A Comprehensive Review of Recent Advances in Anti-Aging Research

Author: FlyingPig2025

1. Introduction

Aging is the single greatest risk factor for the leading causes of death in developed nations, including cardiovascular disease, cancer, neurodegeneration, and metabolic disorders. While the aspiration to extend human healthspan is ancient, the scientific pursuit of interventions that target the biological mechanisms of aging has only recently matured from speculative inquiry into a discipline generating rigorous clinical evidence.

The period from 2023 to 2026 marks a turning point. Several converging forces have reshaped the landscape: the Hevolution Foundation committed over $400 million to healthspan science in just 21 months; Altos Labs launched with$3 billion dedicated to cellular reprogramming; the first long-term randomized controlled trial of rapamycin in healthy humans was completed; and artificial intelligence began generating biological age clocks with predictive power surpassing traditional biomarkers. Simultaneously, unexpected longevity signals from GLP-1 receptor agonists — originally developed for diabetes and obesity — have opened an entirely new pharmacological avenue.

This review provides a comprehensive synthesis of advances across the major domains of anti-aging research. We examine both the scientific findings and the translational challenges, with particular attention to clinical trial evidence, mechanistic insights, and the regulatory and funding environment that shapes which interventions reach human testing.

2. Senolytics and Senescent Cell Clearance

2.1 Mechanistic Basis

Cellular senescence — the irreversible arrest of cell division accompanied by a pro-inflammatory secretory phenotype (SASP) — accumulates with age and contributes to tissue dysfunction across organ systems. Senolytic drugs selectively eliminate these cells, reducing SASP-driven chronic inflammation and potentially restoring tissue function.

2.2 Dasatinib + Quercetin (D+Q)

The dasatinib-quercetin combination remains the most clinically advanced senolytic regimen. A Phase 2 randomized controlled trial for osteoporosis (2024) enrolled 60 postmenopausal women receiving 100 mg dasatinib plus 1,000 mg quercetin for 3 days every 28 days over 20 weeks, demonstrating beneficial effects on bone formation markers, though bone resorption was not significantly reduced. A pilot trial in patients at risk for mild cognitive impairment and Alzheimer's disease (2025) established favorable safety at 100 mg dasatinib plus 1,250 mg quercetin administered for two days every two weeks over 12 weeks.

However, a DNA methylation study published in Aging (2024) introduced complexity: 6 months of D+Q in 19 participants increased epigenetic age acceleration on first-generation clocks, with no significant changes on second- or third-generation clocks. This discordance underscores the need for standardized aging biomarkers in senolytic trials.

2.3 Navitoclax and BCL-Family Inhibitors

Navitoclax (ABT-263), a BCL-2/BCL-xL inhibitor, is among the most potent broad-spectrum senolytics characterized to date. A 2024 nonhuman primate study published in Heliyon demonstrated safety in aged monkeys, with modest reversible thrombocytopenia, reduced senescence and SASP biomarkers in cerebrospinal fluid, and trends toward improvement in neuroinflammation markers. Thrombocytopenia remains the primary barrier to human translation; next-generation approaches include PROTAC-based PZ15227 and the galacto-conjugated prodrug Nav-Gal, which exploit senescence-associated beta-galactosidase activity for targeted delivery.

2.4 Unity Biotechnology and UBX1325

Unity Biotechnology's UBX1325 (foselutoclax), a selective BCL-xL inhibitor, achieved proof of concept in ophthalmology. The Phase 2 BEHOLD study, published in NEJM Evidence (April 2025), demonstrated that a single intravitreal injection provided durable vision improvements in diabetic macular edema. The Phase 2b ASPIRE study (March 2025) showed +5.5 letter vision gains at 36 weeks comparable to aflibercept, but narrowly missed the primary non-inferiority endpoint at weeks 20-24. Despite clinically meaningful results, Unity's board approved dissolution in September 2025 — a cautionary outcome illustrating the gap between biological promise and commercial viability in the senolytic space.

