InfiniAge™

An important step in the research was leveraging artificial intelligence to find novel metabolite and proteomic associations to biological aging. During this process, Harvard researchers asked which metabolites, clinical values, and proteins were most predictive of longevity. They found a total of 38 individual factors which were predictive of time until death. Furthermore, they were able to find several nutrition-related biomarkers which we used to design the best in class supplement to improve epigenetic aging. Together, we believe that InfiniAge™ is the strongest combination of ingredients to reverse the most predictive, biological age biomarkers to date.

Based on that information, InfiniAge™ was born. It contains a precise blend of 7 key ingredients, including Calcium Alpha-Ketoglutarate, Uridine Monophosphate, Ergothionine, N-Acetyl L-Cysteine, Lutein (Carotene-2,2,-diol) Aronia Melanocarpa Extract, and Zinc. Many of these ingredients have vast publications which describe a multitude of benefits with regard to the aging process. We have also included what could be considered novel ingredients, relative to longevity, into this formulation as well. Each of these has been specifically identified in the OMICm Age algorithm which can beneficially impact OMICm Age factors.

For instance, in the development of OMICm Age, we took into effect that individuals who had higher plasma concentrations of Uridine and Lutein were generally associated to have a better OMICm Age; and as a result, have longer lives with less morbidity. We also included ingredients to change other OMICm Age measured variables, such as zinc and Aronia Melanocarpa Extract. Zinc and Aronia Melanocarpa Extract help to increase PON1.

Serum paraoxonase and arylesterase 1 (PON1) is an enzyme encoded by the PON1 gene. Serum PON1 is secreted mainly by the liver, although local synthesis occurs in several tissues, PON1 protein is found in almost all tissues. PON1 is also a major anti-atherosclerotic component of HDL Cholesterol (good cholesterol). The PON1 gene is activated by PPAR-γ, which increases synthesis and release of paraoxonase 1 enzyme from the liver, reducing atherosclerosis. In the OMICm Age cohort, researchers found that higher levels of PON1 activity were associated with better aging. Some studies have shown that Aronia Melanocarpa Extract can increase PON1 activity levels by over 15%.

Zinc

Zinc, a nutrient found throughout your body, helps your immune system and metabolism function. Zinc is also important to wound healing and your sense of taste and smell. However, like aronia melanocarpa extract, it has also been shown to support PON1 activity levels. In addition to this, the first trial on epigenetic age reversal (the TRIMM Trial), also supplemented with zinc.^1,2,3

N-Acetyl L-Cysteine

N-Acetyl L-Cysteine (NAC), a derivative of the amino acid cysteine, has been of interest in the context of longevity due to its potential impact on various mechanisms associated with aging. NAC is a precursor to glutathione, a key antioxidant in the body, and it plays a crucial role in mitigating oxidative stress and protecting cells from damage. Additionally, NAC has been investigated for its ability to influence cellular processes such as apoptosis and DNA repair. Some studies, particularly in animal models, have suggested that NAC supplementation may have a positive influence on longevity by promoting healthier aging and reducing the risk of age-related diseases. Nevertheless, the exact mechanisms and its application to human longevity warrant further research to establish a clear causal relationship.^4,5 

In the creation of OMICm Age, we see that higher cystine levels are negative for biological aging. This is most likely because cystine is upregulated with oxidative stress.⁶ Supplementations with glutathione precursors might help reduce this oxidative stress burden and improve OMICm Age.

Lutein (Carotene-2,2,-diol)

Carotenoids have long been associated with good vision and anti-inflammatory action. However, there is mounting evidence that carotenoid levels are one of the most highly associated biomarkers to improve epigenetic age algorithms. Not only was this particular metabolite associated with better OMICm Age in the Harvard cohort, it also has been shown to be highly linked to other important 2nd generation algorithms like grimage. Uridine and Lutein were the only 2 metabolites selected with positive effects on OMICm Age acceleration.⁷

Calcium Alpha-Ketoglutarate

Alpha-ketoglutarate, an intermediate in the tricarboxylic acid cycle, has garnered attention in the field of longevity research due to its potential impact on aging. This compound is involved in various metabolic processes, including energy production and amino acid metabolism. Studies in model organisms have suggested that supplementation with alpha-ketoglutarate may support lifespan and modulate cellular processes such as mitochondrial function and mitigating oxidative stress.⁸ Furthermore, it has been shown to influence pathways associated with nutrient sensing and cellular maintenance, such as mTOR signaling. As the exact mechanisms underlying its effects on longevity in humans require further investigation, its translation to practical interventions for extending human lifespan remains an ongoing area of scientific exploration.

Uridine Monophosphate

Uridine is an important building block used in the creation of RNA.While traditionally it has been used to help support brain health, synaptic connections, and cholinergic function; it is also highly linked to longevity and regeneration. For instance, in a cross-species study, metabolomic analysis identifies uridine as a potent regeneration promoting factor across many mammals.9 Other studies have also observed significant association of uridine with risk for all-cause mortality.¹⁰ 

In fact, a separate study of longevity in the Women’s Health Initiative (WHI) found that ratios of isocitrate, uridine and lysine were associated with a 2-3-fold higher odds of attaining longevity. Uridine might also show tissue specific anti-aging effects, such as improving intestinal aging.¹¹

Ergothioneine

While ergothioneine has not directly been studied in relation to epigenetic aging, it has many proposed benefits for aging. Ergothioneine (EGT) is a hydrophilic anti-oxidant compound which has been shown to exert anti-aging properties. In addition to its antioxidant effect, EGT has been reported to have anti-senescence, anti-inflammatory and anti-neurodegenerative properties. It is also a compound which is traditionally limited in american based diets. In animal studies, this metabolite has been able to increase mouse lifespan by up to 40%.^12,13,14

Aronia Melanocarpa Extract

While serum PON1 is secreted mainly by the liver, local synthesis occurs in several tissues and PON1 protein is found in almost all tissues. PON1 is also a major component of HDL Cholesterol (good cholesterol). The PON1 gene is activated by PPAR-γ, which increases synthesis and release of paraoxonase 1 enzyme from the liver, supporting healthy arterial integrity.^15,16

In the OMICm Age cohort, researchers found that higher levels of PON1 activity were associated with better aging. In fact, it was the second most protective protein in the entire algorithm. In a meta-analysis of nutritional ingredients shown to improve PON1 levels and activity, Aronia melanocarpa (chokeberry) extract was the most effective at increasing PON1 activity.¹⁷

1. Fahy GM, Brooke RT, Watson JP, Good Z, Vasanawala SS, Maecker H, Leipold MD, Lin DTS, Kobor MS, Horvath S. Reversal of epigenetic aging and immunosenescent trends in humans. Aging Cell. 2019 Dec;18(6):e13028. doi: 10.1111/acel.13028. Epub 2019 Sep 8. PMID: 31496122; PMCID: PMC6826138.

2. Rahimi-Ardabili B, Argani H, Ghorbanihaghjo A, Rashtchizadeh N, Naghavi-Behzad M, Ghorashi S, Nezami N. Paraoxonase enzyme activity is enhanced by zinc supplementation in hemodialysis patients. Ren Fail. 2012;34(9):1123-8. doi: 10.3109/0886022X.2012.717479. Epub 2012 Sep 6. PMID: 22950600.

3. Lou-Bonafonte JM, Gabás-Rivera C, Navarro MA, Osada J. The Search for Dietary Supplements to Elevate or Activate Circulating Paraoxonases. Int J Mol Sci. 2017 Feb 15;18(2):416. doi: 10.3390/ijms18020416. PMID: 28212288; PMCID: PMC5343950.

4. Brantley MA Jr, Osborn MP, Sanders BJ, Rezaei KA, Lu P, Li C, Milne GL, Cai J, Sternberg P Jr. Plasma biomarkers of oxidative stress and genetic variants in age-related macular degeneration. Am J Ophthalmol. 2012 Mar;153(3):460-467.e1. doi: 10.1016/j.ajo.2011.08.033. Epub 2011 Oct 29. PMID: 22035603; PMCID: PMC3288635.

