New 'Pasta' Aging Clock Finds Drug Candidates That Rejuvenate Human Cells

The work, published in Advanced Science in 2026, is laboratory and computational research. It did not test any treatment in people or animals. The team trained the tool on 17,212 healthy human samples from 21 studies, then applied it to existing datasets and ran cell experiments to check two of its findings.

The tool is called Pasta, short for Predicting Age-Shift from Transcriptomic Analysis. It is a transcriptomic aging clock. That means it estimates how old a sample is biologically from which genes are switched on, rather than from the calendar. Earlier clocks of this kind often worked only in one tissue or on one lab platform, or were hard to obtain, according to the authors.

Pasta uses what the authors call an age-shift approach. Instead of guessing an exact age, the model learns to tell which of two samples is older when they are about 40 years apart. In the authors' tests, this design gave the best results among the approaches they compared. They tested each model on whole datasets it had never seen during training.

According to the paper, Pasta worked on bulk RNA sequencing, single-cell RNA sequencing and microarray data. It predicted relative age best in 6 of 8 datasets in the team's held-out analysis, and in 4 of 6 independent validation datasets, when compared with two leading multi-tissue clocks, MultiTIMER and tAge. It also predicted age in mouse tissues. In a reproducibility test across six laboratories, 98.8% of the variation in Pasta scores came from the samples themselves rather than from the site.

The genes the model relied on were enriched for p53 signalling and the DNA damage response. These are pathways involved in how cells react to damage. Pasta scores also lined up with senescent cells, which have stopped dividing, and with stem-like cells. In several cancer types, higher Pasta scores correlated with tumor grade and patient survival. These are associations, and the paper does not show that the scores cause those outcomes.

The team then applied Pasta to more than three million transcriptomes from the Connectivity Map L1000 dataset. These records show how cell lines respond to thousands of drugs and genetic changes. Pasta flagged both known and previously unrecognized compounds and genetic changes that shift apparent age. According to the authors, mitochondrial translation was a key factor in a cell's tendency to age, and mRNA splicing in its tendency to rejuvenate.

Two findings were tested in human cells. The cancer drug pralatrexate was confirmed as a potent inducer of senescence. Piperlongumine acted as a rejuvenating agent. The study reports no effect sizes for these experiments, and a younger-looking gene activity pattern in a dish is not the same as better health in a person.

For now, the practical value is in drug discovery. A clock like this could help researchers choose which compounds deserve closer study, and could also flag agents that push cells toward senescence, which might matter in cancer research. The authors describe Pasta as a tool for aging research and therapeutic discovery. They do not present piperlongumine or any other compound as something people should take.

What to watch next

Whether the piperlongumine result holds up in other cell types and in animal studies, and whether other groups confirm Pasta's predictions.

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