The Science of Healthy Aging
As we get older, the dream of sustaining good health for as long as possible is increasingly top of mind. Aging is a continual process, and right now, different scientific fields are working together to not only find a novel approach to increase lifespan but also to maximize the time we as humans spend disease-free. Reducing the length of time spent sick is associated with the new term: ‘Compression of morbidity’.
Scientists in the field of aging say that it is not a question of “if”, but “when”, that the tools to reprogram cells, slow aging, and in some cases even reverse it, are available to be used on humans.
Until then, we can experiment with changing habits a little bit at a time, which is simple (in most cases), free, and harmless. We will go through the concept of intermittent fasting below, and as always, remember to speak with your healthcare team if you have difficulty controlling diabetes, are pregnant, or have any other chronic issues.
Aging is commonly characterized by an increasing loss of bodily integrity leading to impaired mental and physical functions as well as increased vulnerability of death. Aging is also related to isolation - the absence of social relations. If you are curious to know more about aging, this paper reviews the eight to nine common denominators of mammalian aging.
We briefly brought up the concept of ‘hormesis’ in a previous blog post where we discussed lectins. To simplify this concept, it can be described as: “What doesn’t kill you, makes you stronger”.
Fasting, exercising, being cold or hot, eating a variety of plants containing phytonutrients, and eating low protein diets are all stressors to our body and examples of hormesis - something that is generally good for us in optimal levels or doses, and that will not cause long-term damage.
Many of these known healthy stressors to our body are actually explored in the ‘longevity’ field these days, with the hope to maximize our healthy lifespan (i.e. healthspan) by activating our longevity defense genes. An example of this is the mammalian sirtuin family of genes (1-7). The sirtuin family mediates processes involved with caloric restriction through NAD+, and the family of genes is originally described as regulators of longevity, apoptosis, and DNA repair systems.
Hormesis-mimicking supplements for humans are also being researched, like metformin, found and originally developed from the plant goat’s rue (also known as lilac), the compound resveratrol, often extracted from the skin of ‘stressed’ grapes, and NAD! boosters like NMN and NR. If interested to know more about these three ‘stressors’, we have added a few notes to each in the end.
It is generally recognized that reducing food availability over a lifetime, also known as caloric restriction, has remarkable effects on aging and the life span in mice and non-human primates. Intermittent fasting may modify a wide range of chronic disorders such as obesity, diabetes, cardiovascular disease, cancers, and neurodegenerative brain diseases.
Therefore, when you eat, not what you eat, has recently gained a lot of popularity. In addition, finding the optimal diet that works for everyone is rather impossible. Fasting is, on the other hand, something that is more or less simple and easy to integrate with most lifestyles - giving our body a well-needed rest.
Most people have three meals a day including snacks, so intermittent fasting usually doesn’t occur. In addition, as far as we know, there has never been a selective pressure for snacking, which may turn into ‘grazing’, throughout the day. In comparison to grazing, snacking is often a planned behavior, not emotional, to keep you from overeating at the main meals. Sometimes, we can overdo it by overeating what our body needs, which can lead to weight gain and other health issues. Speak with your dietitian or healthcare provider to determine how many calories your body needs to meet your energy needs.
Cellular responses to intermittent fasting are different from what’s happening in the cells following a meal, the postprandial phase. Intermittent fasting induces evolutionary adaptive cellular responses that improve glucose regulation and increases your body’s resistance to stress and inflammation. This is because your cells activate different pathways during fasting, you can say that they adopt a stress-resistance mode through reduction in insulin signaling, as well as remove and repair damaged molecules. Intermittent fasting has also for a while now been used as a promising dietary intervention for alleviating T2D symptoms. In the fed state, cells will focus on specific processes of growth and plasticity.
