How Not to Age: The Scientific Approach to Getting Healthier as You Get Older

by Michael Greger

cup of corn and a half cup of spinach a day—most individuals saw a dramatic boost in protective macular pigmentation within the first month.6555 Three months after the subjects stopped eating the corn and spinach, the levels of these pigments remained relatively high, indicating that once we build up our macular pigment with a healthy diet, our eyeballs really try to hold on to it. So, even if we go on vacation and end up eating more iceberg lettuce than spinach, our eyes will try to hold out until we get back. Yellow corn has about seventy times more lutein than white corn,6556 but spinach has sixty times more than yellow corn. Corn beats greens for zeaxanthin, though.

However, a few food sources can crack corn. Orange bell peppers have eight times more zeaxanthin than corn,6557 but goji berries reign supreme, with about twelve times more than orange peppers.6558 In see.nf/gojis, I profile a double-blind, randomized, placebo-controlled study that found that gojis may even help people already suffering from macular degeneration.

Goji berries may cost about twenty dollars per pound in natural foods stores, but they’re even cheaper than raisins in Asian supermarkets, where you can buy them as “Lycium” berries. I encourage you to swap out raisins for goji berries—in your breakfast oatmeal, as a snack, in muffins, and anywhere else. As one review concluded, goji berries offer a “‘whole food’ dietary supplement for the maintenance of retinal health as well as for prevention and/or delay in progression of retinal diseases commonly seen in clinical practice.

Lutein and zeaxanthin are both fat-soluble, so make sure you pair your greens with nuts, seeds, nut and seed butters, or any other Green Light source of fat. They’ll taste better, and you’ll maximize absorption of these important macular pigments.

I run through all the experiments showing how pairing avocados with salsa or salads can dramatically increase the absorption of the carotenoids in vegetables.

with a significantly increased risk of developing macular degeneration.6579 Those with higher cholesterol intake have up to 60 percent higher odds of early age-related macular disease, and higher saturated fat consumption bumps it up to 80 percent.

Drusen, the spots of debris in the back of the eye that are the hallmark of macular degeneration, are actually cholesterol-rich deposits with a composition similar to that of atherosclerotic plaques in arteries.

In addition to two to three daily servings of green leafy vegetables, berries are considered a healthy choice for conserving our eyesight.

a tiny daily pinch of saffron (20 mg) can cause a significant, yet modest, improvement in visual acuity in older adults with mild or moderate age-related macular degeneration.

Japanese researchers have shown that black currant pigments can slow down glaucoma vision loss. (Details in see.nf/currants.) This was accompanied by an increase in ocular blood flow, but no change in intraocular pressure, suggesting that berries might also work for “normal tension” glaucoma, the type in which the optic nerve deterioration proceeds despite normal eyeball pressure.6605 Note that most “currants” sold in the United States are little raisins (Vitis vinifera) and not actual currants (Ribes nigrum), which were illegal to grow until recently, due to pressure from the lumber industry because they can carry white pine blister rust.

Cataracts are a direct result of oxidative stress,6617 free radical damage to the normally transparent crystallin proteins that make up the lenses in our eyes.

Those eating diets with a higher total antioxidant content do tend to have lower risk of age-related cataract.

The same could be said for the intake of some individual antioxidants—vitamin C, beta-carotene, and lutein and zeaxanthin—

In addition to antioxidant-rich foods,6636 eating more anti-inflammatory foods is also associated with lower cataract risk.6637 As well, the aging toxin AGEs (see here) may accelerate cataract formation by cross-linking lens proteins.

Hospice is often framed as “giving up,” but, ironically, when you compare hospice versus nonhospice patient survival, the patients in hospice actually tend to live longer.