5. Elshorbagy, A., Bastani, N.E., Lee-Ødegård, S. et al. The association of fasting plasma thiol fractions with body fat compartments, biomarker profile, and adipose tissue gene expression. Amino Acids 55, 313–323 (2023). https://doi.org/10.1007/s00726-022-03229-2

6. Patel, R. S., Ghasemzadeh, N., Eapen, D. J., Sher, S., Arshad, S., Ko, Y., Veledar, E., Samady, H., Zafari, A. M., Sperling, L., Vaccarino, V., Jones, D. P., & Quyyumi, A. A. (2016). Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease. In Circulation (Vol. 133, Issue 4, pp. 361–369). Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.1161/circulationaha.115.019790

7.  Lu AT, Quach A, Wilson JG, Reiner AP, Aviv A, Raj K, Hou L, Baccarelli AA, Li Y, Stewart JD, Whitsel EA, Assimes TL, Ferrucci L, Horvath S. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY). 2019 Jan 21;11(2):303-327. doi: 10.18632/aging.101684. PMID: 30669119; PMCID: PMC6366976.

8. Liu S, He L, Yao K. The Antioxidative Function of Alpha-Ketoglutarate and Its Applications. Biomed Res Int. 2018 Mar 21;2018:3408467. doi: 10.1155/2018/3408467. PMID: 29750149; PMCID: PMC5884300.

9. Liu, Z., Li, W., Geng, L. et al. Cross-species metabolomic analysis identifies uridine as a potent regeneration promoting factor. Cell Discov 8, 6 (2022). https://doi.org/10.1038/s41421-021-00361-3

10.  Cheng, S., Larson, M., McCabe, E. et al. Distinct metabolomic signatures are associated with longevity in humans. Nat Commun 6, 6791 (2015). https://doi.org/10.1038/ncomms7791

11. Jiang N, Zhao Z. Intestinal aging is alleviated by uridine via regulating inflammation and oxidative stress in vivo and in vitro. Cell Cycle. 2022 Jul;21(14):1519-1531. doi: 10.1080/15384101.2022.2055252.

12. Apparoo Y, Phan CW, Kuppusamy UR, Sabaratnam V. Ergothioneine and its prospects as an anti-ageing compound. Exp Gerontol. 2022 Dec;170:111982. doi: 10.1016/j.exger.2022.111982.

13. Beelman RB, Kalaras MD, Phillips AT, Richie JP Jr. Is ergothioneine a 'longevity vitamin' limited in the American diet? J Nutr Sci. 2020 Nov 11;9:e52. doi: 10.1017/jns.2020.44.

14. https://www.bu.edu/cas/arts-sciences/article/these-bu-chemists-are-looking-to-slow-the-aging-process/

15. Francik R, Krośniak M, Sanocka I, Bartoń H, Hebda T, Francik S. Aronia melanocarpa treatment and antioxidant status in selected tissues in Wistar rats. Biomed Res Int. 2014;2014:457085. doi: 10.1155/2014/457085. Epub 2014 Jun 5. PMID: 25057488; PMCID: PMC4099284.

16. Kim B, Ku CS, Pham TX, Park Y, Martin DA, Xie L, Taheri R, Lee J, Bolling BW. Aronia melanocarpa (chokeberry) polyphenol-rich extract improves antioxidant function and reduces total plasma cholesterol in apolipoprotein E knockout mice. Nutr Res. 2013 May;33(5):406-13. doi: 10.1016/j.nutres.2013.03.001. Epub 2013 Apr 18. PMID: 23684442.

17. Lou-Bonafonte JM, Gabás-Rivera C, Navarro MA, Osada J. The Search for Dietary Supplements to Elevate or Activate Circulating Paraoxonases. Int J Mol Sci. 2017 Feb 15;18(2):416. doi: 10.3390/ijms18020416. PMID: 28212288; PMCID: PMC5343950.