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research team from The Scripps Research Institute (TSRI), Mayo Clinic, and other institutions have identified a new class of drugs, named ‘senolytics by the
researchers, which in animal models dramatically slows the ageing process by alleviating symptoms of frailty, improving cardiac function, and extending a healthy lifespan. The new research was published online ahead of print by the journal Aging Cell. ‘We view this study as a big, first step toward
developing treatments that can be given safely to patients to extend healthspan or to treat age-related diseases and disorders,’ said TSRI Professor Paul Robbins, PhD, who with Associate Professor Laura Niedernhofer, MD, PhD, led the research efforts for the paper at Scripps Florida. ‘When senolytic agents, like the combination we identified, are used clinically, the results could be transformative.’ ‘The prototypes of these senolytic agents
have more than proven their ability to alleviate multiple characteristics associated with ageing,’ said Mayo Clinic Professor James Kirkland, MD, PhD, senior author of the new study. ‘It may
eventually become feasible to delay, prevent, alleviate or even reverse multiple chronic diseases and disabilities as a group, instead of just one at a time.’
Finding the target Senescent cells—cells that have stopped dividing—accumulate with age and accelerate the ageing process. Since the ‘healthspan’ (time free of disease) in mice is enhanced by killing off these cells, the scientists reasoned that finding treatments that accomplish this in humans could have tremendous potential.
In a new paper, BBSRC-funded researchers at the University of Cambridge and Medical Research Council’s Cognition and Brain Sciences Unit demonstrated that previously reported changes in the ageing brain using functional magnetic resonance imaging (fMRI) may be due to vascular (or blood vessels) changes, rather than changes in neuronal activity itself. A problem of fMRI is that it
measures neural activity indirectly
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RESEARCHERS IDENTIFY NEW CLASS OF DRUGS THAT INCREASE HEALTHY LIFESPAN
found that, like cancer cells, senescent cells have increased expression of ‘pro-survival networks’ that help them resist apoptosis or programmed cell death. This finding provided key criteria to search for potential drug candidates. Using these criteria, the team homed in on
two available compounds—the cancer drug dasatinib (sold under the trade name Sprycel®) and quercetin, a natural compound sold as a supplement that acts as an antihistamine and anti-inflammatory. Further testing in cell culture showed these compounds do indeed selectively induce death of senescent cells. The two compounds had different strong points. Dasatinib eliminated senescent human fat cell progenitors, while quercetin was more effective against senescent human endothelial cells and mouse bone marrow stem cells. A combination of the two was most effective overall. The authors caution that more testing is needed before use in humans. They also note both drugs in the study have possible side effects, at least with long-term treatment.
NEW STUDY CHALLENGES THOERIES OF HOW THE BRIAN AGES
through changes in regional blood flow. Thus, without careful correction for age differences in vasculature reactivity, differences in fMRI signals can be erroneously regarded as neuronal differences. A candidate for correction makes
use of resting state fMRI measurements, which is easy to acquire in most fMRI experiments. The unique combination of an impressive data set across 335 healthy volunteers over the lifespan,
as part of the CamCAN project, allowed Dr. Kamen Tsvetanov and colleagues to probe the true nature of ageing effects on resting state fMRI signal amplitude. Their research showed that age
differences in signal amplitude during a task are of a vascular origin. They propose their method can be used as a correction factor to control for vascular differences in fMRI studies of ageing. The study also challenged previous
demonstrations of reduced brain activity in visual and auditory areas during simple sensorimotor tasks. Using conventional methods, the study replicated these findings. However, after correction, results show that it may be vascular health, not brain function, that accounts for most age-related differences in fMRI signal in sensory areas. Their results suggest that the age differences in brain activity may be overestimated in previous fMRI studies of ageing.
prime-journal.com | March 2015 ❚ 9
RESULTS FROM ANIMAL MODELS DEMONSTRATED THEY SLOWED THE AGEING PROCESS Using transcript analysis, the researchers
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