Michael Rae

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.

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.

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.