3. Epigenetic Reprogramming

3.1 Partial Reprogramming with Yamanaka Factors

The discovery that transient expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) can reverse cellular age without inducing full dedifferentiation has generated intense research interest. The landmark 2024 study from Rejuvenate Bio, published in Cellular Reprogramming, demonstrated that systemic AAV-delivered inducible OSK (excluding the oncogene c-Myc) in 124-week-old mice extended median remaining lifespan by 109% and significantly improved frailty scores. This represents one of the most dramatic lifespan extensions reported for any single intervention.

3.2 Industry Landscape

The reprogramming space has attracted extraordinary capital:

• Altos Labs ($3 billion, backed by Jeff Bezos and Yuri Milner) continues preclinical work with Shinya Yamanaka as scientific advisor
• Retro Biosciences (funded by Sam Altman, reportedly raising $1 billion) collaborated with OpenAI to create GPT-4b micro, a specialized protein-engineering model that redesigned Yamanaka factor variants achieving over 50-fold higher expression of reprogramming markers than wild-type factors
• Turn Biotechnologies acquired ARMMs vesicular delivery technology (March 2025) and plans clinical trials for skin rejuvenation in 2026
• Life Biosciences (founded by David Sinclair) is entering human trials in Q1 2026 for optic neuropathies with its ER-100 partial epigenetic reprogramming therapy
• Shift Bioscience identified SB000, described as the first single-gene intervention to rejuvenate cells from multiple germ layers with efficacy rivaling full Yamanaka factor cocktails while avoiding dangerous pluripotency pathways

3.3 Safety Considerations

Full OSKM expression induces teratoma formation, and partial reprogramming cannot correct accumulated DNA mutations. The field is approaching a critical inflection point: multiple first-in-human trials are expected in 2026, and the safety profiles observed in these trials will likely determine the trajectory of reprogramming-based therapies for the next decade.

4. NAD+ Metabolism and Sirtuins

4.1 Precursor Comparison

A head-to-head comparison published in Nature Metabolism (2025) by Christen et al. directly compared NMN, NR, and nicotinamide in humans. Both NMN and NR approximately doubled circulating NAD+ levels after 14 days, while nicotinamide achieved this only transiently at 4 hours. The study revealed that gut bacteria convert both NMN and NR to nicotinic acid and that both precursors modulate the microbiome to increase short-chain fatty acid production.

4.2 NMN Clinical Evidence

A meta-analysis of 9 studies encompassing 412 participants found NMN significantly improved gait speed and muscle function. A dose-response study (80 participants; 300, 600, and 900 mg doses) demonstrated dose-dependent NAD+ increases, improved walking distance, and stable biological age versus increased biological age in the placebo group. Sex-specific effects have emerged: NMN improved insulin sensitivity specifically in postmenopausal women. A February 2025 trial demonstrated that liposomal NMN formulations significantly increased NAD+ compared to non-liposomal forms, suggesting bioavailability improvements may enhance clinical outcomes.

4.3 Novel Sirtuin Activators

Guan and colleagues (2025) engineered molecules that nearly double sirtuin 3 (SIRT3) activity even at half-normal mitochondrial NAD+ concentrations. These direct activators are described as more effective than NAD+ precursors for mitochondrial rejuvenation, with clinical trials planned. This approach circumvents the bottleneck of NAD+ delivery to mitochondria.

4.4 Limitations

A meta-analysis found NMN modestly improves triglycerides in overweight and obese participants, but most clinically relevant body composition outcomes were not significantly affected. Critically, none of the published studies measured sirtuin activity levels directly, leaving the mechanistic link between NAD+ supplementation and sirtuin-mediated benefits incompletely validated in humans.

5. Rapamycin and mTOR Inhibition

5.1 The PEARL Trial

The Participatory Evaluation of Aging with Rapamycin for Longevity (PEARL) trial represents a milestone as the first long-term randomized controlled trial of rapamycin in healthy humans. Led by Sajid Zalzala and crowdfunded through Lifespan.io, the trial enrolled 114 healthy individuals aged 50-85 who received 5 mg or 10 mg rapamycin or placebo weekly for 48 weeks. Key findings include: no severe adverse effects; the 10 mg dose prevented muscle loss in women and bone loss in men; and gastrointestinal issues were the most common side effect. The trial's reliance on self-reporting and lack of direct lifespan endpoints limit interpretation, but the safety profile supports further investigation.

