Science: Die Biologie des Alterns

Research into aging is advancing fast. The consumer version of it (the clocks, the supplements, the off-label drugs) promises far more than anyone has actually shown will help a person live longer.

What Aging Is

Aging runs through at least twelve cellular and molecular processes at once, and they build up together and reinforce each other. At the tissue level this shows up as slower repair and a growing load of damaged cells the body no longer clears. A low, steady background of inflammation rises with the years, sometimes called inflammaging. Because so many processes change together, any single intervention can only do so much.

No single treatment resets the whole system, and changing one process tends to affect the others, for better and worse. Much of aging works through mitochondria, the recycling process of autophagy, and the controlled-stress pattern of hormesis.

The Hallmarks

Most researchers now organize aging around the hallmarks of aging. A 2013 review named nine, and a 2023 update expanded the set to twelve shared processes:

• genomic instability, accumulating DNA damage
• telomere attrition, the shortening of chromosome end-caps
• epigenetic alterations, drift in the chemical marks that control what a cell is
• loss of proteostasis, failing protein quality control
• disabled macroautophagy, weaker cellular recycling
• deregulated nutrient sensing
• mitochondrial dysfunction
• cellular senescence, the build-up of worn-out cells that will not divide or die
• stem cell exhaustion
• altered intercellular communication, including chronic inflammation
• dysbiosis, a disordered gut microbial community

The list groups the biology; the causal order among the hallmarks is still unconfirmed. They are tangled together and reinforce each other, so no one of them is the single root cause.

Chronological Versus Biological Age

Chronological age is the simple count from your birth date. Biological age estimates your body's condition from measurable markers, and the two can differ. Two people born the same week can be years apart on the cellular measures. Someone whose body is aging faster than their birthdays suggest carries more disease risk; someone aging slower carries less. That gap is what biological-age measures try to capture.

Biological age has to be inferred from proxies; there is no single measurement that reads it directly. The best-known proxy is the pattern of chemical tags on DNA, which is what the aging clocks read.

Aging Clocks

The epigenetic clock reads DNA methylation, small chemical tags on the genome, at a few hundred sites, then uses a formula to turn those readings into an age estimate. The 2013 method fitted methylation at 353 sites and estimated a person's age across most tissues to within a median of about 3.6 years. So a biological-age test gives you an estimate of your age built from that formula, plus how far the estimate sits above or below your real age.

People whose clock reads older than their birthday are, on average, more likely to die in follow-up. Later clocks, GrimAge and DunedinPACE, were built to predict health outcomes directly, and they predict mortality, heart disease and disability better still.

No clock has been shown to be a dial you can turn: lowering the number has never been proven to add years.

The marketing claims run ahead of this. The most cited age-reversal result comes from a study of nine men with no control group, in which four clocks read about 1.5 years younger after a year. With so few participants and no comparison group, a real change can't be told apart from ordinary fluctuation, or from the tendency of extreme readings to drift back toward average on their own.

The clocks also disagree with each other. When CALERIE, the main human trial of eating less, applied a methylation panel, the readings split. One pace-of-aging measure, DunedinPACE, slowed slightly. Three age clocks, Horvath, Hannum and PhenoAge, did not move on the same blood samples. A consumer test rests on one such reading, and the "reverse your age" claims attached to these clocks are not established in humans.

What Slows Aging

The strongest evidence for a longer, healthier life points to ordinary habits. In two large US cohorts followed for decades, five basic habits set the groups far apart: not smoking, a healthy weight, regular movement, moderate drinking and a good diet. Adults with all five had a projected life expectancy at 50 about 12 years longer for men and 14 years longer for women than those with none.

Cardiorespiratory fitness shows one of the steepest associations in the literature. Pooling 33 studies and 102,980 people, each step up in fitness tracked with about 13% lower risk of death from any cause and 15% fewer cardiovascular events. One step is a MET, roughly the jump from sitting still to a brisk walk, and the benefit kept climbing with no clear cut-off.

These habits act on the same hallmarks the drugs target:

• Exercise improves mitochondrial function and prompts autophagy.
• Keeping muscle counters the tissue loss that marks aging.
• Not smoking removes a direct source of genomic damage.
• Sleep and a good diet act on nutrient sensing and inflammation.

Much of the metabolic damage these habits reverse is manufactured. In a controlled NIH trial, 20 adults ate about 500 more calories a day on an ultra-processed menu than on a whole-food one matched for calories and macronutrients (Hall 2019). They gained weight in two weeks; on the whole-food weeks, they lost it.

Almost all of this evidence is observational. It shows what goes along with slower aging, without proving cause. The habits also cluster with education, income and access to care, and those advantages lengthen life on their own. The direction is consistent across studies; the exact number of years any single habit adds is beyond what an observational design can settle.