Surprisingly, not a single one of dozens of studies adding an average of hundreds of calories of nuts a day for fifteen weeks to people’s diets resulted in significant weight gain.6768 However, there is a limit. Do not regularly eat more than a cup of nuts a day for the same reason we should avoid consuming multiple cups of spinach, beet greens, or Swiss chard, more than a few starfruits,6769 multiple cups of rhubarb,6770 or even spoonsful of chaga mushroom powder6771 a day: oxalates.

the longevity benefits associated with nuts (including peanuts) do not appear to extend to peanut butter, perhaps due to the lack of intact cellular structures that deliver a bounty of prebiotic goodness to our friendly gut flora. (See here.) The healthiest nut, however, is probably walnuts. Not only do they have some of the highest antioxidant6777 and omega-36778 levels, but walnuts are the only nuts known to significantly improve artery function,6779 and they beat out others in suppressing cancer cell growth in vitro.

Nuts seem to beat out vegetables in terms of food groups associated with a longer life, but that was compared to vegetables in general. Green leafy vegetables can match nuts for potentially decreasing the risk of premature death,6785 and consumption of greens is also associated with lower risk of heart disease, stroke, and a few types of cancer and may even help prevent some of the leading causes of age-related vision loss.6786 (See the Preserving Your Vision chapter.) Greens can also boost our immunity, slow our metabolism, and protect our body against the effects of air pollution, one of the leading causes of death worldwide.

The immune boost we get from consuming broccoli and other cruciferous vegetables not only protects us against pathogens found in food but also against pollutants in the environment, like car exhaust or tobacco smoke. Because dioxins and certain other pollutant chemicals exert their toxic effects through the Ah receptor system, cruciferous compounds may block them.

Anthocyanin comes from the Greek anthos, meaning “flower,” and kyanos, meaning “blue.”6927 The same pigments color red, blue, and purple berries, but their names still hint at their floral origins—for example, the petunidin in blueberries or the peonidin in cranberries.6928 Able to cross the blood-brain barrier, anthocyanins are thought to be responsible for the cognitive benefits of berries in terms of improving brain perfusion, memory, executive function, processing speed, attention, and overall cognitive performance.6929 They may also benefit our eyesight.

controlled trials have shown that berry anthocyanins can significantly improve both objective and subjective signs and symptoms of eye strain,6930 as well as improving light6931 and dark6932 adaptation. Anthocyanins appear to be important for regenerating a receptor protein known as “visual purple” in our retina that helps convert light into electrical signals for the brain, speeding up how fast our vision can adjust to changing light levels.

As discussed in the Inflammation chapter, berries have systemic anti-inflammatory effects throughout the body, though they can also suppress inflammation directly within the gut.6934 Ninety percent of patients with ulcerative colitis responded to bilberries, with most achieving remissions within six weeks; disease activity surged back, however, once the berries were stopped.6935 Part of this may derive from the prebiotic effect of anthocyanins on the gut flora. Eating berries increases the number of good bugs and decreases the number of bad ones.6936 For example, eating blueberries every day increases the number of Lactobacilli and Bifidobacteria.6937 Similar effects have been shown for black currants6938 and tart cherries.6939

Anthocyanins are cleared from our bloodstream within about six hours, so, by the afternoon, the berries you had on your oatmeal may have run their course.6953 In my mind, berries make the perfect dessert for any meal. There are other anthocyanin-containing fruits, like plums, pomegranates, and red or black grapes.

For a drink, what do you think makes hibiscus tea as ruby red as Dorothy’s slippers? Anthocyanins may also be responsible for the blood-pressure-lowering benefits of hibiscus.

For about half a century, we’ve known that tart cherries are so anti-inflammatory that they may be used to successfully treat gout, a painful type of arthritis, as I mentioned in the Inflammation chapter.6957 Cherries can also reduce inflammation in healthy people, as indicated by decreasing C-reactive protein levels.

Whatever you now do with raisins, do it with gojis instead. Domesticated more than 6,000 years ago,6968 the grapevine is now the single largest fruit crop grown in the world.6969 What can they do for us? A meta-analysis of more than fifty randomized controlled trials involving thousands of study participants found that various grape products can cause a small (five-point) drop in LDL cholesterol, but raisins did not seem to work.

