The 7KC-degrading bacterium I’ve been studying, Rhodococcus jostii RHA1, has two large gene clusters that are up-regulated by 7KC, but not cholesterol. In these two gene clusters lie a number of enzymes we believe are involved in 7KC degradation, including an enzyme that could reduce the 7-keto group to a hydroxyl. What makes this interesting to us is that while 7KC is highly cytotoxic, 7α-hydroxycholesterol (7αOH) is relatively harmless.
Haematopoietic stem cells (HSC) exhibit a range of functional declines during biological aging. There has been comparatively little exploration of the possibility of outside causes for age-related HSC dysfunctions, such as the role of age-related shifts in the systemic and local environment and the aging of the bone marrow niche. In a recent report, Dr. Amy Wagers' group have demonstrated the reality - and the reversibility - of both of these influences on age-related HSC dysfunction.
Last summer, California-based LifeStar Institute assembled a panel of leaders in the science of aging to ask them the question at the core of their research. "How far can the potential of new biomedical therapies to slow, arrest, or even reverse the damage of aging be brought to bear against the challenge of global graying?" The most important conclusion reached by the participants was that an aggressive program of investment to realize that potential is not only justified, but necessary on humanitarian, economic and social grounds.
A recent landmark report from researchers at Yale and Duke universities heralds a significant advance towards the tissue engineering of replacement lungs. Decellularised donor lungs repopulated with progenitor cells were matured in vitro and then implanted into living rats, where the tissue participated in gas exchange to an extent functionally approaching that of native lung tissue. This study represents a crucial proof-of-principle that the decellularisation/repopulation approach can be effective in another complex organ.
Neurites - projections from a neuron's cell body - become structurally abnormal in proximity to the extracellular aggregates that occur in both neurodegenerative disease and "normal" cognitive aging. These structural abnormalities have been suggested to play a role in cognitive pathology, by disrupting normal synaptic integration. Active immunotherapy against beta-amyloid (using the AN1792 antibody) has now been shown to reverse much of this structural deformity, even in cases where plaque clearance is incomplete.
New insights into the role of AID, a DNA demethylase, in the reprogramming process that produces induced pluripotent stem (iPS) cells are expected to allow greater efficiencies and permit the elimination of clinically problematic viral vectors and proto-oncogenes.
Serum amyloid P component (SAP) is a universal constituent of amyloid deposits, apparently regardless of the disease in question (and thus the other proteins present). Although methods have been developed to eliminate SAP from the body, this approach could have potentially serious side-effects. We announce a new SENS Research Foundation-funded project to tackle amyloid accumulation via the alternative, more direct approach of catalysing degradation of the pathogenic protein components.
The discovery of natural antibodies against beta-amyloid, the major component of the plaques that characterise Alzheimer's disease, is a promising suggestion as to the potential effectiveness of a relatively straightforward immunotherapy.
Affibodies are artificial, antibody-like proteins generated through protein engineering techniques. ZAβ3, an affibody that targets amyloid-beta (Abeta), has been shown to prevent plaque formation and neurotoxicity in animal models of Alzheimer's disease. Affibodies like ZAβ3 might have important practical advantages over antibody-based Abeta-clearing agents, making this a promising new approach.
Daniel Kimbel joined our SENS Foundation Research Center team this week as a lab technician. Daniel will be assisting Lorenzo Albanello with our LysoSENS projects already in progress. Coming to us with a BA in Biological Sciences from Rice University, Daniel has demonstrated his commitment to pursuing the SENS objectives, by volunteering both at the research center (while it was still in Tempe) and at Arizona State University's Biodesign Institute.
Widespread optimism about the life-extension potential of calorie restriction (CR) is tempered by doubt that any significant number of people will ever adopt it as a lifestyle. However, thus far the search for "CR mimetics" – drugs that convey the same benefits on a normal calorie intake - has been fruitless. Here we review some of the prominent examples.
Unlike mouse embryonic stem cells (ESCs), human ESCs are highly prone to death after enzymatic dissociation from a growing cell cluster; as a result, researchers are forced to rely on far more laborious methods for their expansion. New research at the Scripps Institute has revealed the molecular basis for this frustrating limitation, and also uncovered two small-molecule drugs able to greatly improve the cells' survival.