The Anti-Aging Drugs And Supplements

The drugs and supplements sold as anti-aging are mostly early-stage, tested in animals or small pilots of cellular markers. Caloric restriction, eating fewer calories without going short on nutrients, is the most reproducible lifespan-extending intervention in laboratory biology, working from yeast to mice. In rhesus monkeys it delayed age-related disease. In people, the largest controlled trial, CALERIE, randomized 218 healthy adults to cut intake, about 12% in practice. Over two years it improved LDL cholesterol, blood pressure, C-reactive protein and insulin sensitivity. It tracked those risk markers; it never measured lifespan.

The individual molecules are earlier still:

• Rapamycin extends lifespan in mice even when started late in life, repeatably and in both sexes. In people it is an immunosuppressant with side effects and has not been shown to lengthen healthy life.
• Metformin has a plausible biological mechanism, and population studies hint that diabetics taking it may age better. It is now being tested in the TAME trial, which has not reported an anti-aging outcome.
• Senolytics clear senescent cells. They have reached people only in tiny pilots: a short course of dasatinib plus quercetin lowered senescent-cell markers in nine people, with no control group and no health outcome measured.
• NAD precursors such as NMN lift NAD levels in small human studies, with no shown effect on aging.

All remain in trials for slowing aging in a healthy person, whatever the marketing implies.

The Research & Studies

Everything here is based on the research we have collected and checked, sorted into groups and ordered with the strongest evidence first. Click any claim to open the studies behind it.

Longevity And Mortality

Eating less extends lifespan from yeast to mice and delays disease in monkeysEstablished

In plain terms

Eating fewer calories without malnutrition extends lifespan across many species and delayed age-related disease in monkeys.

In detail

Caloric restriction is the most reproducible lifespan-extending intervention in laboratory biology, working from yeast to worms to mice. In rhesus monkeys, long-running studies found reduced age-related deaths and delayed diabetes, cancer and cardiovascular disease, though design differences between two centers affected the all-cause mortality signal.

Who this may not transfer to:Measured in laboratory animals and monkeys; an effect on human lifespan is not established.

The studies · 3

Colman 2009, Science · Science

Colman 2014, Nature Communications · Nat Commun

Mattison 2017, Nature Communications · Nat Commun

Rapamycin verlängerte die Lebensdauer bei Mäusen, auch wenn es spät im Leben begonnen wurdeEmerging

In plain terms

Rapamycin verlängert die Lebensdauer bei Mäusen, auch wenn es spät im Leben begonnen wird, ist aber ein Immunsuppressivum, das beim Menschen keine Verlängerung des gesunden Lebens gezeigt hat.

In detail

Bei genetisch heterogenen Mäusen verlängerte ab 600 Lebenstagen verabreichtes Rapamycin die mediane und maximale Lebensdauer in beiden Geschlechtern. Das Ergebnis ist real und in Mäusen reproduzierbar. Beim Menschen wird Rapamycin als Immunsuppressivum mit Nebenwirkungen verwendet und hat keine Verlängerung des gesunden Lebens gezeigt.

Who this may not transfer to:Measured in mice; a healthy-human lifespan effect is not established.

The study · 1

Harrison 2009, Nature · Nature

Fünf gesunde Gewohnheiten fügten Männern etwa 12 Jahre und Frauen 14 Jahre hinzuModerate

In plain terms

Erwachsene mit fünf grundlegenden gesunden Gewohnheiten lebten in zwei großen Kohorten etwa ein Jahrzehnt oder mehr länger als diejenigen ohne diese.

In detail

In der Nachbeobachtung zweier großer US-Kohorten über Jahrzehnte hatten Erwachsene, die nicht rauchten, ein gesundes Gewicht hielten, körperlich aktiv waren, mäßig tranken und gut aßen, eine projizierte Lebenserwartung im Alter von 50 Jahren von etwa 12 Jahren mehr für Männer und 14 Jahren mehr für Frauen als diejenigen ohne diese fünf. Das Design ist beobachtend.

The study · 1

Li 2018, Circulation · Circulation

Progress Markers

Each 1-MET fitter tracks with about 13% lower death rateStrong

In plain terms

Higher cardiorespiratory fitness tracks with a large drop in death rate, one of the steepest signals in the whole literature.

In detail

Eine Meta-Analyse mit 33 Studien und 102,980 Teilnehmern fand, dass jeder 1-MET-Anstieg der kardiorespiratorischen Fitness mit etwa 13 % niedrigerer Gesamtmortalität und 15 % weniger kardiovaskulären Ereignissen assoziiert war, ohne klare Obergrenze. Die zugrundeliegenden Studien sind Beobachtungsstudien, sodass der Befund zeigt, was mit niedrigerer Sterblichkeit einhergeht, und keine Ursache beweist.

The study · 1

Kodama 2009, JAMA · JAMA

GrimAge and DunedinPACE predict death across groups, a marker not a targetEstablished

In plain terms

Clocks built to track health, such as GrimAge and DunedinPACE, predict who is more likely to die or develop disease across large groups.

In detail

GrimAge, trained on plasma markers and smoking history, predicted time to death and to cardiovascular disease across several cohorts. DunedinPACE, derived from a single birth cohort followed for decades, estimates the pace of aging per year and tracks morbidity and mortality. Both are validated as population predictors; neither has been shown to be a target that changes an individual outcome when the number moves.