Similarly, raisins were not able to acutely improve artery function,6972 but a cup and a quarter of various fresh grapes, including red and blue-black ones, can even blunt the arterial dysfunction caused by a McDonald’s Sausage McMuffin with Egg meal.6973 Chronic improvement in artery function was also demonstrated in a randomized, double-blind, placebo-controlled trial (using powdered red grapes).

grapes with seeds, which harbor the bulk of the polyphenols in the fruit. Only 1 percent is found in the pulp and 5 percent in the juice. The skins of grapes hold 30 percent of the polyphenols, but the seeds contain the remaining 64 percent.

Xenohormesis and microRNAs represent cross-kingdom communication pathways between plants and animals that we may be able to use to our advantage.

Hormesis can be thought of as the “that which doesn’t kill you makes you stronger” principle.6976 Physical activity is the classic example:6977 You put stress on your muscles and heart, and are all the healthier for it, provided there is sufficient recovery time. Mild stresses like exercise can trigger a protective response that leads to strengthened defenses in the long run.

Hormesis takes the notion “too much of a good thing can be bad” and turns it on its head by suggesting that, sometimes, a little of a bad thing can be good.6981 Hormesis comes from the Greek term hormáein, meaning “to excite.”6982 Rather than a linear model in which there are small effects at small doses and the same but larger effects at larger doses, hormesis describes a biphasic response characterized by one effect at a low dose and the opposite effect at a higher dose. For example, herbicides kill plants, but in tiny doses they can actually boost plant growth, presumably by stressing the plant into rallying its resources to successfully fight back.

There are, however, salutary ways to harness hormesis for health and longevity.

classic hormesis, where low levels of damage can upregulate protective mechanisms and ultimately leave you better off.

Hormesis may be why dietary restriction can lead to lifespan extension.6998 The mild stress placed upon the body by not eating enough may activate a wide variety of protective pathways, ramping up anti-inflammatory and antioxidant defenses.6999 Your body is preparing itself for the coming famine it thinks is about to occur.

xenohormesis, derived from the Greek xenos, meaning “stranger,” “foreigner,” or “other.” Xenohormesis refers to the bestowal of stress resistance from stressed plants to the animals who eat them.

We can just let the plants get stressed because, incredibly, the stress response molecules in plants may activate the same protective responses in us.7011 The majority of known health benefits of edible plants may be attributable to the pharmacologically active substances of plants’ sophisticated stress responses, off which we can then piggyback. For example, I’ve often mentioned polyphenols, a class of phytonutrients for which there’s a huge medical literature on health-promoting effects.7012 Plants produce polyphenols to protect themselves,7013 and we may be able to expropriate and commandeer them for our own similar purpose.7014 Xenohormesis explains how environmentally stressed plants produce bioactive compounds that can confer survival benefits to those of us who consume them. Drought-stressed strawberries, for example, have more antioxidants and other phytonutrients. Have you ever eaten a wild strawberry? The taste is incomparable to the flat flavor facade of the cultivated kind. The healthiest grapes often grow in relatively dry, sun-exposed, infertile soil.7015 Studies show that commonly consumed fruits and vegetables can be nutritionally enhanced by light, water, nutrient deficits, cold stress, or being nibbled on by bugs.7016 That may help explain why the levels of phytonutrients are estimated to be 10 to 50 percent higher in organic vegetables compared with conventionally grown ones.

If you starve plants, they do the same thing mammals do: activate preservation pathways. So, let the plants face the adversity to create the molecules that trigger cell stress resistance, alter metabolism, and improve disease resistance. Then, we can just capture them for the same uses in our own body. The fact that many phytonutrients act as “dietary restriction mimetics,” in that they mimic the physiological effects of dietary restriction, may be no coincidence. The plants produce these compounds to save their own green butts from scarcity. So, instead of having to starve, thanks to xenohormesis, we may be able to let plants bear the brunt and enable us to harness their hardships as a means to promote our own health.

