Reversing the hallmarks of aging in human tissue.
Rejuvenation Bio develops therapeutics that act on the root mechanisms of aging, from epigenetic drift and telomere loss to cellular senescence and mitochondrial decline. We count a program as working only when aged tissue regains measurable function.
Aging is a biological process that can be studied and measured.
Research over recent decades has shown that the rate of aging differs between species, between individuals and even between tissues of the same body. That variation means aging has mechanisms, and mechanisms can be studied.
Shared root
Cardiovascular disease, cancer, neurodegeneration and many other chronic conditions all rise steeply with age.
Measurable change
Molecular measures of biological age now allow the effect of an intervention to be quantified.
Reversible features
Experimental studies have shown that some features of aged cells and tissues can be returned toward a younger state.
Large unmet need
The global population over 65 is growing quickly, and with it the burden of age-related disease.
Aging is the largest risk factor for chronic disease.
We aim to treat the biological processes of aging directly, so that tissues regain the function they had earlier in life.
Most medicines act on one disease after it appears. Age-related decline, however, underlies many diseases at once. A therapy that restores youthful function could therefore prevent or reverse several conditions together.
We pursue this aim through disciplined research. Each hypothesis must be measurable, each result must be reproducible, and each candidate must earn its way forward on the strength of its data.
Twelve hallmarks of aging, each with a measurable readout.
We organize our research around the hallmarks of aging described by López-Otín and colleagues. For every target we name the measurement that would show it has moved, before any experiment begins.
Primary hallmarks
Sources of molecular damage
- 01
Genomic instability
DNA lesions and somatic mutations accumulate faster than repair can clear them.
γH2AX foci per nucleus · somatic mutation burden - 02
Telomere attrition
Chromosome ends shorten with each division until cells stop dividing or lose control of nearby genes.
Telomere length in kb (TRF) · T/S ratio (qPCR) - 03
Epigenetic alterations
DNA methylation and chromatin marks drift away from their youthful pattern, so cells lose their identity.
DNA methylation age in years · H3K9me3 · H4K16ac - 04
Loss of proteostasis
Misfolded and aggregated proteins build up as chaperone and proteasome capacity fall.
Proteasome activity · aggregate load · HSP70 - 05
Disabled macroautophagy
Cells lose the ability to recycle damaged organelles and protein.
LC3-II flux · p62/SQSTM1 accumulation
Antagonistic hallmarks
Responses that protect at first and harm when chronic
- 06
Deregulated nutrient sensing
Growth signaling through mTOR and IGF-1 stays high while AMPK and sirtuin activity fall.
mTORC1 activity (pS6) · AMPK · IGF-1 - 07
Mitochondrial dysfunction
Respiration weakens, membrane potential drops and mitochondrial DNA is lost.
Oxygen consumption rate (pmol/min) · mtDNA copy number - 08
Cellular senescence
Damaged cells stop dividing but stay alive, and they release factors that inflame surrounding tissue.
SA-β-gal⁺ fraction · p16INK4a and p21 · SASP
Integrative hallmarks
Consequences at the level of tissues and the whole body
- 09
Stem cell exhaustion
Stem cell pools shrink and lose their capacity to regenerate tissue.
Clonogenic capacity · lineage output · repair after injury - 10
Altered intercellular communication
Signals carried in blood and between neighboring cells shift toward an aged profile.
Plasma proteome age · circulating factors - 11
Chronic inflammation
Low-grade inflammation persists without infection or injury.
IL-6 (pg/mL) · hsCRP (mg/L) · TNF-α - 12
Dysbiosis
The gut microbial community loses diversity and stability.
Shannon diversity index · taxon ratios
Reference: López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: an expanding universe. Cell 2023;186(2):243–278.
Programs by target and stage.
| Program | Target | Indication | Discovery | Translation | Preclinical | Phase 1 | Phase 2 |
|---|---|---|---|---|---|---|---|
| RB-101 | Cellular senescence | Pulmonary fibrosis | |||||
| RB-202 | Epigenetic alterations | Age-related muscle loss (sarcopenia) | |||||
| RB-303 | Telomere attrition | Telomere biology disorders | |||||
| RB-404 | Mitochondrial dysfunction | Age-related decline in exercise capacity | |||||
| RB-505 | Chronic inflammation | Age-related chronic inflammation | |||||
| RB-606 | Deregulated nutrient sensing | Age-related metabolic decline (insulin resistance) | |||||
Standards every result must meet.
Defined endpoints
We state hypotheses, primary endpoints and analysis plans before an experiment begins, and we record them so they cannot shift afterward.
Function over markers
A change in a biomarker is not enough. We require evidence that the function of a cell, tissue or organism has improved.
Blinding and randomization
Studies are randomized and, wherever possible, the people who measure outcomes do not know which group received treatment.
Adequate power
Sample sizes are set in advance from expected effect sizes, so that a negative result carries as much weight as a positive one.
Independent replication
Key findings are repeated by separate teams or external laboratories before a program advances.
Safety from the start
Restoring youthful function must not compromise the controls that keep cells stable. We assess safety early and continuously, not only at the regulatory stage.
From biological insight to an approved medicine.
Discovery
Rank hallmark targets by how much each one drives the others, then confirm the link in aged cells.
Translation
Show that moving the target restores function in aged human tissue models, not only the marker.
Preclinical
Establish pharmacology, dose and safety under applicable good laboratory practice.
Clinical
Conduct trials under good clinical practice with independent oversight.
Approval
Seek review by regulatory authorities on the full body of evidence.