5.2 Organ-Specific Pilots

A 2025 cardiovascular pilot demonstrated that 1 mg rapamycin daily in healthy older men was safe and showed potential for ameliorating age-related cardiovascular dysfunction. An open-label Phase 1 Alzheimer's pilot (Gonzales et al., 2025) found that rapamycin was not detected in cerebrospinal fluid but nonetheless produced measurable changes in neurodegenerative disease and inflammatory biomarkers. An Oxford immunology study showed rapamycin prevented DNA damage in T cells and increased survival of stressed T cells by 3-fold.

5.3 The Dog Aging Project (TRIAD)

The Test of Rapamycin in Aging Dogs (TRIAD) is the most ambitious real-world lifespan trial of a pharmacological intervention. This parallel-group, double-masked, randomized, placebo-controlled, multicenter trial enrolls middle-aged dogs (7+ years, 44+ lbs). In January 2025, the Dog Aging Project received a $7 million NIH grant to expand from 170 dogs across 20 sites to 580 dogs, with each animal participating for 3 years plus 2 additional years of monitoring. Earlier studies showed rapamycin improved both diastolic and systolic cardiac function in dogs with no clinical side effects.

6. GLP-1 Receptor Agonists: An Unexpected Longevity Candidate

6.1 Epigenetic Age Reduction

Perhaps the most surprising development in recent anti-aging research involves GLP-1 receptor agonists, originally developed for type 2 diabetes and obesity. A 2025 randomized trial in people with HIV-associated lipohypertrophy demonstrated that semaglutide reduced epigenetic age by 3-5 years across multiple organ-specific clocks. Adjusted differences favoring semaglutide were striking: blood (-4.37 years), brain (-4.99 years), inflammation (-5.01 years), heart (-4.34 years), kidney (-4.20 years), liver (-4.19 years), and metabolic measures (-4.72 years). This constitutes the first RCT evidence that a GLP-1 agonist modulates epigenetic aging biomarkers.

6.2 Multi-Organ Benefits

The SELECT trial (over 17,000 adults across 41 countries) demonstrated cardiovascular benefits in patients without diabetes. The FLOW trial showed renal protective effects, slowing chronic kidney disease progression. Semaglutide reduces CRP, IL-6, and TNF-alpha independently of weight loss, and at the vascular level reduces leukocyte adhesion and lowers ICAM-1 and VCAM-1 expression.

6.3 Neuroprotection

Observational studies in diabetes patients associate semaglutide with 40-70% lower risk of Alzheimer's diagnosis. The Phase 3 EVOKE and EVOKE+ trials are currently evaluating semaglutide in early-stage symptomatic Alzheimer's disease — trials that could establish GLP-1 agonists as the first pharmacological class with demonstrated benefits across cardiovascular, renal, metabolic, and neurodegenerative aging.

6.4 Regulatory Implications

A Nature Biotechnology commentary (2025) noted that GLP-1 agonists have vastly more human safety data than any previous anti-aging candidate. Eli Lilly is reportedly planning a TAME-like study with GLP-1 agonists that could seek an aging indication — a development that could accelerate regulatory acceptance of aging as a treatable condition.

7. Telomere Biology

7.1 TERT Reactivation

A 2024 study from MD Anderson Cancer Center, published in Cell, identified a small molecule compound (TAC) that restores physiological levels of telomerase reverse transcriptase. In aged animal models, TAC maintenance reduced cellular senescence, spurred neurogenesis with improved memory, and enhanced neuromuscular function. Notably, TERT functioned as a transcription factor affecting neurogenesis, learning, and inflammation genes — rejuvenating neurons and cardiac cells without requiring cell division.

7.2 Telo-seq

The Salk Institute developed Telo-seq (2024, Nature Communications), a sequencing tool providing chromosome-arm-specific telomere length measurements with unprecedented resolution. This technology revealed that each chromosome arm has different telomere lengths with significantly different shortening rates across tissues and cell types — a finding that challenges the utility of average telomere length as a biomarker.

