Emerging Research

Brief, non-permanent exposure to the four Yamanaka transcription factors resets markers of cellular age without converting the cell into a stem cell. In progeroid and aged mice, cyclic induction improved tissue markers and extended lifespan (PMID 27984723, Cell 2016, mice). A separate group restored vision in aged mice and in a glaucoma model by resetting the epigenetic state of retinal ganglion cells (PMID 33268865, Nature 2020, mice). Longer-duration partial reprogramming during normal aging has since been characterized (PMID 37118377, Nature Aging 2022, mice).

The constraint is that full reprogramming produces teratomas, so every approach depends on stopping the process partway. There is no published human efficacy trial. EBL tracks this separately on its Evidence Target page, which sets out what published result would move it off Grade D.

Rather than a drug that kills senescent cells for a few days, T cells are engineered to recognize a surface protein carried by senescent cells and clear them on an ongoing basis. In mice, a single dose given at a young age improved metabolic measures much later in life, and the effect persisted (PMID 38267706, Nature Aging 2024, mice).

This is the same class of therapy used in oncology, where it carries known and serious toxicities. No human trial in an aging indication has been published. EBL's graded senolytic A compound intended to clear senescent cells: older cells that have stopped dividing but remain in tissue. entries (the small-molecule compounds) are a separate object with separate evidence and should not be read as support for this.

An alternative to engineered cells: immunise the animal against a peptide expressed by senescent cells and let its own immune system do the clearing. Reported in mice to improve age-related phenotypes and extend lifespan in a progeroid model (PMID 37117524, Nature Aging 2021, mice).

No human trial has been published. The open question is specificity, since the target proteins are not unique to senescent cells.

NAD+ Nicotinamide adenine dinucleotide, a molecule cells use in energy metabolism. Its level falls with age in some tissues. falls with age. One reason is CD38, an enzyme that consumes NAD+ and becomes more abundant in older tissue (PMID 27304511, Cell Metabolism 2016, mice). Blocking the enzyme, rather than supplying more precursor, raised tissue NAD+ and improved metabolic measures in aged mice (PMID 29719225, Cell Metabolism 2018, mice).

This is a claim about a different mechanism, not a stronger version of the NAD precursor evidence. No CD38 inhibitor has published human efficacy data in an aging indication. EBL's grades for NMN, NR and direct NAD+ rest on their own human trials and are unaffected by this work.

Included here for the opposite reason to the entries above: this is the most heavily marketed item in the list and the one with the least behind it. The proposal is that small vesicles released by stem cells carry the signalling cargo responsible for tissue repair, and can be given on their own.

A search of PubMed in July 2026 returned no published randomized human trial of exosome or extracellular-vesicle therapy for an aging or rejuvenation indication. Preparations are nonetheless sold and administered in clinics. EBL states this as an absence of evidence, which is a different finding from evidence of no effect, and a different finding again from the product being ready to use.

The 2023 report that drew the attention found taurine declines with age across species, and that supplementing middle-aged mice extended median lifespan and improved healthspan measures; the human component was 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. (PMID 37289866, Science 2023, mice plus human observational).

The lifespan result is in mice. The human data is correlational, and low taurine may be a marker of ill health rather than a cause of it. That gap is why the graded entry sits at D. See the taurine entry.

The strongest human evidence on this list. A randomized trial in older adults reported improvements in muscle endurance and mitochondrial gene expression (PMID 35050355, JAMA Network Open 2022, randomized human trial). A second randomized trial in middle-aged adults reported improvements in muscle strength and mitochondrial biomarkers A measurable sign in the body, such as a blood test value, used to track a condition or the effect of a treatment. (PMID 35584623, Cell Reports Medicine 2022, randomized human trial).

Two randomized trials with consistent direction is real, and it is also the reason the entry is at C rather than higher: the trials are small, several endpoints The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score. are surrogates, and the sponsor is common to both. See the urolithin A entry.

The widely repeated claim is an average reduction of about eight years in biological age. The source is a 2021 paper in Aging (PMID 34847066, Aging (Albany NY) 2021). It is worth knowing what that paper is before repeating the number.

It is not a randomized controlled trial People are assigned to the treatment or a comparison by chance, so the groups differ only in what they received. It is the design that can show cause and effect.. It is an analysis of methylation-clock results from users of a specific branded formulation, with no randomization, no placebo An inactive substitute made to look like the real treatment, so participants cannot tell which one they received. group and no blinding, and the endpoint is a methylation clock rather than a clinical outcome. Under EBL's grading rule a result attached to a branded formulation also cannot transfer to the ingredient. That is why the entry is at D despite the size of the headline number. See the calcium AKG entry.