If you find the potential benefits of fasting interesting, it is important to keep in mind that there are different forms of intermittent fasting. Below, we have selected three different methods for mealtime schedules:
- Alternate day fasting (i.e. you fast every other day, eating around 500-700 calories on fasting days. Typically, people start out at higher amounts of calories on fasting days until they become acclimated and slowly, over time, decrease to the goal of about 500-700 calories on fasting days)
- 5:2 intermittent fasting (i.e. reduce caloric intake two days per week, the other five days you eat normally)
- Daily time-restricted feeding (choose for example to fast between 12 to 16 hours per day)
Time-restricted feeding is for many the easiest form of fasting to integrate with lifestyle. You choose the window of fasting and fed state according to your daily rhythm. For example, if you are not a late-night snacker, eat early dinner around 6 pm (this is easy if you are a parent with small children), and do not eat again until breakfast the next day. If you eat breakfast at 7 am, your fasting window is 12 hours. If you wait until lunch, your fasting window will be between 16 to 18 hours.
I find time-restricted feeding easy, as I can do it overnight, and because I do not mind skipping breakfast or even lunch. Dinner is for me the most important and most interesting meal of the day, and I do like to snack in the evening. Therefore, I typically don’t eat breakfast to get a fasting window of at least 12 hours. Black coffee or tea in the morning (without milk and sugar) is fine to have and will not break your fasting window.
Weight loss often accompanies fasting, but many studies on fasting show that it is the metabolic switching, from the use of glucose as fuel toward the use of adipose cell-derived fatty acids and ketones, that is mostly behind the benefits of fasting, influencing health and aging.
Read here, if interested in knowing more about Intermittent Fasting on Health, Aging, and Disease.
Intermittent fasting and the human gut microbiome
Long-term adaptations of fasting combined with physical activity have shown to increase disease resistance and mental performance through a healthier gut microbiota among others.
A pilot study in humans on intermittent fasting showed an increase in Akkermansia muciniphila and B. fragilis group, which are considered healthy gut microbiota members. A. muciniphila strain is also part of the novel strain formulation in the ‘Pendulum Glucose Control’ product. This is considered an interesting preliminary finding of fasting and gut microbiota interactions.
Moreover, it may be speculated that without available nutrients from the diet in the fasting periods, bacteria like A. muciniphila that can metabolize and regulate mucin o-glycans in the mucin layer covering our GI tract may have a superior advantage over other bacteria species.
As the gut microbiota contributes and induces immune responses in the body, supplementing specific probiotics to the elderly has long been proposed as an anti-immunosenescence treatment. A. muciniphila has also been found here to be capable of rejuvenating the aging immune system because of its unique functions and regulations within gut integrity. However, more is yet to be understood about age-related imbalance in the gut microbiome.
The NAD+ boosters, NMN and NR, have shown to be efficacious in cell cultures and to benefit healthy aging in mouse models. No negative effects have been observed in long-term mouse studies. Only small scale clinical trials have been conducted with humans to date.
Resveratrol is a polyphenol found in plants, especially in stressed plants as part of their defense strategy against predators or unfavorable conditions (drought, sunlight, nutrient restriction). It is often extracted from grape skins, this is why red wine is considered a source of resveratrol. Especially Malbec and Pinot Noir grapes, which are very stress-sensitive, contain the highest concentrations. As a tip, you can also look for wines like Dry Farm Wines, naturally fermented wines, or even Stressed Vines, which should have some of the highest levels of polyphenols like resveratrol.
Resveratrol has been shown to enhance and activate sirtuin 1, which promotes adaptations related to metabolic homeostasis. Dietary supplementation with resveratrol is therefore thought to have beneficial effects on diseases of aging - for example, it may increase insulin sensitivity through the metabolic regulator, AMPK.
Resveratrol is partly metabolized by our gut microbiota. The therapeutic potential of this compound may therefore also be due to interactions with our gut bacteria, like changes in bacterial compositions associated with beneficial metabolic events.
Scientists are working to validate metformin as an anti-aging medication - metformin’s ability to compress morbidity has been demonstrated pre-clinically, and the hope is to demonstrate the same in humans.
It is widely used now in diabetes treatment but has also been shown to increase the production of longevity-promoting molecules in our cells. Metformin is a good example of a drug that is relatively safe and cheap with potentially big benefits in the field of increasing healthy lifespan. However, Metformin is currently not indicated for aging as further research needs to be conducted. In addition to diabetes, metformin has also been found to have positive results in treating cancer and cardiovascular diseases.