7.3 Telomeres vs. Epigenetic Clocks

A 2025 study in Aging Cell found telomere length showed inconsistent associations with mortality across cohorts, while epigenetic clocks (GrimAge, PhenoAge) were more robust and consistent mortality predictors. This suggests the field is moving toward epigenetic clocks as the preferred biological age metric, though telomere biology remains mechanistically important.

8. AI and Machine Learning in Aging Research

8.1 Evolution of Biological Age Clocks

DNA methylation clocks have progressed through four generations:

1. First generation: Chronological age-trained (Horvath 2013, Hannum 2013)
2. Second generation: Phenotype and mortality-informed (PhenoAge, GrimAge, GrimAge2)
3. Third generation: Pace-of-aging measures (DunedinPACE)
4. Fourth generation: Causality-enriched models using Mendelian randomization (CausAge, DamAge, AdaptAge)

DunedinPACE continues to be preferred for intervention studies due to its high test-retest reliability and sensitivity to pre-/post-treatment changes. A major scientific competition drew 37 teams submitting over 550 clocks to predict chronological age, age at death, and healthspan from anonymized data — demonstrating the maturity and competitiveness of this subfield.

8.2 Proteomic and Multi-Modal Clocks

Kuo et al. (2024) developed PAC using 2,923 proteins from 53,021 individuals, achieving a Spearman correlation of 0.77 between chronological and estimated biological age. Multi-omic integration is increasingly standard.

8.3 AI-Driven Drug Discovery

Galkin et al. (2024) introduced Precious3GPT, the first transformer model for drug and biomarker discovery in aging research, developed by Insilico Medicine. ClockBase, integrating over 2 million molecular aging samples, identified age-modifying compounds with a 70% validation rate for lifespan extension in model organisms. TxGNN (Huang et al., 2024) uses graph neural networks for zero-shot drug repurposing across aging-related conditions.

9. Parabiosis and Plasma Factors

9.1 The Plasma Dilution Paradigm

The Conboys' work (2020-2021) fundamentally shifted the parabiosis field by demonstrating that diluting old blood had stronger rejuvenating effects than infusing young blood. This suggests benefits derive primarily from removing pro-aging factors rather than adding pro-youth factors.

9.2 Human Plasmapheresis

A 2025 human trial revealed that plasmapheresis without albumin replacement actually increased epigenetic age acceleration markers, while plasmapheresis with albumin supplementation positively impacted aging biomarkers. This distinction has important implications for therapeutic plasma exchange protocols.

9.3 Specific Factors

Klotho: A single low-dose infusion (10 ug/kg) in geriatric rhesus monkeys showed remarkable cognitive improvements persisting at least two weeks. Klotho Neurosciences is developing gene and protein therapies, with lead project KLTO-202 targeting ALS.

GDF11: Remains controversial. While some research shows it reverses cardiac hypertrophy, other studies failed to replicate cardiac effects and suggest GDF11 may hinder muscle regeneration. Elevian, Inc. is planning a Phase 1 trial for brain revascularization after stroke.

PEDF (Pigment Epithelium-Derived Factor): Identified in 2024 as a systemic mediator of rejuvenation by young blood using an in vitro parabiosis system.

10. Caloric Restriction and Fasting

10.1 CALERIE Trial

The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial continues to yield important findings:

• DunedinPACE analysis: The intervention slowed the pace of biological aging as measured by DNA methylation — direct evidence that caloric restriction slows molecular aging in humans
• Cardiometabolic outcomes: Significant improvements in CRP (p=0.012), insulin sensitivity (p<0.0001), and metabolic syndrome score (p<0.0001)
• Telomere dynamics (2024, Aging Cell): Mixed results — accelerated telomere attrition in Year 1, with different patterns during sustained CR without further weight loss
• Multi-omic resource (2024-2025): Release of multi-omic datasets (genotypes, DNA methylation, mRNA, small RNA) from 218 participants across blood, muscle, and adipose tissue (2,327 total samples)

10.2 Genetics vs. Diet

A landmark 2024 Nature study in 960 genetically diverse female mice showed lifespan extension proportional to dietary restriction, but genetics had a larger influence on lifespan than dietary restriction. This finding has critical implications for translational relevance: individual genetic background may determine who benefits most from CR interventions.

