The Hallmarks of Aging

No intervention has been shown in a human randomized trial to reduce genomic damage and thereby extend life or reduce disease. Damage markers can be measured; moving them has not been linked to a hard outcome.

Telomere length is measurable but is a noisy individual-level marker, and no randomized human trial has shown that lengthening telomeres improves survival or disease outcomes. EBL reads it as context, never as a result on its own.

Epigenetic clocks A test that estimates biological age from chemical marks on DNA (DNA methylation). are the basis of most consumer biological-age tests. They are trained to predict age and mortality in populations; they have not been validated as endpoints The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score. that, when moved, deliver a proven clinical benefit to an individual.

Central to Alzheimer's and Parkinson's biology, where it is studied intensively. As a general longevity target in healthy adults there is no randomized human evidence that improving proteostasis changes outcomes.

This is the mechanism most often invoked to sell fasting protocols. Autophagy The process cells use to break down and recycle their own worn-out parts. has not been measured directly in the fasting trials that are cited for it. Those trials measured weight, glucose, and lipids. EBL grades the diets on what was actually measured, which is why caloric restriction, 5:2 intermittent fasting, the ketogenic diet, and the fasting-mimicking diet all sit at C.

The most heavily targeted hallmark in the supplement market, and the source of most mechanistic marketing language. Human trials here overwhelmingly report surrogate endpoints A lab value or measurement used in place of the outcome that matters, such as LDL cholesterol standing in for heart attacks. Moving a surrogate does not always move the outcome. (glucose, insulin, lipids) not survival or disease incidence.

A large fraction of the supplement market is sold on this hallmark. Where human RCTs exist they typically measure exercise capacity, fatigue, or a lab marker over weeks to months. That is what earns a grade on this site, not the mitochondrial rationale.

Senolytics A compound intended to clear senescent cells: older cells that have stopped dividing but remain in tissue. are the most-hyped intervention class in longevity. Human trials so far are small, short, and focused on specific conditions. There is no completed randomized trial showing that clearing senescent cells extends life or prevents age-related disease in people.

Widely used to market clinic-administered stem-cell and exosome procedures. For general age-related decline, the randomized human evidence supporting those procedures does not exist.

Hormone replacement is the most-studied intervention touching this hallmark, and it has substantial randomized evidence. For defined clinical indications, not as a general anti-aging strategy. The distinction matters.

This hallmark has the strongest human outcome data of the twelve. Inflammatory markers such as hs-CRP High-sensitivity C-reactive protein, a blood marker of low-grade inflammation. predict cardiovascular events, and randomized anti-inflammatory drug trials have moved hard endpoints An outcome that matters directly to a person and is counted without judgment, such as death, heart attack, stroke or fracture.. That evidence belongs to specific drugs at specific doses. It does not transfer to supplements marketed as anti-inflammatory.

Almost all of the compelling data is observational Research that watches what people already do rather than assigning a treatment. It can show that two things travel together, not that one causes the other. or from animal models. The randomized human probiotic trials that exist are strain-specific and short, and their results do not generalize across products or species.