Imagine: not only living longer, but living well for longer. Staying fit into old age. Clear-headed. Keeping energy for the things that matter. That is what longevity is about, and it is no longer science fiction.
At Dutch Balance we follow the science closely. Not because we believe in miracle cures, but because we want to understand what really works. In this article we share what we know about ageing: why it happens, which researchers are shaping the field, and what you can do today. Honestly, without exaggeration, with an eye for what is proven and what is not yet.
What is longevity?
Longevity literally means ‘long life’. But within science the meaning has become more specific. It is not only about more years, but about more healthy years.
Researchers distinguish between two terms. Lifespan is the total number of years you live. Healthspan is the number of years you live healthily and functionally, free of chronic illness or limitations. The aim of longevity research is to narrow the gap between the two. To make sure the extra years we gain are good years too.
Doctor and longevity expert Peter Attia describes the core problem of modern medicine as follows: we often treat too late, when diseases are already manifest. His argument, which he calls “Medicine 3.0”, is to work proactively on health rather than reactively treating disease. Prevention rather than cure. That appeals to us.
Why do we age? The 12 hallmarks of aging
In 2013 researchers Carlos López-Otín and colleagues published a groundbreaking article in the scientific journal Cell. They identified nine fundamental characteristics of ageing at cellular level. In 2023 this framework was expanded to twelve characteristics, the so-called hallmarks of aging.
To qualify as a hallmark, a process must meet three criteria: it manifests with increasing age, accelerating it experimentally accelerates ageing, and therapeutic intervention can slow, stop or reverse ageing.
The primary hallmarks are the direct causes of cell damage. Think of genomic instability (accumulation of DNA damage), telomere shortening (the protective end caps of your chromosomes get shorter with every cell division), epigenetic changes (disruptions in which genes are active), loss of proteostasis (the clean-up system for proteins works less well) and disabled macroautophagy (the cellular ‘clean-up service’ functions worse).
Then there are the antagonistic hallmarks: responses to damage that are initially protective, but become harmful later. These include deregulated nutrient sensing, mitochondrial dysfunction (the power stations of your cells work less efficiently) and cellular senescence, the accumulation of ‘zombie cells’ that no longer divide but do not die off either.
Finally the integrative hallmarks: consequences that manifest at tissue level. Stem cell exhaustion, altered communication between cells, chronic low-grade inflammation (also called ‘inflammaging’) and dysbiosis, the disruption of your gut flora.
Why is this framework so valuable? Because it gives direction. If we understand why we age at cellular level, we can look more precisely for interventions that do something about it.
NAD+ and sirtuins: your cells’ energy household
One of the most researched routes in longevity science is the role of NAD+, in full nicotinamide adenine dinucleotide. This molecule is involved in hundreds of cellular processes, from energy production to DNA repair.
NAD+ is essential for the functioning of sirtuins, a family of enzymes that are regarded as ‘longevity proteins’. Sirtuins play a role in the production of new mitochondria, DNA repair, suppressing cellular senescence and regulating inflammatory processes.
The problem: NAD+ levels decline with age. By the age of fifty you have, by some estimates, only half the NAD+ levels you had at twenty. That means sirtuins can function less effectively.
Researchers have therefore paid a lot of attention to NAD+ precursors: compounds your body can convert into NAD+. The best known are NR (nicotinamide riboside), a form of vitamin B3 that is efficiently converted into NAD+, and NMN (nicotinamide mononucleotide), a more direct precursor.
In animal research these precursors show promising results. Human research is still ongoing and the results are mixed so far. This is important to know: promising is not yet proven. What we do know is that exercise, fasting and good sleep help keep NAD+ levels up naturally.
The Information Theory of Aging
Harvard geneticist David Sinclair has formulated an influential theory about the fundamental cause of ageing. His “Information Theory of Aging” holds that ageing is primarily caused by the loss of epigenetic information.
Sinclair uses a clear metaphor for this: see your DNA as a CD with all the music you need. Your epigenome is the CD player that determines which tracks are played. Over the years the CD player gets damaged, scratches appear as it were, so the wrong tracks are played.
The hopeful thing about this theory: the original information is still intact. If we can repair the ‘scratches’, ageing would in principle be reversible. In 2020 Sinclair’s lab published research in which they reversed blindness from glaucoma in mice using special proteins. In 2023 they replicated this in monkeys. The research is still at an early stage, but the implications are fascinating.
The pioneers of longevity research
The longevity field is shaped by a diverse group of researchers, doctors and entrepreneurs. A few names you should know.
David Sinclair is professor of genetics at Harvard Medical School and director of the Paul F. Glenn Center for Biology of Aging Research. He is known for his research into sirtuins and NAD+. His book Lifespan: Why We Age – and Why We Don’t Have To brought longevity science to a wide audience. One note: Sinclair has commercial interests in companies that produce NAD+ supplements. That does not necessarily make his research unreliable, but it is worth knowing.
Peter Attia is a doctor and founder of Early Medical, a practice focused on the science of longevity. He is known for his data-driven approach. His book Outlive: The Science and Art of Longevity became a number 1 New York Times bestseller. Where Sinclair focuses on molecular mechanisms, Attia focuses on what he calls the “Four Horsemen”: the four diseases that kill most people: heart disease, cancer, neurodegenerative conditions and type 2 diabetes. His podcast The Drive is, with more than 100 million downloads, one of the most popular health podcasts in the world.
