How About the Good Old Apple?

Resveratrol is probably the best-known STAC, but thousands more have been discovered. In vitro, apple extracts activated sirtuins as well as AMPK and autophagy, while suppressing mTOR signaling. It is only logical, then, that a meta-analysis of population studies found that people who ate more apples had a 15 percent lower risk of early death. But how many apples is “more”? The “high” apple-consumption category meant an average of a quarter of an apple a day. A study looking at the highest apple consumption—half an apple a day compared to less than one apple a month—found a 35 percent lower risk of dying early. That could translate into roughly four more years of life. Forget the doctor. An apple a day might keep the undertaker away.

Only one phytonutrient from apples, phlorizin, promotes sirtuin expression and extends the lifespan of yeast, though it also increases levels of the antioxidant enzyme superoxide dismutase, so it is not clear what role the sirtuin played. At least in fruit flies, the increase in average lifespan from an apple extract requires intact antioxidant enzymes, suggesting it is more of an antioxidant effect. Even simple apple fiber (pectin) had a life-extending effect, and it wasn’t just due to calorie dilution (more food volume from fiber). The pectin group actually ate more and still lived longer. But the whole apple may be better than the sum of its parts.

When apple flesh was added to a prematurely aging mutant yeast that normally only lives ten days, it lived eleven days; with apple peels, up to 14 days. Looks like the best stuff is in the peel, right? What do you think happens if you add both flesh and peel? I would have assumed the whole apple would increase lifespan to 11 to 14 days, since the peel components would be diluted, but I would have been wrong. The whole apple led to more than a doubling of lifespan, increasing it to 21 days.

Something similar was seen in C. elegans, where extracts from whole apples extended average lifespan by up to 39 percent, more than three times as much as the 12 percent achieved by the subfraction of purified apple components (though the studies also used different apple varieties, Red Delicious versus Fuji). At least in C. elegans, the sirtuin dependence of the longevity effect was confirmed.

If components from apple peel and flesh show synergy and do more together than separately, couldn’t you also combine apples and blueberries? In C. elegans, both apple and blueberry extracts extended life, but mixed in equal parts, they extended life considerably more than either component alone. Such findings reinforce the common-sense insight that we should get our nutrients as much as possible from many whole foods rather than from single-ingredient pills.

The Queen of Spices

Are there more “sirtfoods,” foods that activate sirtuin? Many foods increase cellular sirtuin activity in a Petri dish, but very few have been tested in humans. 200 micrograms of selenium daily, given for ten weeks, can increase sirtuin expression, but as I note in see.nf/nacse, this dose has been found to raise diabetes risk with long-term use. Curcumin, the pigment that makes turmeric yellow, works in vitro and in animal models but fails to significantly change sirtuin gene expression in humans, even when taking the equivalent of a quarter cup of turmeric daily for months. But one spice that might work is cardamom.

A member of the ginger family, green cardamom (Elettaria cardamomum) is known as the “queen of spices.” In a study of patients with fatty liver, those randomized to take three half-teaspoons of cardamom daily with meals, for three months, not only saw improvements in liver function and systemic inflammation markers, but their sirtuin levels in the blood also rose significantly. Now, the thing is, we are not entirely sure about the source or significance of sirtuins in the blood. It doesn’t behave like a hormone. Each cell seems to make and use its own sirtuins internally. But blood levels decline with age, and accelerated sirtuin decline is associated with age-related conditions like frailty, cognitive decline, and Alzheimer’s, suggesting sirtuin might be a biomarker of aging.

As an added benefit, the same cardamom dose, given over two to three months, significantly improves markers of inflammation and oxidative stress and is a safe, inexpensive, and practical way to lower blood triglyceride levels by about 20 points (in mg/dl). I enjoy cardamom in chai tea and like adding it to cocoa powder whenever I make something chocolaty. So far, no significant side effects are known from taking such doses, but long-term data are not yet available.

AGEs Suppress Sirtuins

Should we avoid anything in particular if we want to preserve sirtuin function? Smokers have reduced sirtuin levels in their lungs, and in vitro, cigarette smoke extracts actively decrease both the amount and activity of sirtuin in lung cells, allowing cause and effect to be determined. Advanced glycation end-products (AGEs) in smoke could contribute, since AGEs suppress sirtuin expression in vitro, and feeding mice AGEs induces sirtuin deficiency in the brain, along with impairment of learning and memory performance. Unfortunately, as we learned in the chapter on glycation, people also take in AGEs through food.

It increasingly appears that sirtuin activity plays an important role in protection against Alzheimer’s dementia. The fact that dietary AGE intake is linked to lower sirtuin expression shows why a high AGE burden in blood, brain, and diet is associated with cognitive decline in older adults. Researchers concluded that sirtuin deficiency in humans is “both preventable and reversible by reducing AGEs,” and they suggested that avoiding high-AGE foods could be a new strategy in the fight against the Alzheimer’s epidemic. However, it is unlikely that AGEs in food play a central role in sirtuin regulation, because a cross-sectional comparison among healthy omnivores, vegetarians, and vegans found no differences in sirtuin expression or activity.

Food for Thought

Sirtuins are a group of protein regulators that appear to play a key role in protecting us from a range of age-related diseases, though their role in life expectancy is questionable. Because they depend on a molecule called NAD+, sirtuins can be upregulated by anything that raises NAD+ levels, including activation of AMPK. Certain foods and supplements can activate sirtuins in other ways, but the research on resveratrol has been largely disappointing and has raised some safety questions.

To help slow down this pathway of aging, you should daily: