Overlooked biology, newly on show at nuupeptide
“Nuu” suggests something new. I’d give the wall space to a capability that was here all along: a heart making ketones, or a peptide encoded in familiar DNA.
Ketone-making in the heart
The heart’s own capacity to make ketones is an excellent reason to look again at a familiar organ. A 2025 study of human myocardium and a mouse heart-failure model examined that capacity through HMGCS2, an enzyme involved in making ketones. In the mouse model of heart failure with preserved ejection fraction, NAD+ repletion restored HMGCS2 activity through deacetylation, increased fatty acid oxidation and rescued cardiac function. Reducing HMGCS2 in heart muscle cells prevented the rescue.
I had pictured simple replenishment. The dependence on a particular piece of cardiac machinery is much more absorbing. It gives the proposed effect an address and a condition: this mechanism had to be available. The functional rescue came from mice; the human tissue work gives the experiment human relevance without supplying a treatment result in patients.
That discovery earns its place at nuupeptide. An existing organ turns out to have an underappreciated capability, and the experiment changes the questions worth asking about it.
Mitochondrial DNA
MOTS-c offers another reason to revisit something familiar. Its 16-amino-acid sequence is encoded within the mitochondrial 12S ribosomal RNA gene. A stretch of genetic material associated with ribosomal RNA also contains the instructions for a small biologically active peptide. I enjoy that economy: familiar territory, another function.
The CK2 experiments in cell-free systems and mice give that peptide a direct molecular target, with different CK2 effects in muscle and fat. The MOTS-c page follows the sequence, those tissue differences and the human observations. The NAD+ molecule page starts from chemistry: a dinucleotide that transfers electrons and supplies enzymes with a substrate.
Human measurements
A discovery can be fascinating while its practical reach remains small. In prediabetic, postmenopausal women given oral NMN, muscle insulin sensitivity improved, while body composition and HbA1c stayed unchanged. I’d hang that selective result on its own: it identifies a change and leaves other measurements where they were.
The 2025 review of human NAD+ precursor trials describes limited efficacy and sparse information about tissue-specific NAD+ dynamics. For MOTS-c, human findings include an observational cohort of chronic hemodialysis patients; human intervention results for administered MOTS-c are still missing. NAD+ vs MOTS-c puts those different kinds of findings beside each other. The questions page deals with the practical queries that tend to follow.