Sirtuins and Healthy Aging: What These Little-Known Enzymes Do for Your Body

So what are sirtuins?

Sirtuins, or sirtuin proteins, are enzymes that regulate numerous cellular functions, including aging, inflammation, detoxification, stress resistance, fat and glucose metabolism, circadian rhythms, and mitochondrial biogenesis.

In humans and other mammals there are seven different sirtuins (SIRT-1 through SIRT-7) that are involved with different functions – and are either directly or indirectly related to longevity.

It’s likely you know about the research that shows that restricting calorie intake can slow the aging process. This is in part true because calorie restriction stimulates sirtuin activity – the discovery that started all the buzz about sirtuins.

Sirtuin research started at MIT in 1991, when the first sirtuin discovered was in the yeast species Saccharomyces cerevisiae (commonly known as baker’s yeast). It was named Sir2 (for “Silent Information Regulator”).

Sir2 research in yeast found:

1. Inhibiting Sir2 resulted in shortened lifespan,
2. Increasing Sir2 lengthened lifespan,
3. Sir2 levels decreased with aging, and
4. Sir2 appeared to affect aging, in part, through having positive effects on telomere length – a factor that seems to be related to longevity.
   
   

What do sirtuins do in the body?

Sirtuins appear to have regulatory effects in most systems of the body – brain and nerves, metabolism, heart and blood vessels, and immune system, to name just a few. Understanding the role of sirtuins in aging starts with knowing what each one of the seven sirtuin proteins actually does. Here is what some of these studies have shown.

SIRT-1 is the human counterpart to Sir2 in yeast – the sirtuin that has been most studied for longevity. It’s the sirtuin that is up-regulated by calorie restriction, which is known to slow the aging process. Up-regulating SIRT-1 has also shown benefit for neurological support.

SIRT-2 may help maintain a healthy weight, with decreased levels seen in the fat tissue of obese individuals, while increased levels are seen in animals subjected to calorie restriction.

SIRT-3 exerts potent antioxidant activity; in animal studies, those with low levels of SIRT-3 experienced high levels of oxidative damage from free radicals.

SIRT-1, -2, and -3 support healthy metabolic activity, providing benefit for weight-related health issues such as metabolic syndrome. One or more of these three sirtuins has the following beneficial effects in the body:

• Slows glucose production in the liver in cases of obesity
• Prevents accumulation of fat in the liver
• Inhibits adipogenesis (fat formation)
• Supports production of healthy HDL cholesterol
• Supports insulin release from the pancreas
• Enhances the health of the beta cells in the pancreas that secrete insulin
• Increases adiponectin that supports a healthy inflammatory response in fat cells
• Improves insulin sensitivity in muscles – meaning muscles are able to take up glucose from the bloodstream more efficiently
• Enhances formation of new mitochondria in muscle cells

SIRT-4 regulates insulin sensitivity. Telomeres are the end caps on chromosomes that help prevent the chromosomes from deteriorating. These end caps tend to shorten with age. Some preliminary research indicates SIRT-4 might have a positive effect on preserving telomere length.

SIRT-5 plays a role in liver detoxification by regulating the step of converting ammonia to urea for excretion from the body.

SIRT-6 may be the most important sirtuin for longevity, although research is very preliminary. In animals missing or severely deficient in SIRT-6, dramatic aging occurs in the first weeks of life, including immune deficiency, bone degeneration, and colitis.

SIRT-7 may also play a role in longevity: Lack of SIRT-7 in mice results in significant premature aging, characterized by an enlarged heart.

What can you do to positively affect sirtuins?

Several natural substances, including nutrients, botanical extracts, and hormones, can positively support sirtuin activity. For those exploring sirtuins and aging, here’s what the current research shows about both lifestyle habits and sirtuins supplements.

Resveratrol, a compound in red wine, is the most well-known and researched of the natural sirtuin enhancers and is often part of every discussion about which dietary supplements promote healthy aging. Like calorie restriction, resveratrol stimulates SIRT-1 expression, a key way it supports health during the aging process.

Resveratrol’s effect of up-regulating SIRT-1 results in antioxidant effects and balances inflammatory chemicals, resulting in improvements in insulin resistance and support for the nervous and muscular systems.

In a test tube study, resveratrol increased SIRT-4 with a positive effect on preserving telomerase – the enzyme that protects telomeres.10 Whether this same effect occurs in humans remains to be studied.

Sirtuins are NAD-dependent – they can’t function without it. And nicotinamide riboside (NR) increases NAD+ levels.

Building on this study, researchers at the University of California Davis found that calorie restriction support for lifespan and stress resistance in this yeast model were dependent on adequate amounts of NR.

Pterostilbene, a compound found in high amounts in blueberries, is structurally similar to resveratrol and has some of the same effects, including stimulating SIRT-1 activity with subsequent antioxidant capacity and beneficial effects on inflammation. Pterostilbene has been shown to protect the cells of the heart from oxygen deprivation by up-regulating SIRT-1.

Curcumin, a flavonoid from turmeric, possibly exerts some of its myriad positive benefits by supporting sirtuin expression. In a test tube study, curcumin protected nerve cells from damage by up-regulating SIRT-1 and exerting antioxidant effects. Overall, curcumin has been shown to up-regulate a number of sirtuins, including SIRT-1, -3, -5, -6, and -7.

Melatonin also possibly exerts some of its beneficial effects via sirtuin activation. Melatonin has been shown to protect the brain from the effects of aging by up-regulating SIRT-1.

Does exercise promote sirtuin levels?

Because regular physical exercise exerts a positive impact on health in many ways, it should come as no surprise that it has been shown to have a positive effect on sirtuin levels. Mildly intense physical activity induces SIRT-1 activity. In human skeletal muscle of younger and older adults, exercise increased SIRT-1 and inhibited age-related sarcopenia (muscle wasting), nerve degeneration, and free radical damage.

Sirtuins, aging, and the future of longevity

There is still much we don’t know about sirtuins and how they work in the body. And it’s not all black and white – as with anything, it’s a matter of balance. While encouraging sirtuin activation in one situation may provide benefit, in another situation, benefit might come from inhibiting it. And many of the substances that support healthy sirtuin balance also exert their benefits in other ways. As with most research in its infancy, the possibilities are endless.