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

by Michael Greger

Plants make antioxidants so we don’t have to. Since antioxidant-rich foods traditionally formed such a major part of our ancestral diet, we didn’t have to evolve that great of an antioxidant system. We could just let the plants in our diet pull some of the weight, like giving us vitamin C so we didn’t have to be bothered to make it ourselves.1524 Using plants as a crutch may well have relieved the pressure for further evolutionary development of our own defenses. So, we became dependent on getting massive quantities of plant foods in our diet, and, when we don’t, we may suffer adverse health consequences.

Among plant foods, berries average about ten times the antioxidant power of other fruits and vegetables, and are beat out only by herbs and spices. Cherries may have up to 714 units,

antioxidant levels can plummet within two hours of a stressful event and may take up to three days to get back to normal.1550 Hours to lose, but days to recover, so healthier eating is especially important when we anticipate we’ll be stressed, sick, or tired. Ideally, we would be having antioxidant-rich foods at every meal and snack.

The blueberries significantly reduced the ensuing DNA damage within an hour of consumption. However, the protective effect was transient. DNA vulnerability returned within two hours, so again, we should aim to eat supercharged antioxidant-rich foods multiple times a day.

There are, however, foods that have been demonstrated to reduce DNA damage when actually eaten: one daily ounce of mixed nuts (walnuts, almonds, and hazelnuts) can reduce damage within twelve weeks,1555 five teaspoons a day of tomato paste within just two weeks,

Kiwis,1569 cooked carrots,1570 and green tea1571 have the additional distinction of being able to facilitate DNA repair, something previously presumed not to be readily affected by diet.

The leader of the pack? Cloves.

single typically salted meal can significantly suppress artery function within thirty minutes1605 by suppressing a powerhouse antioxidant enzyme in our body called superoxide dismutase,1606 which can ordinarily detoxify a million free radicals per second.

Given the hormetic benefits of certain mild pro-oxidant stresses, such as green tea and physical activity, the oversimplistic narrative of “antioxidants good, free radicals bad”1640 must be revised.

Nrf2 is considered the “master regulator of the environmental stress response”1654 and is expressed universally in all cells,1655 just waiting to be freed to hit the panic button and rally cellular defenses. Nrf2 is also called a “guardian of healthspan and gatekeeper of species longevity.

For example, the Nrf2 gene is overexpressed sixfold in long-lived naked mole rats compared to mice,1660 combined with lower suppressor protein expression.1661 That may not only help explain why they live eight times longer1662 but also why it takes up to a hundred times the concentration of toxins like heavy metals and chemotherapy drugs to kill the same percentage of skin cells taken from naked mole rats compared to mice.1663 They are little nude detoxification machines. Unfortunately, Nrf2 levels1664 and signaling tend to decrease with age.

the most potent natural Nrf2 inducer on the planet may be sulforaphane,1667 the compound formed when we bite into cruciferous vegetables, such as broccoli, kale, collards, cabbage, and cauliflower. Sulforaphane, like the active components of green tea and turmeric, frees Nrf2 by oxidizing its suppressor protein, resulting in a rejuvenating effect

Nrf2 activation led to decreased DNA damage and muscle loss, and improved heart function and lifespan.

sulforaphane can delay the senescence of human stem cells.

Enhancing Sulforaphane Formation Acidifying raw cruciferous vegetables can boost sulforaphane formation. Adding lemon juice to a shredded cabbage salad, for instance, may help a little, but adding vinegar is even better, presumably because of its higher acid content.

The most critical factor when it comes to cooking, though, is pausing between chopping and heating, my “hack and hold” strategy

Too much cholesterol in the blood has long been considered to be a primary risk factor for developing Alzheimer’s disease.

Cholesterol cannot directly get across the blood-brain barrier,1716 though, but cholesterol oxidation products (COPs) can. Also known as oxysterols, oxidized cholesterol present in the bloodstream accumulates in the brain,

COPs can be up to a hundred times more toxic than unoxidized cholesterol.1719 They may contribute to a wide range of age-related diseases, including atherosclerosis,1720 cataracts,1721 kidney failure,1722 osteoporosis,1723 and cancer.

Only foods that start out with cholesterol can end up with oxidized cholesterol.1741 So, the primary method to reduce dietary intake may be to reduce the total cholesterol content of the diet by centering one’s diet around unprocessed plant foods, which don’t have any cholesterol to get oxidized in the first place.

Coenzyme Q10, more commonly known as CoQ10, is the only fat-soluble antioxidant produced by the human body.1752 Because we synthesize it from scratch, there’s no need to consume any,

In people, CoQ10 supplementation reduces markers of inflammation1759 and oxidative stress1760

Those who choose to take it need to keep it in a cool, dark, airtight container since it’s sensitive to heat, light, and oxidation.

Selenium, a critical component of key antioxidant enzymes, is considered an essential trace mineral,1778 though, given its narrow safety margin, it’s also been termed an “essential poison.”1779 Indeed, the consumption of just a single high-selenium Brazil nut a day was found to have pro-inflammatory effects.

The mitochondrial theory of aging explains why animals with the lowest rate of free radical production live the longest. We can slow this rate through exercise training and methionine restriction, which can be achieved with a predominantly whole food, plant-based diet.1797 Such an eating pattern would also cut down on pro-oxidant foods rich in cholesterol, salt, saturated fat, and sugar, while boosting the intake of plant foods that have the dual benefit of enhancing our primary oxidant defense via Nrf2 activation

Each of us contains tens of billions of miles of DNA—enough for 100,000 trips to the moon and back if each strand were uncoiled and placed end to end.1798 How does our body prevent these precious ribbons of information from getting all twisted and tangled? Enzymes known as sirtuins keep our DNA neatly and nicely wrapped around spool-like proteins and, by doing so, silence whatever genes are in that stretch of DNA. The name SIRtuins stands for Silencing Information Regulator.

