Category: Blog

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.

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.

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.

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.

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.