The SENSible Blog discusses the development of rejuvenation biotechnology around the world: progress being made in the field of longevity, the design of medical therapies to cure, reverse and prevent the diseases and disabilities of aging, and much more.

Our content is a blend of popular interest articles – labelled “Easy Reads”, and designed to require no specific background knowledge – as well as more detailed scientific commentaries, labelled as “In-Depth” and aimed towards readers with some grounding in the biological/medical sciences.

In-Depth

Abeta Clearance Removes Early Tau Pathology in Neuronal Processes

The clearance of beta-amyloid (Abeta) and other protein aggregates by immunotherapy is a key rejuvenation biotechnology to restore youthful function to aging brains, especially those with Alzheimer’s disease (AD) and other neurodegenerative disorders. Initial trials using anti-Abeta vaccines have demonstrated concomitant reductions in early-stage tau aggregates, but not in mature neurofibrillary tangles, suggesting that such vaccines would be optimally deployed much earlier in the disease process – or in combination with anti-tau vaccines.

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In-Depth

Progress in Targeting Tau Pathology

Neurofibrillary tangles (NFTs – cytoplasmic inclusions composed of abnormal species of tau protein) accumulate in the aging brain, particularly in neurodegenerative disease, where they are closely associated with areas of neuronal death. The urgency of tackling tau accumulation in particular has become more apparent after recent studies revealed that clearance of beta-amyloid alone achieves only moderate clinical benefits, with continued pathology attributed in particular to persistent NFTs.

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In-Depth

New SENS Foundation-Funded Research Project: Catalytic Cleavage of Age-Related Cardiac Amyloid

The well-known beta-amyloid protein that plays a major role in Alzheimer’s disease is only one of those which accumulate in aging bodies. Cardiac amyloidoses, caused by aggregation of the proteins transthyretin and atrial natriuretic peptide, are already the dominant cause of death in supercentenarians (those 110 years of age or older) and are expected to become much more widespread in an increasingly aged general population and as improved treatment options become available for other age-related diseases. SENS Research Foundation has recently launched a project exploring the use of catalytic antibodies – which actively degrade their target, rather than merely binding to it – to remove such aggregates.

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In-Depth

A New TALE for Targeting Genes

A technique combining the sequence-specific DNA-cleaving property of zinc finger nucleases (ZFNs) and the localisation function of transcription activator-like effectors (TALEs), creating a new class of composite proteins called TALE nucleases (TALENs), shows considerable promise for expanding the range of genomic sites susceptible to precision engineering.

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In-Depth

Optimizing Abeta Clearance with Catalytic Immunoglobulins

Comprehensive rejuvenation must include the removal of extracellular protein aggregates from aging tissues. Immunotherapy – in which the immune system is encouraged to recognise and clear a particular protein – is the most clinically-advanced biotechnology for this purpose, but has some limitations. Notably, rapid immune clearance of a large volume of protein can cause severe inflammatory side-effects; also, efficacy depends on the patient’s response to vaccination, which declines dramatically in the elderly patients most in need of therapy. A new approach using catalytic antibodies that directly degrade the amyloid proteins may overcome these problems.

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In-Depth

Early Advance Toward Allotopically-Expressed Mitochondrial RNA

Mutations to the mitochondrial DNA (mtDNA) are thought to be a major source of aging-related increases in oxidative stress. The candidate SENS therapy, allotopic expression, involves the production of mitochondrial proteins from the nuclear DNA and their import into the organelle. An alternative mechanism where RNA, rather than protein, is imported is now providing another avenue for research.

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