Calorie restriction is a bit of a magic bullet for longevity that can be difficult in practice. Science has shown, however, that reducing calories extends lifespan because of its connection to an increased level of sirtuins – a family of signaling proteins that are critically involved in metabolic regulation.
Sirtuins are central to the calorie restriction benefits experienced in skeletal and cardiac muscle, which become damaged by age and disease over time.
There are seven sirtuin family members (SIRT1-7) in mammals, including humans. Sirtuins operate in different parts of a cell: nuclear (SIRT1, SIRT6, and SIRT7), mitochondrial (SIRT3, SIRT4, and SIRT5), and cytosolic (SIRT2) forms.
Some sirtuins are found in more than one area.
SIRT1 operates in the nucleus. It “controls both glucose and lipid metabolism in the liver, promotes fat mobilization and stimulates brown remodeling of the white fat in white adipose tissue, controls insulin secretion in the pancreas, senses nutrient availability in the hypothalamus, influences obesity-induced inflammation in macrophages, and modulates the activity of circadian clock in metabolic tissues.”
SIRT4 operates in mitochondria. Known as a longevity regulator, SIRT4 is considered a mitochondrial-localized tumor suppressor. In a 2018 study in fruit flies, flies modified to make extra SIRT4 saw their healthy lifespans extended by 20%. Boosting SIRT4 in humans may effectively boost age-related metabolic decline and disorders, including diabetes and obesity.
SIRT6 works in the nucleus and plays multiple roles in metabolism, aging, and disease, including DNA repair. SIRT6 deficiency induces chronic inflammation, autophagy disorder, and telomere instability. Over time, these conditions can result in cardiovascular diseases. For this reason, SIRT6 plays a crucial role in protecting against cardiovascular disease.
What Are Sirtuin Activators?
Sirtuins regulate physiological responses to metabolism and stress, two essential factors in aging.
Sirtuin activators, or sirtuin-activating compounds (STAC), are chemical compounds that influence sirtuins.
STACs can be either naturally occurring or synthetic. Resveratrol (3,5,4′-trihydroxystilbene), for example, is a naturally occurring antioxidant found in grapes. Resveratrol was found to activate SIRT1 more than 10-fold. Later, this naturally occurring STAC was synthesized to have lower toxicity and higher potency and impact on SIRT1.
Intermittent Fasting and Sirtuins
Fasting has been shown to produce benefits that protect mice (and their cells) from harmful metabolic conditions and decrease the incidence of carcinogenesis. Fasting may also slow tumor growth and boost the performance of chemotherapy drugs in various cancers.
The mechanism that produces these benefits is partly attributed to the metabolic regulation by the sirtuin family proteins. Fasting specifically activates SIRT1 and SIRT3.
As the link between the fasting process and the role of sirtuins becomes better understood, a new metabolic diagram of cancer prevention or treatment is possible.
Foods with Sirtuin Activators
Polyphenols are antioxidants found in food that activate sirtuins and guard against cancers and cardiovascular disease.
Resveratrol – another sirtuin activator that is found in grapes, grapes, berries, red wine, and other foods – produces anti-platelet, anti-inflammatory, anti-cancer, and anti-mutagenic effects, as well as protection from atherosclerotic disease.
Other sirtuin activators include Butein and Fisetin. Butein is found in the stems of Rhus verniciflua stokes and produces anti-inflammatory, blood pressure lowering, and anti-cancer effects. Fisetin, found in strawberries and other fruits and vegetables, can enhance long-term memory.
The sirtfoods encouraged by the diet include arugula, buckwheat, capers, celery, cocoa, coffee, extra-virgin olive oil, matcha, kale, red wine, strawberries, turmeric, and walnuts.