Anti-Aging And Paleo

Anti-Aging And Paleo | The Paleo Diet

A hypothetical ‘fountain of youth’ has long been a sought-after commodity.1 Researchers have looked at elements as disparate as vitamin D,2 DHEA,3 and telomerase4 among many others, in order to try and prevent nature from taking its course.5

New and exciting discoveries in the scientific field aside, it is important to note that a healthy lifestyle is the number one way to prevent both disease and aging.6 In fact, oncologists found of all cancer-related deaths, as many as 30–35% are linked to diet.7

Anti-Aging Figure 1

Cancer deaths (%) linked to diet as reported by Willett

Many mechanisms induce the process of aging,8 including the gene, TAp63, as a possible critical element.9 Described as a ‘master transcriptional regulator of lipid and glucose metabolism,’10 the theory has merit.

Anti-Aging Figure 2

(A) TAp63 maintains adult stem cells (ASC) by transcriptionally activating p57 and repressing Ink4a/Arf, preventing premature aging. (B) In the absence of TAp63, p57 mRNA levels are low, leading to hyperproliferation of ASCs (shown in pink), and Ink4a/Arf levels are high, resulting in a concomitant senescence of ASCs (shown in blue) and a premature aging phenotype in TAp63 deficient mice. The interplay of the p53 family, including TAp73, ΔNp73, and ΔNp63, remains to be elucidated.

High docosahexaenoic acid (DHA) content combats the aging process, placing wild-caught fish near the top of the list.11 One anti-aging mechanism via which omega-3’s (such as DHA) operate, is through nuclear factor erythroid 2-related factor 2 (Nrf2).12 Nrf2 is a master transcriptional factor for antioxidant genes,13 and vital for many processes in the body.14

Interestingly, researchers found that DHA, but not EPA, markedly increased intracellular 4-HHE, and nuclear expression and DNA binding of Nrf2.15 This lends further support to evidence DHA’s superiority to EPA.16 DHA has also been shown to have neuroprotective effects,17 increasingly important in neurodegenerative diseases, like Alzheimer’s.18

Anti-Aging Figure 2

Docosahexaenoic acid (DHA) and its neuroprotective properties. Affect on amyloid plaque formation and aggregation, improves cerebral blood flow and reduces inflammation.

Researchers also identified dietary flavonoids as important activators of the Nrf2 system.19 Flavonoids are present in large amounts in citrus fruit, berries, olive oil, apples, red wine, tea, grapes, chocolate, and cocoa.20, 21, 22

Anti-Aging figure 3

Schematic representation depicting some of the various cytoprotective proteins that are upregulated by Nrf2. Flavonoid-mediated protection from ischemic/hemorrhagic stroke, traumatic brain injury, and/or other neuropathies may result in large part from Nrf2 regulation of these pathways.

Anti-aging figure 4

Schematic representation depicting the potential mechanisms by which flavanol-mediated Nrf2 induction leads to activation of cytoprotective pathways after stroke, traumatic brain injury, and/or other neurodegenerative diseases. Flavanols may induce Nrf2 through binding to receptors seated on the plasma membrane and subsequent initiation of intracellular signaling cascades. Alternatively, passive diffusion or active transport through the plasma membrane may permit direct cytosolic dissociation of the Keap1/Nrf2 complex or activation of second messengers that regulate Nrf2 translocation into the nucleus. Upon nuclear translocation, Nrf2 binds to AREs on the promoter regions of cytoprotective genes to regulate heme/biliverdin, glutathione, NAD(P)H, and/or other protective pathways.

Fasting and caloric restriction activate Nrf223, 24 as well. Since Nrf2 has been shown to help with longevity, metabolic regulation and also responds to nutritional input,25 its importance in anti-aging cannot be overstated.26

Anti-Aging Figure 5

Model: Nrf2 as a convergence point for stress, metabolic, and longevity signals

Perhaps unsurprisingly, there have also been studies that show consumption of alcohol and caffeine actually alter telomeres.27 Telomeres protect chromosome ends from degradation and play crucial roles in cellular aging and disease.28 This is further proof that a Paleo lifestyle can help protect against aging.29, 30

Out of all aging-related mechanisms, the most interesting may be a protein named GDF11, which appears to cause a reversal of many signs of aging.31 GDF11 normally declines with age, but when levels are restored, GDF11 shows benefits to multiple tissues.32 The idea of a novel approach to not only reverse muscular aging, but also brain aging, is tantalizing.33

But remember, while scientific advances are exciting, they are still years away from being proven in humans, and/or are limited in implementation. Therefore, a healthy lifestyle is still the number one way to prevent both disease and aging. A Paleo Diet, which is by nature high in flavonoids, low in inflammation and rich in nutrients, is a great choice. A Paleo lifestyle, with regular physical activity, fun, and high quality sleep, will keep you looking and feeling young, for many decades to come!


1. Haber C. Life extension and history: the continual search for the fountain of youth. J Gerontol A Biol Sci Med Sci. 2004;59(6):B515-22.

2. Binkley N. Is vitamin D the fountain of youth?. Endocr Pract. 2009;15(6):590-6.

3. Leowattana W. DHEA(S): the fountain of youth. J Med Assoc Thai. 2001;84 Suppl 2:S605-12.

4. De magalhães JP, Toussaint O. Telomeres and telomerase: a modern fountain of youth?. Rejuvenation Res. 2004;7(2):126-33.