Andrew Huberman is a neuroscientist at Stanford University and host of the Huberman Lab Podcast. He does not focus specifically on longevity, but his ability to make complex neuroscientific concepts accessible has made him enormously popular.
Bryan Johnson is the tech entrepreneur who made his fortune with the sale of Braintree to PayPal. He is known for his “Blueprint” project: a protocol of more than 100 supplements, strict eating schedules and medical interventions. Johnson is controversial. Critics point out that his approach is extreme and achievable for virtually nobody. Supporters appreciate his transparency. His motto “Don’t die” sums up his philosophy.
Carlos López-Otín is a Spanish biochemist and lead author of the influential “Hallmarks of Aging” papers. Less well known to the general public, but his work forms the scientific basis of the whole field.
Promising interventions: what is being researched?
In 2024 Leonard Guarente, David Sinclair and Guido Kroemer published an overview in Cell Metabolism of interventions being investigated in human trials. Important note: “investigated” does not mean “proven effective”.
The eight most researched interventions are metformin (a diabetes medicine that activates AMPK), NAD+ precursors such as NMN and NR, GLP-1 agonists such as Ozempic, rapamycin (an immunosuppressant), spermidine (a natural compound that stimulates autophagy), senolytics such as fisetin and quercetin (compounds that clear out zombie cells), acarbose (slows carbohydrate absorption) and SGLT2 inhibitors.
These are not recommendations. Many of these substances are medicines with side effects that require medical supervision. We mention them to give a complete picture of where the research stands.
What can you do yourself?
The good news: the most powerful interventions for a long and healthy life are not pills or supplements. They are lifestyle factors you can start with today.
Exercise is perhaps the most powerful intervention. Research shows time and again that VO2 max, your maximum oxygen uptake, is one of the strongest predictors of life expectancy. Muscle mass protects against metabolic disease and falls in later life. Exercise activates autophagy and raises NAD+ levels naturally.
Nutrition makes an enormous difference. Avoid ultra-processed food. Make sure you get enough protein, especially in later life. Eat plenty of vegetables and fruit because of the polyphenols. Periodic fasting can stimulate autophagy and sirtuin activity, although this is not suitable for everyone.
Sleep is not negotiable. Sleep deprivation accelerates virtually all hallmarks of aging. Aim for seven to nine hours of quality sleep a night. Bryan Johnson, despite all his interventions, calls sleep his number one priority.
Stress management deserves more attention than it often gets. Chronic stress raises cortisol and inflammatory markers. Meditation, breathing exercises and time in nature can help regulate stress.
Social connection is perhaps the most underrated factor. Loneliness is associated with increased mortality, comparable with smoking. The Blue Zones, regions where people live exceptionally long, all have strong social networks in common.
Supplements: what does the science say?
Let us be honest: supplements are no replacement for a healthy lifestyle. They can support it. Here is an honest overview of what we know about the most popular longevity supplements.
Nicotinamide riboside (NR) raises NAD+ levels in the blood. It has been found safe in human studies. The effect on actual lifespan has not been proven, but the mechanisms are promising.
TMG (betaine) is a methyl donor that is often combined with NAD+ precursors to top up methyl groups.
Trans-resveratrol is a sirtuin activator, known from red wine. Promising in animal research, but the human evidence is still weak.
Quercetin is a flavonoid being looked at in research because of possible senolytic properties, in other words clearing out aged cells.
Berberine is a plant extract that research links to AMPK. It is sometimes called “natural metformin”.
We are honest: there is no supplement that has been proven to extend human lifespan. The mechanisms are plausible, the animal research is promising, but the definitive evidence is still missing. See supplements as an addition to the fundamentals: exercise, nutrition, sleep, stress management and social connection. Not as a replacement.
At Dutch Balance we offer a selection of these supplements, not because we promise they extend your lifespan, but because the science behind them is interesting enough to consider them as part of a broader approach. We believe in honest information, so you can make a well-considered choice yourself.
The future of longevity
David Sinclair predicts that within a decade we will have pills that significantly slow the ageing process. That is a bold claim and time will tell whether he is right.
What we can say is that the science is making progress. We understand better and better why we age and which dials we can turn. The twelve hallmarks of aging give researchers a roadmap. The first medicines are being tested in human trials.
But the fundamentals remain unchanged. Exercise, good nutrition, enough sleep, stress management and social connection: these pillars will probably always matter more than any pill or supplement.
Longevity is not about living forever. It is about living well, for as long as possible. And you can start with that today.
Do you have questions about longevity or our supplements? Feel free to get in touch. We are happy to help.
Frequently asked questions
What does longevity mean?
Longevity literally means ‘long life’, but in science it refers to both lifespan and the number of healthy years. The aim is not only to live more years, but more good-quality years.
Is ageing a disease?
This is a debate within the field. Researchers such as David Sinclair argue for seeing ageing as a treatable condition, because it is the underlying cause of most chronic diseases. Formally the WHO does not yet classify ageing as a disease.
Do longevity supplements really work?
There is no supplement yet that has been proven to extend human lifespan. There are supplements with plausible mechanisms and promising animal research. The most important longevity interventions remain lifestyle factors: exercise, nutrition, sleep and stress management.
How can I measure my biological age?
There are tests based on DNA methylation that give an estimate of your biological age. The best known are the Horvath clock and GrimAge. These tests are getting more accurate, but do not yet tell the whole story.
