Research

Project Neurospike: FRO focused on Fast-Spiking Neuron Degeneration (FSND)

Deck is here

Draft of paper to be released to bioarXiv soon

0. Focused Research Organization (FRO)

An FRO is a time-bound, technically ambitious effort designed to produce high-impact public goods that unblock scientific progress.

https://www.convergentresearch.org

A Focused Research Organization (FRO) is a time-limited (3–7 years), mission-driven, non-profit, or startup-structured entity designed to accelerate scientific progress by tackling, mid-scale, "bottleneck" projects. FROs bridge the gap between academia and industry by developing public-good tools, datasets, and infrastructures that are too large for labs and not profitable for companies.

https://fas.org/publication/focused-research-organizations-a-new-model-for-scientific-research

1. Fast-Spike Neurons are Powerful but Fragile

Fast-spike neurons are present throughout our nervous system. They compose a relative minority of neurons but have outsized importance. They are also uniquely fragile and start to degenerate and die early in our lives, as early as our mid-20s. While effects are not so noticeable at first, this early degeneration starts a cascade of failures, both within the nervous system and the body as a whole, so much so that it may be the primary driver of our aging.

Relatedly, fast-spike neurons have high metabolic demands and are difficult to maintain, and so are actively culled at an even faster rate than their intrinsic degeneration if not actively used. This can be seen most commonly with motor neurons. A lack of explosive movement and exercise, which is typical in adult human life, hastens the demise of the high-spike motor neurons that effectuates such movement.

Current medicine and longevity science focuses on “hardware” preservation: the clearing of plaques, preventing muscle atrophy, and keeping cells alive. But this misses the main driver of functional aging. Older adults with perfectly healthy MRI scans and intact muscle mass still suffer from severe physical and cognitive decline due to declining high-spike impetus and control. Thus our hardware remains largely intact into our 60s, but the "software" begins to fail much earlier.

2. The Metaphors: Electrical Brownout & Underclocking

Imagine a building with its own electrical generator. When new, the generator runs flawlessly, supplying perfectly phased alternating current at a constant voltage. As it ages and the parts wear down, phase starts to drift and voltage fluctuates. Simple appliances such as low watt light bulbs and toasters are hardly affected. High-power and precision instruments are susceptible to malfunction and damage, and will simply short out as the generator behavior degrades . We can address such problems with grid synchronizers, surge protectors, and other solutions, but the main problem stems from the degrading generator, which in this metaphor, is the metabolic engine driven by mitochondria and energy metabolism. The degeneration of fast spike neurons effectively leaves the nervous system in an underclocked state– it can generate slow to medium spike rates, but fails at faster ones. This causes the nervous system to fray and fall apart.

Medicine focuses on fixing or replacing the appliances themselves, or at best adding patchwork solutions similar to grid synchronizers. Mitochondrial and metabolic science are just beginning to address the generator and the wiring itself. What is missing, however, is a coherent paradigm to unite all of these efforts into a systemic approach. For decades, we have treated neurological diseases of aging as separate diseases based on anatomical subsystems. And therapeutics target the problems only downstream, addressing the hardware damage left behind by the neural dysfunction (trying to fix the appliances after the fact).

3. The Systemic Paradigm: Fast-Spiking Neuron Degeneration (FSND)

In order to advance efforts in the field, our FRO seeks to unify longevity science efforts under a single conceptual rubric: (FSND). All fast-spiking neurons share a common phenotype and degenerate for similar reasons. Their fast firing rates require massive, continuous energy production to enable rapid ion surges, and related buffering and pumping. As such they exist on a metabolic knife-edge which makes them quite fragile.

The remainder of the Executive Summary is here