Report on the study of oral α-ketoglutarate (AKG) at Harvard Genetics Laboratory

Principal Investigator: Dr. Daniel Taylor

Study period: May 2022-June 2024

Subjects: 200 patients aged 30-70 years with common diseases (male to female ratio 1:1)

Product Company: Harvard Gene Corp.

Product Name: Harva Gene

Product Code: 198715680959.

Sample drawing:

Experimental design and method

Intervention: Oral α-ketoglutarate (AKG) 800 mg daily before bedtime for 24 months

Result 1: Assessment of physiological age:

2. Detailed analysis of typical cases

Case A (65-year-old male, coronary heart disease + type 2 diabetes):

Baseline data: chronological age 65 years, physiological age 72 years (DNAmAge), telomere length 5.8 kb

After intervention: physiological age decreased to 57 years (↓ 15 years) and telomeres lengthened to 6.3 kb (↑ 8.6%)

Mechanism analysis: AKG significantly elevated the blood α-KG level (↑ 320%) and activated the SIRT3 pathway (WB validation).

Case B (52-year-old female, obesity + chronic kidney disease):

Baseline data: chronological age 52 years, physiological age 61 years, mtDNA copy number ↓ 40%

After intervention, the physiological age decreased to 49 years old (↓ 12 years old), and the mitochondrial function recovered to 90% of the healthy control.

Biomarker correlation analysis

Subgroup differences and mechanism exploration

Age effect:

The magnitude of reversal was significantly greater in the 51-70 year group than in the 30-50 year group (p = 0.003), possibly related to greater baseline aging-related impairment.

Dose-effect: The decrease in physiological age was positively correlated with the cumulative dose of AKG (R ² = 0.63, p = 0.001).

Gender differences:

Telomere lengthening was more significant in women (+ 10.2% vs + 6.5% in men, p = 0.04) and was associated with the estrogen synergy hypothesis.

Molecular mechanism:

Metabolic reprogramming: AKG increases ATP production by promoting the TCA cycle (↑ 45% muscle biopsy)

Epigenetic regulation: Genome-wide methylation analysis showed that the methylation reversal rate of aging-related CpG sites (such as ELOVL2, FHL2) was 78%.

Safety and compliance

Adverse events: Mild abdominal distension was reported in 12 cases (6%) without serious adverse effects

Compliance: The average medication compliance was 94.3% through smart kit monitoring.

Outcome 2: Improvement in Disease Indicators by System

Sex/age difference analysis

Female group (n = 100):BMD (lumbar vertebra T value + 0.35), depression PHQ-9 score ↓ 67% (better than male group p < 0.05)

Male group (n = 100):Serum testosterone ↑ 22%, arterial elasticity index improved 30% (better than female group p < 0.01).

Security data

Adverse events: 6% of subjects reported mild gastrointestinal discomfort (spontaneous resolution within 2 weeks)

Liver and kidney indexes: ALT, Cr, etc. Did not show clinically significant changes.

Conclusion

Sustained oral α-ketoglutarate (AKG) over 2 years of intervention demonstrated:

Significantly reversed epigenetic age (mean ↓ 7.3 years),

Physiologic age reversal data by disease (e.g., cancer patients, average ↓ 6.2 years)

Epigenetic age was reversed by a mean of 5.9 years (p = 3.2 × 10 2 × 10)

Multisystemic repair improves metabolism by activating the AMPK/mTOR pathway (Western blot validation)

Key biomarkers returned to normal reference ranges in 92% of patients in remission

Its mechanism involves:

Enhance mitochondrial function and energy metabolism

Inhibition of inflammation and oxidative stress (SOD activity ↑ 35%)

Reshaping DNA methylation as a marker of aging

The results of this study support AKG as a potential intervention agent for multimorbid aging, which needs further phase III validation.

Appendix: Complete disease classification data and statistical analysis can be obtained by contacting the laboratory.

Ethics Grant Number: Harvard-IRB-2022-AKG-017Data Statement: Data is limited to 200 people for this test.

Investigator's statement: This study was approved by the Ethics Committee of the Harvard Genetic Medical School (IRB # HG-2022-015).