas involved and mobilisation of additional brain resources.

Brain Mystery

The study has once again confirmed that young women tend to cope with attention switching better than young men. While the reaction time is demonstrably different, according to Kuptsova, it is barely noticeable in everyday life, except perhaps that, "it might make a difference in really stressful circumstances or in critical situations which require frequent switching of attention."

However, science cannot currently explain the exact reasons for this difference. Any assumptions as to why nature might need it are nothing but speculation, Kuptsova argues.

For example, there is a popular hypothesis by American psychologist Jerre Levy as to why men tend to have better spatial skills while women are often better at more verbal tasks. According to Levy, these differences are caused by both evolutionary and social factors. In ancient times, men spent their time hunting, which required good spatial abilities, while women were caring for children and thus needed good communication skills. In the course of evolution, these survival skills have been passed down to future generations.

"We could continue with the same logic and assume that homemaking and caring for children historically required women to be good at multitasking, but there is no hard evidence to support this theory," Kuptsova concludes.

The study was hosted by the Centre for Speech Pathology and Neurorehabilitation.

Contacts and sources:
National Research University - Higher School of Economics (HSE)

Citation: Sex- and age-related characteristics of brain functioning during task switching (fMRI study) Authors Authors and affiliations S. V. KuptsovaEmail authorM. V. Ivanova, A. G. Petrushevskiy, O. N. FedinaL. A. Zhavoronkova. Human Physiology July 2016, Volume 42, Issue 4, pp 361–370 2016 DOI: 10.1134/S0362119716040101 Source:
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