The fifth biannual Strategies for Engineered Negligible Senescence biomedical conference is just days away. Getting ready for the trip has cast my mind back not only to previous meetings of this exciting interdisciplinary series, and also to the recent 40th meeting of the American Aging Association (AGE). AGE was the first, and remains the premier, professional scientific organization focused specifically on biomedical research in aging.
A comprehensive suite of rejuvenation biotechnologies must include the removal of extracellular aggregates from aging cells and tissues, particularly the brain. Recent work indicates that up-regulation of the activity of the native lysosomal pathway for clearance of beta-amyloid (Abeta) by the small molecule PADK can reverse existing Alzheimer-like pathology in mouse models, although caution is required in interpreting these results in the context of human disease.
I recently travelled to Zaragosa, Spain, to attend the eighth European Meeting on Mitochondrial Pathology (Euromit 8). The conference was extremely relevant to the MitoSENS project, and I was very lucky to have the opportunity to attend. For me, the most striking aspect of this scientific conference was the cross-sectional interaction between clinicians and basic scientists.
Neurofibrillary tangles - accumulations of abnormal tau protein - are thought to play a central role in Alzheimer's disease and other neurodegenerative conditions. Here we review a recent report in which immunotherapy was used to clear tau aggregates from a highly accurate mouse tauopathy model, resulting in functional recovery on multiple cognitive tests.
Efficient, safe methods of gene therapy will be essential enabling technologies for the repair or obviation of several of the cellular and molecular lesions driving age-related disease and dysfunction. A recent paper from the Scripps Institute demonstrates a major step in this direction with the successful use of helper-dependent adenoviral vectors to rescue cells defective in lamin A, without detectable mutational side-effects.
At the third SENS conference, Dr. Samit Adhya of the Indian Institute of Chemical Biology presented a proof-of-principle for the use of an RNA import complex adapted from the parasite Leishmania to import arbitrary antisense RNA strands into mammalian mitochondria, reducing levels of a target protein by RNA interference. In a new study, Adhya's group reports the successful use of the same technique to deliver mRNA sequences corresponding to proteins of the electron transfer chain, rescuing mitochondrial function in cells with mutations or deletions in those genes.
Dr. Doris Taylor, the researcher whose team successfully engineered a live, beating rat heart via the technique of decellularisation and reseeding, has announced progress towards repeating the process with human tissue. Press reports based on Dr. Taylor's presentation at the American College of Cardiology's 60th Annual Scientific Session indicate that the hearts are growing well and are expected to begin beating within the next few weeks.
Much of the distraction in the literature of biogerontology, and an even higher ratio of studies cited and promoted in the popular media and the dietary supplement industry, derives from methodologically-poor lifespan studies in mice (or occasionally rats). In these studies, an increase in mean or maximal lifespan is reported, relative to short-lived controls, and claimed to be informative about the universal, degenerative aging process and the prospects for extending healthy life in humans living in the developed world.
I'm delighted to be able to share with you our research report, prepared for the first 10 months of 2010, by Tanya Jones (our Director of Research Operations), working with our researchers and my CSO Team.
The free radical theory of aging suggests that reactive oxygen species (ROS) and similar chemicals are responsible for a large part, or perhaps all, of the molecular and cellular damage that accumulates in aging bodies. However, more detailed analysis has revealed that some free radicals have essential signalling functions within the cell. These functions are likely to explain some of the failure of antioxidant therapy to extend lifespans in model organisms.
Two recent publications clearly refute the principle arguments in favour of a distinction between "normal" cognitive aging, and pathological conditions such as Alzheimer's disease. Instead, it is increasingly apparent that the "normal" cognitive decline observed in all elderly and some middle-aged individuals is simply an earlier stage of the frank neuropathology observed in neurodegenerative disease. We emphasise that treating such conditions at this earlier, pre-clinical stage is likely to be more effective, as well as being more humane.
The degenerative aging of the immune system is responsible for an enormous burden of disease and disability, from the pain of recurrent Herpes zoster and postherpetic neuralgia, to elevated rates of chronic urinary tract infections, to complications in wounds, pressure sores, ulcers, and surgical incisions. Most prominently, it underlies the meteoric rise in mortality from respiratory infections with age: influenza, pneumonia, and septicemia rise from being negligible causes of death in healthy middle-aged adults in the USA, to emerge amongst the top 10 causes of death in adults over the age of 55, with mortality rates climbing with each successive year of aging.