An open research framework exploring the biology of aging and the candidate interventions that may slow, interrupt, or reverse biological aging processes.
Authored and maintained by Alyssa Solen | Solen Systems
License: CC BY 4.0
Biological aging is not a single mechanism. It is a compounding cascade of interacting failures across genomic, epigenetic, cellular, metabolic, immune, and systemic levels.
Current medicine is strongest at treating downstream disease. This research framework is focused on upstream aging mechanisms and the question of what may credibly slow, interrupt, or reverse biological aging processes.
The recognized hallmarks of aging include:
- 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
- Dysbiosis
These do not act in isolation. They reinforce each other, which is one reason aging appears to accelerate rather than move at a fixed rate.
- What drives aging most strongly: damage accumulation, epigenetic information loss, programmed decline, or some interacting combination?
- Which candidate interventions show credible evidence of acting on specific hallmarks, and at what level of human evidence?
- Is a unified intervention framework possible, or does each hallmark require targeted approaches?
- What would a minimum viable longevity framework look like for an adult prioritizing cognition, physical capacity, and long healthspan?
This repository does not claim to have final answers. It documents the research process, candidate hypotheses, source review, and evolving synthesis as the science develops.
This repository separates:
- established framework
- early human evidence
- strong animal evidence
- mechanistic speculation
- hype
These are research directions, not treatment recommendations.
No clinical claims.
No anti-aging marketing.
No personal protocol claims presented as science.
No “reversal” language treated as settled unless supported by direct evidence.
If the science moves, the repo moves with it.
Core claim: Aging may reflect loss of cellular information, not only accumulated damage. The underlying DNA sequence remains largely intact, but the regulatory instructions that tell cells how to function degrade over time.
Implication: If the information is still present but poorly expressed, some aspects of aging may be reversible rather than only slowable.
Research direction: Partial expression of reprogramming factors, especially OSK-based approaches, has shown reversal of aging markers in animal retinal tissue and early systemic effects in preclinical models. Full OSKM is generally treated with greater caution because of oncogenic risk.
Evidence maturity: Preclinical. Human translation remains early.
Assessment: Highest structural importance if the findings hold. High upside. High caution.
Core claim: Senescent cells accumulate with age, resist apoptosis, and secrete inflammatory signals that damage surrounding tissue and worsen systemic aging.
Intervention direction: Targeted clearance of senescent cells through senolytic compounds such as dasatinib, quercetin, fisetin, and navitoclax.
Evidence maturity: Strong animal rationale. Early human studies and trials are underway.
Assessment: Medium-high priority. Likely relevant in a multi-modal framework. Human efficacy remains under study.
Core claim: Chronic growth signaling shifts cells away from repair and maintenance. mTOR inhibition may rebalance this by increasing autophagy, repair-state behavior, and damage clearance.
Intervention directions:
- Rapamycin and related mTOR modulation strategies
- Caloric restriction
- Fasting and time-restricted eating approaches
Evidence maturity: Strong mechanistic and animal evidence. Human metabolic and biomarker data exists. Human anti-aging outcome data is still developing.
Assessment: Medium-high priority. One of the strongest mechanistic tracks. Human protocols require caution and should not be oversimplified.
Core claim: NAD+ declines with age and is involved in mitochondrial function, DNA repair, and sirtuin-linked pathways that are relevant to cellular maintenance.
Intervention direction: NAD+ precursor supplementation, primarily NMN and NR.
Evidence maturity: Strong animal data. Human studies show NAD+ levels can be increased, but anti-aging outcomes remain mixed and inconclusive.
Assessment: Medium priority. Biologically relevant. Human outcome evidence is not strong enough for major claims.
Core claim: Telomere shortening contributes to replicative senescence and cellular aging. Preserving telomere function may matter, but direct intervention is complicated.
Intervention directions:
- Lifestyle factors associated with slower attrition
- Experimental telomerase-related approaches
Important caveat: Telomerase biology is tightly linked to cancer biology. Direct telomerase activation without oncogenic risk remains an unsolved problem.
Evidence maturity: Mechanistically important. Direct intervention in humans remains experimental and high caution.
Assessment: Medium priority mechanistically. Not a near-term casual intervention track.
Core claim: Blood-borne factors may influence tissue aging and rejuvenation. Early parabiosis work suggested that systemic environment matters.
Intervention directions:
- Plasma exchange
- Plasma dilution
- Identification of pro-aging and pro-youth circulating factors
Evidence maturity: Scientifically interesting. Human translation remains uncertain. Specific factors and mechanisms remain contested.
Assessment: Low-medium priority. Worth tracking, but not ready for strong practical claims.
- Is there a single dominant upstream driver of aging, or is aging best understood as a network of interacting hallmarks?
- Can epigenetic age clocks such as Horvath, GrimAge, and DunedinPACE serve as reliable intervention-tracking biomarkers?
- Do cognitive longevity and physical longevity share the same primary mechanisms?
- Which combinations of interventions appear additive, synergistic, or counterproductive?
- Where does attempted reversal begin to create unacceptable risk?
- What is the risk-benefit profile of combining senolytics with mTOR modulation?
- Cryonics
- Digital mind upload or substrate transfer
- Germline genetic modification
- Pharmaceutical development
- Clinical recommendations
- Consumer longevity hype
This is an open research framework.
Corrections, source additions, criticism, and evidence-based challenges are welcome.
The goal is accuracy and usefulness, not confirmation of any one theory.
EVIDENCE-BASED contributions only. Speculation should be labeled as such.
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Active. Evolving. No settled conclusions.
Authored and maintained by Alyssa Solen | Solen Systems
CC BY 4.0 | Reuse with attribution