• SRN-901 successfully prolongs the remaining lifespan of middle-aged mice by 34%.  
  • Treating mice with SRN-901 significantly improves several healthspan parameters and metabolic markers.
  • Compared to untreated mice, those treated with SRN-901 exhibit a genetic profile closely resembling that of young mice, with increased levels of multiple pro-longevity genes and decreased levels of several anti-longevity genes. 

Last year, Seragon Biosciences announced the launch of RESTORIN, an advanced aging intervention nutraceutical, developed with patented technologies from Harvard University, Mayo Clinic, and Scripps Research. Now, the research-based biopharmaceutical company has just announced that their aging intervention drug candidate SRN-901, which shares several technologies with RESTORIN, has completed its first pre-clinical assessment. 

One of The Largest Preclinical Studies to Date 

On May 7, 2024, Seragon shed light on several key components of the completed preclinical study, primarily focusing on its efficacy in extending lifespan and improving health markers in mice. Beginning in 2021 and concluding in 2024, this study is one of the most comprehensive aging intervention analyses to date, covering the entire lifespan of over 300 mice. 

Seragon utilized cutting-edge bioinformatic tools like RNA sequencing and machine learning to provide an in-depth analysis of SRN-901’s impact on transcriptomic, metabolomic, and proteomic markers. What’s more, they measured a series of physiological functions and healthspan parameters to further determine SRN-901’s role in enhancing overall health. 

A Dramatic Increase in Lifespan and Healthspan

Prolonging lifespan refers to increasing the total number of years lived, while improving healthspan is about enhancing the quality of those additional years, ensuring they are lived in good health. This is accomplished by delaying or reducing the effects of age-related ailments like physical decline that may alter the aging process, potentially leading to a more sustained and active lifestyle in later years. 

In a detailed interview, David Brown, Ph.D., a senior scientist at Seragon, provided captivating details on the preclinical study’s findings. According to Dr. Brown, treatment in mice with SRN-901 began in middle age, roughly equivalent to someone in their 50’s. Remarkably, SRN-901 demonstrated a ⅓ increase in the remaining lifespan of middle-aged mice, highlighting that SRN-901 has significant potential as a therapeutic intervention for aging and longevity.

SRN-901 Increases Mouse Lifespan. Compared to untreated mice (grey), mice treated with SRN-901 (red) live 34.4% longer. 

Importantly, SRN-901 achieved notable extensions in healthspan among the treated mouse population.

“In what we believe to be one of the most comprehensive systematic assessments of observable age-associated phenotypes, in terms of breadth, we found SRN-901 to improve several key indicators of healthspan,” said Dr. Brown. 

Prior to treatment, aged mice exhibited less than 20% of the endurance displayed by young mice on the treadmill endurance test. However, mice treated with SRN-901 retained over 50% of the endurance level of young mice, suggesting that SRN-901 significantly preserves physical function and mitigates age-related declines in muscle. Additionally, the treated mice had significantly lower frailty scores, indicating better physical health.

The preclinical study with SRN-901 yielded remarkable results, surpassing rapamycin—a drug known for significantly extending rodent lifespan—in achieving greater lifespan extension. The findings suggest that, compared to control mice, the treated mice not only lived longer but also maintained their physical health for longer as they aged. 

Significant Effects at the Molecular Level

To elucidate SRN-901’s effects on genes linked to aging, scientists at Seragon conducted whole-genome transcriptome sequencing, a method that examines an organism’s complete mRNA profile to assess gene activity. 

When asked about SRN-901’s effects on longevity-associated genes, Dr. Brown said, 

“In analyzing longevity-associated gene expression levels, we found that aged mice treated with SRN-901 exhibited expression levels strikingly similar to that of young mice. Interestingly, when compared to the popular NAD+ precursor NMN, SRN-901 had significantly more robust effects.” 

Gene heat maps showing red blocks for increases in genes and blue for decreases in genes. The left and right panel look more alike than the middle one.
SRN-901 (right) outperforms NMN (middle) at restoring longevity-associated gene expression levels to those of young mice (left). 

Dr. Brown also noted that the activity of several well-established pro-longevity genes (Sirt6, Parp1, and Sod2) increased by over 70% on average after treatment. Conversely, the expression of known anti-longevity genes (Igf1r, Ccl4, and IL6) decreased by over 40% on average. Upon analysis of specific pro-longevity pathways, Dr. Brown pointed out that SRN-901 increased the activation of pathways involved in DNA repair, signal transduction, immune function, and programmed cell death.

Furthermore, analysis of metabolic markers revealed that SRN-901 significantly increased gamma-glutamyl glutamine and glutathione, our body’s most abundant and potent antioxidant. Moreover, the study’s investigators observed a substantial decrease in metabolic markers associated with poorer health like blood glucose and uric acid levels.   

A Grand Global Collaboration 

Seragon allocated a substantial amount of resources to complete SRN-901’s three-year study, ensuring the highest standards across the board. 

“An extensive international network of world-class academic institutions and industry leaders collaborated with Seragon to complete this large-scale, broad but in-depth study. The project involved over ten research groups in five major academic institutions, three leading CROs [contract research organizations], and over twenty technology partners,” said Dr. Brown. 

These collaborative efforts allowed Seragon to develop one of the most advanced aging drug candidates to date, providing mTOR inhibition, autophagy and mitophagy activation, NAD+ enhancement, and senolytic stimulation. Optimizing longevity through these multifaceted mechanisms solidifies SRN-901 as a promising and comprehensive therapeutic for combating aging. 

What’s Next? 

The Seragon research team, based in Irvine, California, is optimistic about the initial outcomes of their study. Given the encouraging preliminary results, Seragon is confident in progressing to the next phase. In the coming months, Seragon will publish detailed results once the supplementary analysis is complete. Collectively, SRN-901’s development represents a huge step forward in Seragon’s efforts to redefine the aging intervention market.