5. Solana R, Alonso MC, Peña J. Natural killer cells in healthy aging. Exp Gerontol. 1999;34(3):435-43.

6. Arab L, Sabbagh MN. Are certain lifestyle habits associated with lower Alzheimer’s disease risk?. J Alzheimers Dis. 2010;20(3):785-94.

7. Anand P, Kunnumakkara AB, Kunnumakara AB, et al. Cancer is a preventable disease that requires major lifestyle changes. Pharm Res. 2008;25(9):2097-116.

8. Partridge L, Gems D. Mechanisms of ageing: public or private?. Nat Rev Genet. 2002;3(3):165-75.

9. Su X, Flores ER. TAp63: The fountain of youth. Aging (Albany NY). 2009;1(10):866-9.

10. Su X, Gi YJ, Chakravarti D, et al. TAp63 is a master transcriptional regulator of lipid and glucose metabolism. Cell Metab. 2012;16(4):511-25.

11. Miller MR, Nichols PD, Carter CG. n-3 Oil sources for use in aquaculture–alternatives to the unsustainable harvest of wild fish. Nutr Res Rev. 2008;21(2):85-96.

12. Yang YC, Lii CK, Wei YL, et al. Docosahexaenoic acid inhibition of inflammation is partially via cross-talk between Nrf2/heme oxygenase 1 and IKK/NF-κB pathways. J Nutr Biochem. 2013;24(1):204-12.

13. Leonard MO, Kieran NE, Howell K, et al. Reoxygenation-specific activation of the antioxidant transcription factor Nrf2 mediates cytoprotective gene expression in ischemia-reperfusion injury. FASEB J. 2006;20(14):2624-6.

14. Kumar H, Kim IS, More SV, Kim BW, Choi DK. Natural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases. Nat Prod Rep. 2014;31(1):109-39.

15. Ishikado A, Morino K, Nishio Y, et al. 4-Hydroxy hexenal derived from docosahexaenoic acid protects endothelial cells via Nrf2 activation. PLoS ONE. 2013;8(7):e69415.

16. Conquer JA, Holub BJ. Dietary docosahexaenoic acid as a source of eicosapentaenoic acid in vegetarians and omnivores. Lipids. 1997;32(3):341-5.

17. Shimazawa M, Nakajima Y, Mashima Y, Hara H. Docosahexaenoic acid (DHA) has neuroprotective effects against oxidative stress in retinal ganglion cells. Brain Res. 2009;1251:269-75.

18. Yurko-mauro K, Mccarthy D, Rom D, et al. Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement. 2010;6(6):456-64.

19. Leonardo CC, Doré S. Dietary flavonoids are neuroprotective through Nrf2-coordinated induction of endogenous cytoprotective proteins. Nutr Neurosci. 2011;14(5):226-36.

20. Beecher GR. Overview of dietary flavonoids: nomenclature, occurrence and intake. J Nutr. 2003;133(10):3248S-3254S.

21. Hollman PC, Katan MB. Dietary flavonoids: intake, health effects and bioavailability. Food Chem Toxicol. 1999;37(9-10):937-42.

22. Yao LH, Jiang YM, Shi J, et al. Flavonoids in food and their health benefits. Plant Foods Hum Nutr. 2004;59(3):113-22.

23. Ungvari Z, Parrado-fernandez C, Csiszar A, De cabo R. Mechanisms underlying caloric restriction and lifespan regulation: implications for vascular aging. Circ Res. 2008;102(5):519-28.

24. Zhang YK, Wu KC, Klaassen CD. Genetic activation of Nrf2 protects against fasting-induced oxidative stress in livers of mice. PLoS ONE. 2013;8(3):e59122.

25. Sykiotis GP, Habeos IG, Samuelson AV, Bohmann D. The role of the antioxidant and longevity-promoting Nrf2 pathway in metabolic regulation. Curr Opin Clin Nutr Metab Care. 2011;14(1):41-8.

26. Lewis KN, Mele J, Hayes JD, Buffenstein R. Nrf2, a guardian of healthspan and gatekeeper of species longevity. Integr Comp Biol. 2010;50(5):829-43.

27. Romano GH, Harari Y, Yehuda T, et al. Environmental stresses disrupt telomere length homeostasis. PLoS Genet. 2013;9(9):e1003721.

28. Aubert G, Lansdorp PM. Telomeres and aging. Physiol Rev. 2008;88(2):557-79.

29. Erickson KI, Gildengers AG, Butters MA. Physical activity and brain plasticity in late adulthood. Dialogues Clin Neurosci. 2013;15(1):99-108.

30. Lau FC, Shukitt-hale B, Joseph JA. Nutritional intervention in brain aging: reducing the effects of inflammation and oxidative stress. Subcell Biochem. 2007;42:299-318.

31. Sinha M, Jang YC, Oh J, et al. Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle. Science. 2014;344(6184):649-52.

32. Bitto A, Kaeberlein M. Rejuvenation: It’s in Our Blood. Cell Metab. 2014;20(1):2-4.

33. Katsimpardi L, Litterman NK, Schein PA, et al. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science. 2014;344(6184):630-4.

Comments to this website are moderated by our editorial board. For approval, comments need to be relevant to the article and free of profanities and personal attacks. We encourage cordial debates for the betterment of understanding and discovery. Comments that advertise or promote a business will also not be approved, however, links to relevant blog posts that follow the aforementioned criteria will be allowed. Thank you.

“1” Comments


Leave a Reply

Your email address will not be published. Required fields are marked *

Affiliates and Credentials