“Biohacking” and “longevity” are two popular buzzwords in the dietary supplement industry, while the term “nutrigenomic” is less known. Nevertheless, they all work together to achieve one of the most important nutraceutical strategies available for helping to put more years in your life and life in your years. This was a topic I presented at a SupplySide 2025 education session where there was standing room only. Given the evident interest in this topic, both the editors of Vitamin Retailer and I thought it would be a good idea to revisit it here. So, this is the first part of a two-part article which will take a deep dive into biohacking longevity. Let’s start by explaining some concepts related to this topic, including biohacking, flipping your genetic switches, longevity, gene expression and nutrigenomics.
Biohacking, Flipping Your Genetic Switches and Longevity
Biohacking is a means of do-it-yourself biological “hacks” aimed at improving performance, health and well-being. Flipping your genetic switches refers to using certain nutraceuticals to activate genes that produce substances in your body (i.e., nutrigenomics), helping you achieve these hacks (more on this in the next paragraph). In the context of this article, I’m using the term longevity to mean maintaining a good quality of life and potentially slowing aspects of the aging process. In other words, putting more years in your life and life in your years. So, biohacking longevity incorporates the use of evidence-based dietary nutraceuticals to flip your genetic switches, thereby promoting longevity.
Gene Expression
Many people are surprised that genes do more than just act as a blueprint for creating your body. In fact, genes play an incredibly important role in our bodies on a daily basis via gene expression. So, what is gene expression? Essentially, it is the process by which information encoded in a gene is used to direct the assembly of a protein molecule. A gene is a specific segment of DNA that stores genetic information. RNA, specifically messenger RNA (mRNA), is the molecule transcribed from DNA that carries what is essentially a photocopy of that genetic information to the cell’s protein-making machinery.
Gene expression can be thought of as an “on/off switch” to control the synthesis of RNA molecules and when and where the proteins they make are produced. In addition to the on/off switch, gene expression also acts as a “volume control” to determine how much of those proteins are made. The process of gene expression is carefully regulated, changing substantially under different conditions and cell types. The RNA and protein products of many genes serve to regulate the expression of other genes.1
When a gene is influenced to make more of a given protein, that is referred to as “upregulating” the gene’s expression. When it is influenced to make less of that protein, it is referred to as “downregulating” the gene’s expression. Certain nutraceuticals can help influence gene expression, resulting in some very specific effects on our health and well-being.
Flipping Your Genetic Switch With Nutrigenomics
According to the International Society of Nutrigenetics/Nutrigenomics,2 the way to explain nutrigenomics is to say that nutraceuticals (i.e., vitamins, minerals, herbs or other ingredients found in foods or dietary supplements) can influence gene expression. So, using the previous example of an “on/off switch” and “volume control,” a given nutraceutical can flip on the function of a gene to stimulate the production of a protein, and also help impact the amount of the protein that is made. For example, the nutraceutical can help upregulate a gene that promotes cellular repair—which is obviously a good thing. Likewise, it can downregulate the production of a protein from the same gene, such as one that makes too much of an inflammatory chemical—which may also be a good thing (as in the case of arthritis, for instance). Either way, nutraceuticals that influence gene expression via nutrigenomics can have a meaningful impact on a broad range of biochemicals in our body, and their effect on health, wellness and the aging process.3
Are People Inclined to Use Nutraceuticals for Longevity?
A collaborative survey conducted by National Geographic magazine and AARP posed a question to survey participants: “Would you take a pill that immediately granted 10 bonus years of life?” Not surprisingly, about 75 percent of adults across all age ranges said they would be likely to do so. However, when the question was posed without an age guarantee, instead cited the promise of slower aging with extended health, the likelihood of taking the pill shot up to 85 percent of survey participants responding in the affirmative.4 This is a strong indication that people are interested in considering nutraceuticals for longevity.
Now that you have an understanding of these key concepts, let’s delve into some specific nutraceuticals.
Spermidine
Spermidine is a polyamine, a group of organic compounds having two or more amino groups. Polyamines are synthesized in every living cell and are contained in foods, especially in those considered to contribute to health and longevity.5 As a main polyamine, spermidine plays important roles in cellular growth/health in mammalian cells (including humans) and plants. In the body, the highest concentrations of polyamines are found in the intestine, thymus and liver.6,7 Research has reported that increased polyamine intake (primarily spermidine) over a long period increased blood spermine levels and inhibited aging-associated pathologies and pro-inflammatory status in humans and mice, while also extended life span of mice.8
Autophagy
Cells continually do “housekeeping:” they recycle damaged proteins, worn-out organelles, and other cellular waste through a process called autophagy. Think of it as a self-cleaning mechanism. This is called autophagy (pronounced “ah-TAH-fah-gee”). As we age, autophagy becomes less efficient or slows down, so damaged components build up inside cells.9 That accumulation contributes to dysfunction, stress and eventually to aging at the tissue or organ level.