In addition to preserving DNA integrity,1808 sirtuin activation improves DNA repair,1809 downregulates inflammation,1810 and contributes to telomere maintenance,

The way AMPK enhances sirtuin activity is by increasing levels of cellular nicotinamide adenine dinucleotide (NAD+).1828 NAD+ is a critical cofactor necessary for sirtuin activity. Alternate means of boosting NAD+ levels include taking a variety of NAD+ precursors,1829 as I’ll discuss in the Anti-Aging Eight section. Raising NAD+ levels is one of two basic approaches to sirtuin stimulation.1830 The other is via STACs, sirtuin-activating compounds, the most widely known of which is resveratrol,1831 a natural compound concentrated in the skin of grapes.

In vitro, apple extracts have been shown to activate sirtuins, as well as AMPK and autophagy, while suppressing mTOR signaling.1887 It’s perhaps unsurprising, then, that a meta-analysis of population studies found that those who ate more apples had a 15 percent lower risk of premature death.

A member of the ginger family, green cardamom (Elettaria cardamomum) is known as “the queen of spices.”1905 In a trial of patients with fatty liver disease, those randomized to a half teaspoon of cardamom three times a day with meals for three months not only had improvements in liver function and markers of systemic inflammation but they also saw a significant increase in sirtuin levels in their bloodstream.

As a bonus, the same cardamom dose over two to three months can significantly improve markers of inflammation and oxidative stress,1911 and be a safe, cheap, convenient way to decrease the level of triglycerides in the blood by about twenty points (mg/dL).

I enjoy it in my chai tea and like adding it to cocoa powder any time I’m chocolating anything up.

Sirtuins are a class of protein regulators that appear to play a key role in protecting us against a variety of age-related diseases, though their role in longevity is questionable.1920 Dependent on a molecule called NAD+, sirtuins can be upregulated by anything that increases NAD+ levels, including AMPK activation. Certain foods and supplements may also be able to activate sirtuins in other ways, but research on resveratrol has been largely disappointing and raised certain safety concerns.

snacking on apples and experimenting with adding cardamom to meals

At the tip of each chromosome is a protective cap called a telomere, which keeps our DNA from fraying or fusing with other chromosomes,

Remember the “Hayflick limit” from the Cellular Senescence chapter? Telomere shortening is the mechanism by which many cells are restricted from dividing more than about fifty times.1925 This cap on cellular immortality may limit our lifespan potential, but it may also protect us from tumor formation.

This may be another example of antagonistic pleiotropy.1927 What may have been helpful in letting us reach reproductive age so we could pass along our genes (not dying from a childhood cancer) may not bode well for successful aging and longevity (the littering of our tissues of zombified senescent cells from critical telomere shortening).

Thankfully, there’s a way not only to slow down the rate of telomere attrition but to build back up our shortest telomeres.

The answer lies in an enzyme found in Methuselah. That’s the name given to a bristlecone pine tree growing in California’s White Mountains. When it was named, the tree was the oldest recorded living being. Today, it’s nearing its 4,800th birthday. For context, Methuselah had already been alive for centuries before construction of the Egyptian pyramids had even begun. An enzyme found in the roots of bristlecone pines appears to peak a few thousand years into the trees’ lifespan and actually rebuilds telomeres.1957 Scientists named the enzyme telomerase. Once they knew what to look for, they found that the enzyme is present in our cells, too.

So, eventually, time may win out, but from one year to the next, we may be able to keep telomere shrinkage at bay, thanks to telomerase activation.

The main drivers of accelerated telomere loss may be oxidative stress and inflammation.

the subjects’ telomeres didn’t just shrink less or hold steady—they grew. Five years after that first intervention, their telomeres were even longer on average than when they had started participating in the study, suggesting for the first time ever that a healthy plant-based diet and lifestyle can boost telomerase enzyme activity and effectively reverse cellular aging.1995 But, was it the diet, the exercise, or the stress management?

So, as long as we’re eating the same diet, it may not matter how small our portions are, how much weight we lose, or how much we exercise; after a year, the subjects saw no benefit. In contrast, the individuals in the Ornish study on a whole food, plant-based diet who exercised only half as much and enjoyed the same amount of weight loss after just three months2016 appeared to acquire significant telomere protection.2017 In other words, neither the weight loss nor the exercise reversed cell aging by rebuilding telomeres. It was the food—and not just any diet.

even minor alcohol consumption during middle age might result in shortened telomeres,

The most pro-inflammatory food component is saturated fat.

The most anti-inflammatory food component is fiber.2045 The same representative sampling of thousands of U.S. adults found that the more fiber people consumed, the longer their telomeres tended to be.

about four cups2058 of green tea a day for five months experienced a significant boost in telomere length in the green tea group over placebo.

The study provided, for the first time, evidence that telomerase activity can respond in a matter of days to a food intervention. Not just any food, though, but the healthiest food out there—cruciferous, dark green leafy vegetables. Within sixteen days of stopping the kale, however, telomerase activity was back to baseline.2060 So, as I recommend in my Daily Dozen, try to fit cruciferous veggies into your regular dietary routine.

One of the reasons I don’t recommend taking green tea extract supplements is the risk of liver toxicity. We used to think such reactions were rare, on the order of one in a hundred thousand.

Excess sodium appears to be humanity’s number one dietary risk factor for death.