Wednesday, August 20, 2014

Anti-Aging And Paleo

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

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.

(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

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}

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.

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 Nrf2^{23, 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

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!

Casey Thaler, B.A., NASM-CPT, FNS

@EatCleanTClean

Eat Clean Train Clean

http://ift.tt/1jTRsRA

Casey Thaler, B.A., NASM-CPT, FNS is an NASM® certified personal trainer and NASM® certified fitness nutrition specialist. He writes for Paleo Magazine ® and for PaleoHacks. He also runs his own nutrition and fitness consulting company, Eat Clean, Train Clean®. He is pursuing his Ph.D in Nutritional Biochemistry, hopefully from Harvard University.

references

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