The cell’s power and repair
Vincenzo Sorrentino is an aging biologist at the National University of Singapore, part of the city’s remarkable longevity cluster around Brian Kennedy. His science sits where the cell makes its energy and keeps its proteins in order — mitochondria, energy metabolism, and the quality control that stops proteins from misfolding as we age.
He first made his name showing that “energy boosters” — interventions that improve mitochondrial function — could reduce age-associated amyloid, the sticky protein aggregates of aging, even in the muscles of old mice. That points to a bigger idea he is chasing now: catching protein aggregation before it becomes disease, and finding compounds that help cells fold, clear and repair.
It is patient, mechanistic work, and he is refreshingly open about the path from lab to life: screen candidates in worms, validate the best in mice, and — ideally using drugs already in the FDA library — work out whether they can help humans. Much of this he does hand-in-hand with his friend and collaborator Jan Gruber, whose worm-screening platform pairs neatly with Vincenzo’s biology.
What stayed with us on the walk was his spirit about the whole endeavour. Aging, he says, is complex but fascinating — a live discovery that everyone can take part in, not just a handful of scientists. It needs biologists, engineers and ordinary people to learn about it and talk about it together.
He did not drift to Singapore. He wrote to Brian Kennedy. Vincenzo is not a physician — he is a basic scientist, and after four years working inside a company he had come to want something specific: a way to get what basic science discovers to people faster. When he heard that Brian had created the Healthy Longevity Translational Research Programme at NUS, co-directed by Andrea Maier, he contacted him and said so plainly — if I can bring my ideas here, execute them, and work with clinical teams to translate them, that would be really great.
What he says he watched for in Brian was not the science. It was how he handles the people around him: not only achieving what he needs to achieve for himself, but making sure the people who work for him grow into independent scientists. That is the thing Vincenzo says he wants to be able to do with his own team.
His own subject is NAD — a coenzyme almost every process in the body depends on, which falls away in some tissues with age and in certain metabolic conditions. Keep the levels up in the places that need them, and you can delay or soften what follows. The whole family of NAD boosters works by being precursors: they are not NAD, they are turned into it, and different ones take different routes through the body, which is why the useful question is not which is cheapest but which one suits the organ you are worried about.
And in this conversation, in October 2023, he described a new one he had not yet published. Made largely in plants; taking the Preiss-Handler pathway rather than the salvage pathway that NMN and NR use; stable enough in blood to reach the brain, the liver and the muscle; and already higher in people who drink coffee or eat a vegetarian diet. Five months later it was published in Nature Metabolism as trigonelline — an NAD+ precursor that improves muscle function in ageing and is depleted in human sarcopenia. He never names it here. He is telling two visitors about a discovery before the world has it.
The second line of his work is stranger and, to us, more startling. Everyone associates amyloid with Alzheimer’s. What his earlier work showed is that ordinary ageing muscle, in otherwise healthy animals and people, starts forming the same kind of protein aggregates — amyloid seeds, he calls them, which he suspects predispose to disease later. And that raising NAD or improving mitochondrial function can clear them. So his question at NUS is: which proteins do this, and can we get rid of them before anything has gone wrong?
