🇦🇺David
Sinclair

David Sinclair arrived in Boston in 1995 with a PhD from the University of New South Wales, a fascination with why cells age, and an appointment in the laboratory of Leonard Guarente at MIT — one of the world's leading labs for the study of aging biology. He had grown up in Sydney watching his grandmother suffer the progressive losses of old age and had decided, at an unusually young age, that aging was not an inevitable feature of existence but a biological process — and that biological processes could be understood, and in principle, altered. This was not a popular view in mainstream gerontology at the time. It has since become the governing assumption of one of the fastest-growing fields in science, in no small part because of Sinclair's work.

At MIT, Sinclair made his first major discovery: working with yeast, he found that a gene called SIR2, which encodes a protein from the sirtuin family, played a central role in determining how long the organisms lived. The sirtuins were a family of proteins that had been known for some time but whose function was poorly understood. Sinclair's work, published in 1997, showed that extra copies of SIR2 extended yeast lifespan by up to 30 percent — one of the first demonstrations that a single gene could significantly alter the rate of aging. He moved to Harvard Medical School in 1999, where he has remained, building the Paul F. Glenn Center for Biology of Aging Research into one of the most productive aging laboratories in the world.

The work at Harvard deepened and expanded. Sinclair's lab identified the sirtuins' molecular partner: NAD+, a coenzyme found in every cell in the body that declines dramatically with age and is essential for sirtuin activity. NAD+ became the focus of intense research both in his lab and, eventually, in the broader biotech industry. Studies in mice showed that boosting NAD+ levels with precursor molecules like NMN (nicotinamide mononucleotide) could reverse many markers of aging: improving muscle function, metabolism, cognition, and cardiovascular health in aged animals. Human clinical trials followed. Sinclair himself has been openly self-experimenting with NMN for years — a practice that has made him a celebrated and occasionally controversial public figure.

In 2013, Sinclair's lab published a landmark paper in Cell demonstrating that the decline in NAD+ levels with age impairs the ability of sirtuins to maintain mitochondrial function, and that restoring NAD+ levels could reverse this impairment — effectively making the mitochondria of old mice look more like those of young mice. The paper was described by some scientists as one of the most important aging papers of the decade. It also sparked a wave of interest in NAD+ precursor supplements that has made NMN and NR (nicotinamide riboside) among the most commercially successful longevity interventions.

Sinclair's broader theoretical framework — the information theory of aging — proposes that aging is fundamentally a loss of epigenetic information: the molecular instructions that tell each cell what type of cell it is and how to behave. He argues that DNA damage causes the epigenome to become scrambled over time, so that cells increasingly lose their identity and function. His lab has demonstrated in mice that this process can be partially reversed using the Yamanaka factors — a set of genes that can reprogram cells — to restore the epigenome to a younger state. In a 2023 paper that provoked enormous scientific debate, his lab reported being able to measurably age and reverse-age mice at will by manipulating these factors. The implications, if the work holds, are radical.