10.3 Intermittent Fasting Mechanisms

A 2024 study in Nature Cell Biology revealed that intermittent fasting increases spermidine levels, which enhances cell resilience through autophagy activation — establishing a mechanistic link between fasting regimens and the proteostasis machinery. The DiAL-Health Study at Pennington Biomedical Research Center is comparing 16:8 time-restricted eating with traditional CR in humans aged 25-49.

11. Mitochondrial Dysfunction and Mitophagy

11.1 Urolithin A Clinical Evidence

Urolithin A (UA), a gut-microbiome-derived metabolite that activates mitophagy, has accumulated the strongest clinical evidence of any mitophagy-enhancing intervention:

• MitoIMMUNE Trial (Nature Aging, 2025): In 50 healthy middle-aged adults, 1,000 mg/day UA for 4 weeks expanded naive-like CD8+ T cells (treatment difference 0.50 percentage points; P=0.0437), increased CD8+ fatty acid oxidation capacity (treatment difference 14.72 percentage points; P=0.0061), augmented mitochondrial biogenesis, and improved TNF secretion by T cells
• ATLAS Trial: 4-month RCT showed approximately 12% improvements in muscle strength, plus reduced CRP and plasma acylcarnitines
• Cardiovascular evidence (iScience, January 2025): UA reduced systolic and diastolic cardiac dysfunction in aging and heart failure models, associated with recovery of mitochondrial ultrastructural defects

11.2 Therapeutic Development

Timeline/Amazentis (marketed as Mitopure) has accumulated over 15 years of research, with registered clinical trials addressing immune health (NCT05735886) and mitochondrial quality (NCT06555706). UA represents a model for translating a naturally occurring metabolite into a standardized therapeutic intervention.

12. Proteostasis and Autophagy

12.1 Spermidine as an Essential Fasting Mediator

A pivotal 2024 study in Nature Cell Biology established spermidine as the essential mediator of fasting-induced autophagy. Spermidine levels increase upon fasting and caloric restriction in yeast, flies, mice, and human volunteers. Critically, blocking endogenous spermidine synthesis abolished fasting-induced autophagy and eliminated the lifespan-extending, healthspan-promoting, cardioprotective, and anti-arthritic effects of fasting.

12.2 Clinical Trials

The POLYCAD trial — a single-center RCT at Aarhus University Hospital — randomized 187 patients aged 65+ with coronary artery disease to 24 mg/day spermidine or placebo. Recruitment began January 2024 and completed August 2025, making it the longest spermidine intervention trial to date. A 2025 cognitive aging study (Pekar et al.) reported that 1-year supplementation with 3.3 mg spermidine improved cognitive performance in 42% of older adult participants.

13. Inflammaging

13.1 Biomarker Landscape

A 2024 systematic review and meta-analysis in Frontiers in Immunology confirmed that elevated IL-6, TNF, and IL-1beta are risk factors across cardiovascular and other age-related diseases, with IL-6 being the most predictive biomarker of all-cause mortality. Soluble TNFR1 (sTNFR1) was proposed in 2024 as having greater reproducibility than IL-6 for assessing chronic inflammation in older adults.

13.2 The Inflammatory Clock of Aging (iAge)

Blood inflammatory mediator profiles can now estimate biological age through the iAge clock, which tracks with multimorbidity, immunosenescence, frailty, and cardiovascular aging. This clock complements DNA methylation-based measures by capturing the inflammatory dimension of aging.

13.3 Mechanistic Links

IL-1beta, IL-6, and TNF induce mitochondrial dysfunction with reduced ATP synthesis-driven respiration and reduction of the NAD+:NADH ratio, establishing a mechanistic link between inflammaging and metabolic decline. This convergence suggests that anti-inflammatory interventions may have downstream benefits on mitochondrial function and NAD+ metabolism.

