The first years of CHARTAGING have already yielded discoveries that are reshaping how scientists think about ageing, with results published in journals including Cell and Nature Cell Biology.
One of the team’s first tasks was methodological: to develop tools capable of reading the molecular state of tissues not as a list of cells, but as a map. Using a state-of-the-art platform, the team can now measure the activity of thousands of genes in each individual cell — while keeping every cell pinned to its exact location within the tissue. The result is something like a Google Maps of ageing biology: a richly detailed, navigable atlas in which you can zoom from the whole organ down to a single cell and ask what it is doing, who its neighbours are, and how all of this changes over a lifetime. The team is now building the first comprehensive spatial portraits of how tissues deteriorate.
These maps have already produced a striking finding: when YAP and TAZ go silent in the connective tissue cells of an ageing organ, those cells trigger a molecular alarm that was never meant to fire. A surveillance system called cGAS/STING — the body’s internal detector for viral invasions — gets activated by mistake, mistaking signals from the cell’s own deteriorating machinery for signs of infection. The result is a smouldering, chronic inflammation that poisons the tissue from within, pushing cells into a state scientists call senescence: they don’t die but linger, leaking toxic signals that accelerate the ageing of everything around them. The team has now shown, across several organs and experimental models, that switching off this misfiring alarm is enough to dramatically slow tissue ageing. A particularly exciting frontier the team is now actively pursuing is female reproductive ageing. The ovary is one of the earliest organs to age in mammals, and its decline has far-reaching consequences for health well beyond fertility — from cardiovascular risk to bone loss to metabolic disease. The question CHARTAGING is now asking is whether the same inflammation-driven, mechanosensing-dependent axis that governs ageing in skin, kidney and aorta also drives the progressive loss of ovarian function. If it does, it would open entirely new possibilities for understanding and one day intervening in one of the most consequential and least understood aspects of female biology. This is among the most ambitious goals of the next phase of the project.
Running in parallel, a study published on the cover of Nature Cell Biology (Vanni, Citron et al., 2025) has addressed a question that sits beneath everything else: how do cells actually feel the world around them? The extracellular matrix, the cytoskeleton inside the cell, and the membrane encasing the nucleus are not separate systems — they form a single continuous tensioned structure, like the strings, body and soundboard of an instrument. Mechanical information flows through this structure as a whole, from the outside world all the way to the DNA. When the matrix ages and loses its integrity, the instrument goes out of tune, the signal breaks down, and YAP and TAZ fall silent. Revealingly, the same structural axis is disrupted in rare genetic diseases that cause dramatically accelerated ageing, confirming that this mechanical chain is not just a laboratory experiment but a genuine guardian of tissue youth.
A further discovery, published in Cell, has uncovered a second antenna system working alongside YAP and TAZ: a family of proteins called ETV1/4/5 that respond by activating a programme of three-dimensional tissue construction — the same programme the embryo uses to build organs in the first place. The team is now exploring how this developmental blueprint is reawakened or lost during ageing and regeneration, and what this means for the body’s capacity to repair itself.