Spermidine’s big claim to fame is that research10 has shown that it upregulates autophagy.11-14 It does this by impacting genes that regulate cell growth and nutrigenomic regulationa and regulate enzymes that add an acetyl group to histones (a process crucial for making DNA more accessible for its role in producing proteins)b.15 Not surprisingly, research in honeybees has shown that spermidine extended lifespan. It did this by upregulating autophagy-related genesc, as well as genes associated with nutrigenomic changesd.16 Furthermore, the nutrigenomics of spermidine have demonstrated that this polyamine markedly extended the lifespan of yeast, flies and worms, and human immune cells, as well as potently inhibiting oxidative stress in aging mice.17
Epidemiological Research on Spermidine and Lifespan
In a follow-up study of a cohort of 829 participants over 20 years, spermidine showed the strongest inverse relation with mortality among 146 nutrients investigated. This effect was dose-dependent, and the authors explain that spermidine effectively induced autophagy and can reduce the acetylation of histones, which are critical processes for cell homeostasis in aging. In this sense, a diet rich in spermidine, mainly from foods of vegetable origin, was associated with a decrease in the risk of all-cause mortality in the general community.18
Nevertheless, it should be noted that all previous research on spermidine and autophagy is based upon in-vitro, animal or population studies. In other words, there were no published studies showing that a specific amount of spermidine increased markers of autophagy. All of this changed, however, when group of researchers and I published a pilot study on a specific form of spermidine derived from a rice germ extract.
Spermidine as an Autophagy Promoter in Humans
This 56-day study19 examined the effects of spermidine from Miricell rice germ extract (Nutraland USA) on two key biomarkers of autophagy (Beclin-1 and ULK-1) and other unrelated biomarkers as well (more in the next paragraph). The results of this study were that, compared to baseline, 3.3 mg of spermidine from Miricell increased Beclin-1 by 7.3 percent, and ULK-1 by 13.4 percent. Heretofore, this is the first known study on any source of spermidine demonstrating that a specific dose was able to promote autophagy in humans.
In addition, other measures of healthy aging were examined in this study, including the cardiometabolic blood markers for “inflammaging” (a term used to describe chronic, low-grade inflammation that is associated with the aging process) as well as VLDL cholesterol (which can contribute to the buildup of plaque in arteries, increasing the risk of heart disease) and triglycerides (which can also increase the risk of heart disease). In addition to autophagy markers, 3.3 mg of spermidine from Miricell rice germ extract decreased hs-CRP (a blood marker of inflammation) by 20.8 percent, decreased VLDL cholesterol by 20.1 percent, and decreased triglycerides by 26.9 percent.
Telomeres
Chromosomes, the structures that carry our genetic code, have protective “caps” at their ends called telomeres. Every time a cell divides, these caps get a little shorter. Over many divisions, the telomeres gradually shrink until they can no longer protect the chromosome. When that happens, the cell senses unsafe DNA ends, has trouble dividing, or may become dysfunctional. Over time this shortening reduces the ability of tissues to renew, contributing to overall aging. Research on Spermidine for Telomere Length
In research20 on aged mice, six months of supplementation with spermidine in the drinking water protected against a decrease in telomere length. Furthermore, a study21 was conducted to determine the cellular proliferation rate and telomere length in cultures of human adult primary fibroblasts treated with spermidine derived from Miricell rice germ extract. Results of this study were that, under both normal and oxidative conditions, telomere shortening rate was lower in Miricell treated cells than in untreated control cells. These results suggest that telomere shortening is another mechanism of action whereby spermidine may positively impact the aging process.
Conclusion
This was the first part of a two-part article exploring the use of evidence-based nutraceuticals that help to biohack longevity. In this part, I only examined the impact of spermidine. In the second part (to be published in the February issue of Vitamin Retailer), I’ll review other evidence-based nutraceuticals that can be used for this same purpose.VR
References:
a E1A-binding protein p300.
b HAT enzymes like Iki3p and Sas3p, and α-tubulin acetyltransferase.
c ATG3, 5, 9, and 13.
d HDAC1, HDAC3, SIRT1, KAT2A, KAT6B, P300, DNMT1A, DNMT1B.
1 Brody L. Gene Expression. National Human Genome Research Institute. Updated: July 2, 2025. Retrieved July 2, 2025 from www.genome.gov/genetics-glossary/Gene-Expression.
2 www.isnn.info.
3 Mutch DM, Wahli W, Williamson G. FASEB J. Nutrigenomics and Nutrigenetics: The Emerging Faces of Nutrition. 2005;19:1602–1616.
4 Harrar S. It’s Time to Throw Out Stereotypes on Aging. Washington, DC: AARP. June 6, 2022. Retrieved December 14, 2022 from www.aarp.org/health/healthy-living/info-2022/aging-survey.html.
5 Muñoz-Esparza NC, Latorre-Moratalla ML, Comas-Basté O, Toro-Funes N, Veciana-Nogués MT, Vidal-Carou MC. Polyamines in Food. Front Nutr. 2019 Jul 11;6:108.