13.4 Therapeutic Approaches

NF-kappaB pathway inhibitors show experimental efficacy, but clinical translation has been challenging: the TNF inhibitor etanercept delayed aging phenotypes experimentally but failed to show mortality benefits in heart failure trials. The anti-inflammatory effects of GLP-1 agonists and senolytics represent more promising avenues, as they address inflammation through distinct mechanisms (metabolic signaling and senescent cell clearance, respectively).

14. Funding Landscape and Major Organizations

The funding environment for anti-aging research has been transformed:

The Hevolution Foundation's HF-GRO program has committed $115 million over 5 years, with notable awards including$20.2 million to Albert Einstein College of Medicine for senescence research and $32.3 million to Northwestern University for proteostasis studies. NIA, however, reduced FY2024 competing awards by 16% on average and is preparing for tighter budget scenarios.

15. Landmark Clinical Trials: Status and Outlook

15.1 The TAME Trial

The Targeting Aging with Metformin (TAME) trial, designed to randomize 3,000 adults aged 65-79 to metformin (1,500 mg/day) or placebo for 4 years, remains the most symbolically important trial in the field. Led by Nir Barzilai at Albert Einstein College of Medicine, the trial has secured FDA agreement with its design — establishing a regulatory precedent for aging as a treatable condition — but as of early 2026 has still not launched due to persistent funding gaps (estimated cost $45-70 million). ARPA-H is now involved in planning.

Supporting evidence continues to accumulate: a 2024 primate study showed metformin rolled back molecular aging clocks by 4-6 years, and a Women's Health Initiative analysis (2025) found 30% lower risk of death before age 90 with metformin versus sulfonylurea monotherapy (HR 0.70; 95% CI: 0.56-0.88).

15.2 Trial Landscape Summary

16. Discussion and Future Directions

16.1 Convergence of Mechanisms

A striking feature of recent research is the mechanistic convergence across seemingly distinct interventions. Caloric restriction, rapamycin, senolytics, spermidine, and GLP-1 agonists all reduce chronic inflammation. NAD+ precursors, urolithin A, and caloric restriction all improve mitochondrial function. Epigenetic reprogramming, senolytics, and exercise all reduce the burden of senescent cells. This convergence suggests that aging involves a relatively small number of interconnected pathways, and that interventions targeting any node in this network may produce benefits across multiple hallmarks of aging.

16.2 The Measurement Revolution

The development of fourth-generation biological age clocks — incorporating causal inference through Mendelian randomization — addresses a fundamental challenge: distinguishing biomarkers that merely correlate with aging from those that causally drive it. The availability of standardized, sensitive measures like DunedinPACE is accelerating clinical translation by providing endpoints that can detect intervention effects in shorter timeframes than mortality studies require.

16.3 Translational Challenges

Several critical gaps persist:

1. Regulatory vacuum: The FDA does not recognize aging as a disease indication, forcing trials to target specific diseases rather than aging itself. The TAME trial's design acceptance was a first step, but no trial has yet been completed under this framework.
2. Genetic heterogeneity: The 2024 Nature mouse study demonstrating that genetics outweighs dietary restriction in determining lifespan raises questions about universal applicability of anti-aging interventions.
3. Biomarker standardization: The discordant results of D+Q on different generations of epigenetic clocks highlight the need for consensus on which biological age measures should serve as primary endpoints.
4. Commercial sustainability: Unity Biotechnology's dissolution despite positive clinical results illustrates that biological efficacy alone is insufficient without viable commercial models.

16.4 The 2026 Inflection Point

Multiple first-in-human trials for epigenetic reprogramming are expected in 2026 (Life Biosciences ER-100, Turn Biotechnologies skin rejuvenation). The TRIAD dog aging study is expanding to generate the most rigorous mammalian lifespan data for any pharmacological intervention. GLP-1 agonists may enter aging-specific trials. And AI-driven drug discovery platforms are generating candidates at unprecedented speed. The next two to three years will likely determine which of the current approaches — pharmacological, genetic, or combination — will define the first generation of clinically validated anti-aging therapies.

