A Nature study published in late July 2026 links mitochondrial metabolism to the SASP-driven chronic inflammation that accompanies aging, tying senescent cells’ metabolic activity to tissue dysfunction.

Senescent cells stop dividing but stay metabolically active, secreting inflammatory molecules that drive tissue dysfunction and disease as we age.

The research was funded by NIH institutes, the DoD, Hevolution Foundation, The Glenn Foundation, Cancer Research UK and others, with the study DOI 10.1038/s41586-026-10791-2.

In aging mice, CTPI-2 treatment reduced inflammation across tissues and improved tissue function and healthspan, though immune signaling from mitochondrial leakage persisted and human safety remains unestablished.

CTPI-2 blocks a transporter required for acetyl-CoA production, thereby reducing SASP activity, suppressing inflammation, and improving tissue function and healthspan in aging mice.

CTPI-2 reduces SASP-related inflammation by limiting chromatin opening without broadly suppressing immune signaling.

Disrupting the metabolic signal with CTPI-2 lowers SASP activity and inflammation while enhancing tissue health in aging mice.

The study identifies a two-pathway mitochondrial mechanism: increased acetyl-CoA from altered metabolism opens chromatin near SASP genes, and damaged mtDNA/RNA leaks into the cytoplasm to activate immune signaling that promotes SASP transcription.

Senescent mitochondria produce more acetyl-CoA, loosening histone spools around DNA and making inflammatory genes more accessible for transcription without changing the DNA sequence.

Inflammatory signaling from damaged mitochondria (leaky mtDNA/RNA) works with acetyl-CoA–driven accessibility to drive SASP gene transcription.

The findings point to a therapeutic strategy for mitigating age-related inflammation by targeting metabolic signals that regulate DNA accessibility, potentially slowing functional aging.

Blocking the metabolic signal can dampen SASP even when mitochondrial immune signaling persists, suggesting a novel approach to reduce age-related inflammation.