The studies · 2

Lu 2019, Aging · Aging (Albany NY)

Belsky 2022, eLife · eLife

Cutting calories slowed one pace-of-aging clock, the age clocks did not, in CALERIEEmerging

In plain terms

In the main human calorie-restriction trial, one pace-of-aging measure slowed slightly while three age clocks did not move on the same blood samples.

In detail

The CALERIE randomized trial applied a methylation panel to participants who cut intake for two years. DunedinPACE, the rate measure, slowed modestly, while the Horvath, Hannum and PhenoAge clocks showed no clear change. The measures disagreeing on the same samples shows how fragile a single clock reading is.

The study · 1

Waziry 2023, Nature Aging · Nat Aging

How it works

Methylation clocks estimate age to within about 3.6 yearsEstablished

In plain terms

An epigenetic clock reads chemical tags on DNA and estimates a person's calendar age to within a few years across most tissues.

In detail

The 2013 method fitted DNA methylation at 353 sites to chronological age across many human tissues, estimating age with a median error near 3.6 years. This is a statistical model of calendar age, and the gap between the estimate and true age is what a biological-age reading reports.

The study · 1

Horvath 2013, Genome Biology · Genome Biol

Aging mapped as twelve interacting hallmarks, a framework not a causeEstablished

In plain terms

Researchers organize aging into a short list of shared cellular changes called the hallmarks, twelve in the current version.

In detail

The 2013 review named nine hallmarks and the 2023 update expanded the set to twelve: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation and dysbiosis. The framework organizes evidence, and because the hallmarks interact and reinforce each other, no one of them can be named the single root cause.

Who this may not transfer to:A framework for organizing evidence, not a measurement taken in people.

The studies · 2

Lopez-Otin 2013, Cell · Cell

Lopez-Otin 2023, Cell · Cell

Eine senolytische Pilotstudie senkte Marker seneszenter Zellen bei neun Menschen, keine GesundheitsergebnisseEmerging

In plain terms

Eine frühe menschliche Pilotstudie fand, dass eine senolytische Arzneimittelkombination Marker seneszenter Zellen senkte, ein Surrogat, kein Gesundheitsergebnis.

In detail

In einer kleinen offenen Pilotstudie reduzierte ein kurzer Kurs Dasatinib plus Quercetin mehrere Marker der seneszenten Zelllast in Blut und Gewebe. Die Studie hatte neun Teilnehmer und keine Kontrollgruppe, und sie maß zelluläre Marker, nicht Krankheits- oder Lebensdauerergebnisse.

Who this may not transfer to:The trial did not report or analyze results by sex, so how far the finding differs between women and men is not established here.

The study · 1

Hickson 2019, EBioMedicine · EBioMedicine

Cholesterol And Lipids

A 12% calorie cut improved cholesterol, blood pressure and insulin over 2 yearsModerate

In plain terms

Healthy adults who cut calories for two years improved cholesterol, blood pressure and insulin sensitivity, all risk markers, not measured lifespan.

In detail

CALERIE randomized 218 healthy non-obese adults to a 25% intake cut or usual diet. They achieved about 12% in practice and improved LDL cholesterol, blood pressure, C-reactive protein and insulin sensitivity over two years. The trial measured risk markers, not survival.

The study · 1

Kraus 2019, Lancet Diabetes Endocrinol · Lancet Diabetes Endocrinol

Evidence And Methods

Clocks read about 1.5 years younger in nine men, with no control groupEmerging

In plain terms

The most cited age-reversal result comes from nine men with no control group, so it reads as a hypothesis, not a demonstration.

In detail

In a one-year open-label study of nine men taking growth hormone with two other drugs, four epigenetic clocks read about 1.5 years younger on average by the end. With no control group and nine participants, the design cannot separate a true change from ordinary variation or regression to the mean.

Who this may not transfer to:Measured only in men aged 51 to 65; whether it applies to women or other ages is untested.

The study · 1

Fahy 2019, Aging Cell · Aging Cell

Go Deeper

• Mitochondria and energy and autophagy, two of the hallmarks you can influence, and hormesis, the controlled-stress principle underneath much of what helps.
• Muscle as an organ, because holding onto muscle and strength is one of the clearest markers of aging well, built by resistance training and fed by protein and muscle.
• Zone 2 training and VO2 max training build the cardiorespiratory fitness with the steepest link to living longer. Walking is the low-friction version most people will actually do.

Common Questions

What do consumer epigenetic aging tests measure?

They are real science and forecast risk across whole populations. But two clocks can read the same blood sample differently, and any single reading is noisy. The aging-reversal claims printed on the boxes have not been shown in people.

If most of it is early, what actually works?

The ordinary habits, and they are not minor. The five everyday habits, plus cardiorespiratory fitness and holding onto muscle, add up to roughly a decade of extra life expectancy in large studies. They act on the very processes the drugs are chasing.