17. Conclusion

Anti-aging research has transitioned from a field dominated by model organism studies and mechanistic speculation to one generating substantial clinical evidence in humans. The period from 2023 to 2026 has produced several landmark results: the first RCT evidence that GLP-1 agonists reduce epigenetic age across multiple organ systems; the completion of the PEARL rapamycin trial establishing long-term safety in healthy adults; the demonstration that partial epigenetic reprogramming can extend lifespan by over 100% in aged mice; and the emergence of AI-driven biological age clocks with causal inference capabilities.

Yet the field remains at an early clinical stage. The TAME trial — conceived as the foundational proof that aging itself can be targeted — has not begun. Regulatory frameworks lag behind scientific progress. And the translation gap between dramatic animal results and modest human outcomes persists across every intervention class.

What has changed is the scale of investment, the sophistication of measurement, and the convergence of evidence across multiple independent approaches. The question is no longer whether biological aging can be modulated, but which interventions, in which combinations, for which individuals, will prove safe, effective, and accessible. The answers are likely to emerge within the current decade.

References

1. Hickson, L.J. et al. "Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial." EBioMedicine 47: 732-746, 2019.
2. Gonzales, M.M. et al. "Senolytic therapy in mild Alzheimer's disease: a Phase 1 feasibility trial." Nature Medicine 29: 2481-2488, 2023.
3. Hickson, L.J. et al. "Phase 2 trial of dasatinib plus quercetin for osteoporosis." 2024.
4. Ocampo, A. et al. "In vivo amelioration of age-associated hallmarks by partial reprogramming." Cell 167(7): 1719-1733, 2016.
5. Macip, C.C. et al. "Gene therapy-mediated partial reprogramming extends lifespan and reverses age-related changes in aged mice." Cellular Reprogramming 26(1): 24-32, 2024.
6. Christen, S. et al. "Head-to-head comparison of NMN, NR, and nicotinamide." Nature Metabolism, 2025.
7. Zalzala, S. et al. "PEARL: A randomized controlled trial of rapamycin in healthy adults." 2025.
8. Semaglutide epigenetic age trial in HIV-associated lipohypertrophy. 2025.
9. Lowe, D. et al. "TERT reactivation by small molecule TAC." Cell, 2024.
10. Kuo, C.L. et al. "Proteomic aging clock from 53,021 individuals." 2024.
11. Galkin, F. et al. "Precious3GPT: Transformer for aging drug discovery." 2024.
12. Conboy, I.M. et al. "Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin." Aging 12(10): 8790-8819, 2020.
13. Spadaro, O. et al. "Caloric restriction in humans reveals immunometabolic regulators of health span." Science 375(6581): 671-677, 2022.
14. "Dietary restriction and lifespan in genetically diverse mice." Nature, 2024.
15. Eisenberg, T. et al. "Spermidine as essential mediator of fasting-induced autophagy." Nature Cell Biology, 2024.
16. Liu, S. et al. "Urolithin A modulates immune aging in the MitoIMMUNE trial." Nature Aging, 2025.
17. Unity Biotechnology. "ASPIRE Phase 2b topline results." Press release, March 2025.
18. Unity Biotechnology. "UBX1325 BEHOLD results." NEJM Evidence, April 2025.
19. Nature Biotechnology. "Could GLP-1 agonists be the first longevity drugs?" 2025.
20. Barzilai, N. "TAME: Targeting Aging with Metformin." AFAR, 2026.
21. Dog Aging Project. "TRIAD expansion." Texas A&M University, January 2025.
22. Hevolution Foundation. "$400M funding commitment." 2024.
23. Frontiers in Immunology. "IL-6, TNF, IL-1beta meta-analysis in age-related disease." 2024.
24. Horvath, S. "DNA methylation age of human tissues and cell types." Genome Biology 14: R115, 2013.
25. Belsky, D.W. et al. "DunedinPACE, a DNA methylation biomarker of the pace of aging." eLife 11: e73420, 2022.