Aging
An independent computational project. I suspect aging, more than damage, is what stops mammals from regenerating. This asks whether the nucleus and the mitochondria drifting out of balance turns the regeneration program down. Scroll to go inside the cell. Drag the model, hover any part.
does aging switch off regeneration?Mitochondria are built from two sets of DNA
Each mitochondrion carries its own tiny genome, which encodes just 13 proteins. Nuclear genes encode the rest, so the nucleus and the mitochondria have to stay in step.
Orange dots: proteins sent in from the nucleus. Charcoal dots: signals reporting back.
Mitonuclear imbalance
The idea: with age the two sides drift apart. Mitochondria fragment and dim, and the conversation between nucleus and mitochondria falls out of sync. Watch the flow stutter. This scene is a schematic.
A gene signature that fades
I tracked a regeneration gene signature in human tissue and asked how it relates to mitonuclear imbalance. In brain, liver and heart, the more imbalance, the lower the signature.
NAMPT controls the NAD+ supply
NAD+ fuels mitochondria and the sirtuin enzymes. Cells make it by recycling nicotinamide, and NAMPT is the rate-limiting step. My analysis flags NAMPT as a druggable chokepoint gene, and points to nicotinamide and NMN, which feed the same pathway.
As the gate narrows, precursors pile up and less NAD+ reaches the mitochondria.
The effect depends on the tissue
I used GTEx data (via recount3) across five human tissues. The effect is tissue-specific: suppressive in brain, liver and heart, and reversed in skin. Four of the five are shown here.
What this does not show
This is a computational analysis of public bulk-tissue data. It shows association, not cause. Nothing here was tested in cells or animals, and the 3D scenes are schematic illustrations, not microscope images.