Aging laboratory rodents are the foundation of our ability to study the degenerative aging process, and develop the rejuvenation biotechnologies that will arrest and reverse it. They're also expensive, logistically intensive, and in short supply. A new UK initiative has been establish to greatly expand what we can learn from the aging animals in our collective care, and to get a fuller picture of aging and its deceleration and reversal than has hitherto been possible.
Recent studies show the potential - and the limits - of inducing telomerase expression in aging mice. We place these results in context and explore their implications for new treatments targeting age-related degeneration in humans, particularly examining how telomerase activity relates to the development of cancer.
SENS Foundation-funded research shows that expression of a modified microbial enzyme protects human cells against 7-ketocholesterol toxicity, advancing research toward remediation of the foam cell and rejuvenation of the atherosclerotic artery.
UCLA Researchers have exploited a recently-discovered mammalian system for the mitochondrial import of nuclear-encoded RNA to import, express, and demonstrate functional protein translation from engineered mRNA and tRNA constructs. They used this system, with modifications for mitochondrial targeting and orthotopic translation, to rescue respiration in human mitochondriopathy cells. While further characterization and extension is clearly needed, this approach appears offer great promise for the correction of age-related mitochondrial DNA mutations.
The promising results of immunotherapy for the treatment and prevention of Alzheimer's disease has sparked an interest in utilizing the same approach for other forms of aging damage, including the clearance of pathological tau species from within neurons. A group led by Dr. Lars Ittner of the University of Sydney has recently published promising results from studies using a vaccine targeted at the neurofibrillary tangles (NFTs) that are characteristic of established tau accumulation.
APBs - protein complexes associated with telomeric DNA in ALT (Alternative Lengthening of Telomeres) cancer cells - are the leading candidates for the sub-cellular site at which the ALT mechanism occurs. Recent work involving the generation of artificial APBs has shed light on their composition and function, providing hints as to how ALT might be disabled.
With True Cells Come True Benefits: the Potential of Human Pluripotent Stem Cells Released in a Model of Parkinson's DiseasePosted by Michael Rae on November 24, 2011 | Chief Science Officer's Team
Parkinson's disease is characterised by the loss of dopaminergic neurons from the substantia nigra, and cell therapy is being actively pursued as a means to replace the losses. Most trials to date have used fetal tissue, an approach that although transiently effective is unscalable and prone to immune rejection. Human dopaminergic neurons differentiated from stem cells have historically had poor therapeutic efficiency, but a new study using an improved differentiation protocol has shown much more positive results.
"Senescent" cells progressively restrict the body's capacity for tissue renewal and secrete factors that disrupt local tissue homeostasis. A new study provides proof-of-concept that ablation of these cells can delay - and potentially contribute to the reversal of - age-related tissue dysfunction and disease.
Aggregates of beta-amyloid protein (Abeta) and other malformed proteins accumulate in both "normal" brain aging and neurodegenerative disease, leading to neuronal loss. Their removal by immunotherapy is a central plank of the SENS platform, and the most clinically advanced. Gantenerumab, a new fully human anti-Abeta monoclonal antibody, has just completed a Phase I trial.
The elimination from the body of telomerase, the enzyme used by most cancer cells to maintain their DNA through unlimited numbers of cell divisions, is the central component of the WILT (Whole-body Interdiction of Lengthening of Telomeres) strategy proposed by SENS Research Foundation as a universal and unbreachable defence against all forms of cancer. Concerns have been raised, however, that telomerase may have other biologically important functions, making its elimination dangerous or impossible. Fortunately, recent work by Nobel laureate Carol Greider indicates a lack of any such activity.
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.