Polyphenols are among the front-runners in developing dietary approaches to fight age-associated diseases. More than 8,000 different polyphenols have been identified, but only a small proportion have had their health effects cataloged.7040

one source of flavonoids associated with an increased mortality: grapefruit, chalked up in part to grapefruit’s suppression of a set of detoxification enzymes in our intestines.

If phytonutrients can be so healthful, why not just take plant extract supplements rather than go to all the trouble of eating the plants themselves? Besides the misidentification, contamination, and adulteration issues rife within the poorly regulated supplement market7058 we’ve discussed, there is a question of dose. Taking polyphenol supplements can result in blood levels nearly an order of magnitude higher than that of a polyphenol-rich diet.7059 When it comes to hormesis, less may be more.

For a series of examples of how isolated phytochemicals and plant extracts can be life-extending at one dose but life-shortening at a higher one, check out see.nf/dosing. After all, many flavonoids function as “nature’s pesticides,” protecting plants from predators like us.

Each plant not only has thousands of different phytonutrients, but very different phytonutrient profiles.7078 So, there may be synergistic effects when eating different foods together, too.7079 The reason it’s better to get vitamin C in citrus form than pill form is that you won’t miss out on all those citrus phytonutrients, like lemonin, limonol, or tangeretin,

Combining foods across different categories appears to increase the likelihood of synergy.7080

While individual plant compounds had little or no effect on their own, in combination, dietary blood levels significantly suppressed breast cancer cell proliferation by more than 80 percent, inhibited cancer cell migration and invasion, stopped the cancer cells in their tracks, and eventually killed them all off. All the while, this “phytochemical super-cocktail” had no deleterious effects on the normal, noncancerous cells used as control.

Though there are generic plant compounds like vitamin C that are found scattered throughout the plant kingdom, there are also specific phytonutrients produced by specific plants to perform specific functions—both in their organs and in ours.7086 We miss out on these if we’re stuck in a fruit and vegetable rut, even if we’re eating many servings a day.

The researchers concluded that “smaller amounts of many phytochemicals may have greater potential to exert beneficial effects than larger amounts of fewer phytochemicals.” Observational studies have also found that fruit and vegetable variety is associated with lower inflammation7090 and better cognition7091—again, independent of quantity.

If you thought the interspecies communication between the plant and animal kingdoms with xenohormesis was interesting, hold on to your hat. The “Central Dogma” of molecular biology has been challenged by a revolutionary twenty-first-century discovery: microRNAs.

Understanding microRNA regulation is particularly insightful7107 because a single microRNA can block more than a thousand different messenger RNAs.7108 So, one microRNA can effectively silence more than a thousand different genes. In my building analogy, one simple instruction can put all the second-floor workers on hold until the first-floor workers finish construction. Then, there are regulators who regulate the regulators, other noncoding RNAs that stop the microRNAs from stopping the messenger RNAs,7109 but let’s not even go there.

MicroRNAs have been found circulating in at least twelve different human bodily fluids.7112 (When I read that, I had to stop and think, Wait. Can I even name a dozen bodily fluids?) We didn’t think this possible since we have enzymes that chop up any floating RNA outside our cells (as a precaution against viruses, which often come bearing RNA). It turns out they’re being transported in exosomes, tiny bubble-like vessels that pinch off from cells. We used to think these budding blebs were just a waste disposal device for the cells.7113 (Why do scientists seem to just jump to junk when they don’t understand something?) But, in 2007, we discovered that they were packed with microRNA.7114 Our cells were communicating with each other! In this way, a liver cell could send out microRNAs to regulate the genes in a lung cell, which could then regulate a brain cell, or vice versa. They could even talk to the next generation by depositing their microRNA load into a sperm or egg cell.

What’s the upshot of all this? It is now safe to say that microRNAs probably regulate virtually every biological process, playing essential roles in virtually every aspect of health.