6 Larqué E, Sabater Molina M, Zamora S. Biological significance of dietary polyamines. Nutrition. 2007; 23:87–95. 7 Ruíz Cano D, Pérez Llamas F, Zamora S. Implicaciones de las poliaminas en la salud infantil. Arch Argent Pediatr. 2012; 110:244–50.
8 Soda K. Overview of Polyamines as Nutrients for Human Healthy Long Life and Effect of Increased Polyamine Intake on DNA Methylation. Cells. 2022 Jan 4;11(1):164.
9 Autophagy. Cleveland Clinic. Last reviewed by a Cleveland Clinic medical professional on 08/23/2022. Retrieved May 24, 2023 from https://my.clevelandclinic.org/health/articles/24058-autophagy#:~:text=Autophagy percent20allows percent20your percent20body percent20to,potentially percent20preventing percent20and percent20fighting percent20disease.
10 Pietrocola F, Lachkar S, Enot DP, Niso-Santano M, Bravo-San Pedro JM, Sica V, Izzo V, Maiuri MC, Madeo F, Mariño G, Kroemer G. Spermidine induces autophagy by inhibiting the acetyltransferase EP300. Cell Death Differ. 2015 Mar;22(3):509-16.
11 Handa AK, Fatima T, Mattoo AK. Polyamines: bio-molecules with diverse functions in plant and human health and disease. Front Chem. 2018; 6:10.
12 Eisenberg T, Knauer H, Schauer A, Buttner S, Ruckenstuhl C, Carmona-Gutierrez D, et al. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol. 2009; 11:1305–14.
13 Kiechl S, Pechlaner R, Willeit P, Notdurfter M, Paulweber B, Willeit K, et al. Higher spermidine intake is linked to lower mortality: a prospective population-based study. Am J Clin Nutr. 2018; 108:371–80.
14 Soda K. Spermine and gene methylation: a mechanism of lifespan extension induced by polyamine-rich diet. Amino Acids. 2020 Feb;52(2):213-224.
15 Satarker S, Wilson J, Kolathur KK, Mudgal J, Lewis SA, Arora D, Nampoothiri M. Spermidine as an epigenetic regulator of autophagy in neurodegenerative disorders. Eur J Pharmacol. 2024 Sep 15;979:176823. doi: 10.1016/j.ejphar.2024.176823. Epub 2024 Jul 18. PMID: 39032763.
16 Kojić D, Spremo J, Đorđievski S, Čelić T, Vukašinović E, Pihler I, Purać J. Spermidine supplementation in honey bees: Autophagy and epigenetic modifications. PLoS One. 2024 Jul 1;19(7):e0306430. doi: 10.1371/journal.pone.0306430. PMID: 38950057; PMCID: PMC11216588.
17 Eisenberg T, Knauer H, Schauer A, Büttner S, Ruckenstuhl C, Carmona-Gutierrez D, Ring J, Schroeder S, Magnes C, Antonacci L, Fussi H, Deszcz L, Hartl R, Schraml E, Criollo A, Megalou E, Weiskopf D, Laun P, Heeren G, Breitenbach M, Grubeck-Loebenstein B, Herker E, Fahrenkrog B, Fröhlich KU, Sinner F, Tavernarakis N, Minois N, Kroemer G, Madeo F. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol. 2009 Nov;11(11):1305-14. doi: 10.1038/ncb1975. Epub 2009 Oct 4. PMID: 19801973.
18 Kiechl S, Pechlaner R, Willeit P, Notdurfter M, Paulweber B, Willeit K, et al. Higher spermidine intake is linked to lower mortality: a prospective population-based study. Am J Clin Nutr. 2018; 108:371–80.
19 Ziegenfuss TN, La Monica M, Bruno G. Effects of Spermidine-Rich Rice Germ Extract Supplement on Biomarkers of Healthy Aging and Autophagy – A proof of Concept Pilot Study. Altern Ther Health Med. 2025 Aug 28:AT11706. Online ahead of print.
20 Wirth A, Wolf B, Huang CK, Glage S, Hofer SJ, Bankstahl M, Bär C, Thum T, Kahl KG, Sigrist SJ, Madeo F, Bankstahl JP, Ponimaskin E. Novel aspects of age-protection by spermidine supplementation are associated with preserved telomere length. Geroscience. 2021 Apr;43(2):673-690.
21 Study Report for Nutraland: In-vitro proliferative and telomere length analysis (TAT). LifeLength. January 17, 2023: 23 pgs.
Gene Bruno, DBM, MS, RH(AHG) Professor Emeritus of Nutraceutical Science, is a writer, educator and a nutraceutical scientist with more than 45 years of experience educating natural product retailers and health care professionals and formulating natural products for dozens of dietary supplement companies. He has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications. Bruno also hosts “The Vitamin Professor Podcast” brought to you by VRM Media. He can be reached at [email protected].
