What is Longevity?
People have been on a quest to live longer since the dawn of times. Could it possibly be here?
First, we need to define longevity. Classically, longevity defined as a long duration of individual life. However, Dr. Sinclair’s definition is living longer AND HEALTHIER life.
Improving health is main goal of current longevity movement. Disease is the main barrier to reaching maximum lifespan or having good quality of life at older age. Most common diseases that attributed to older age are Alzheimer’s disease, cancer, Parkinson's, Rheumatoid Arthritis, and many others.
Luckily, longevity can be influence by many factors (sex, genetics, diet, exercise, etc). For many years, genetics were considered non-modifiable (fixed) factor. However, we are learning that genetics can be altered.
First, it’s important to understand how genetics and aging related. Every cell in our body has a set of instructions (genome) that tells is when to grow, what proteins to make, and many others. As we age, this genome is damaged. Dr. Sinclair like to describe it as scratches on the surface of CD. That damage is leading to cell not working properly, as a result you can see diseases such as cancer, frailty, diabetes, cardiovascular problems.
What regulates longevity?
According to Dr. Sinclair there 3 main ways to increase longevity: mTOR, AMPK, and Sirtuins pathways.
mTOR or mammalian target of rapamycin is a protein that regulates different cell processes and plays role in protein recycling. It measures three essential amino acids and gives commands. It can either tell cells to grow in the state of abundance or to to recycle (autophagy) in amino acid levels are low. Decreased mTOR activity has been found to prolong lifespan in studies on bacteria and mice.
AMPK or AMP-activated protein kinase is an enzyme that plays role in energy metabolism. It is heavily affected by glucose levels. Activation of AMPK has shown to prolong lifespan in studies on bacteria.
Sirtuins are the group of proteins that regulate aging, transcription, inflammation, and energy use. There are seven sirtuins in humans. Three of those are in the inner part of the cell (nucleus), where they control DNA repair and genome packaging.
How to activate longevity pathways?
1. Fasting.
As we saw above, most of these pathways affected by presence of nutrients in the body: mTOR is activated by presence of amino acids, AMPK is inhibited by high glucose levels, and sirtuins activated by fasting.
Dr. Sinclair recommends intermittent fasting as most convenient one. These are the four most common types of intermittent fasting:
Time-restricted eating. Feeding is allowed for certain period during the day and the rest is reserved for fasting.
The twice-a-week method. You eat as usual during the week and reserve two nonconsecutive days for low caloric intake (<500 calories).
Alternate day fasting. Alternating between fasting and non-fasting days.
The 24-hour fast. Complete caloric abstinence for 24 hours. Usually done once or twice a week.
Caution: Intermittent fasting is not safe for some people and should not be treated lightly. People who are pregnant, children, people at risk for hypoglycemia, people with certain chronic diseases, or people with eating disorders should avoid fasting. Contact your healthcare provider before attempting any type of fasting.
2. Diet.
Dr. Sinclair is a proponent of vegetarian diet. He believes that avoidance of animal proteins (i.e. meat) can lead to mTOR and sirtuin activation. High levels of three essential amino acids leucine, isoleucine, valine decrease mTOR activity, which leads to accumulation of old and malfunctioning proteins.
He also highlights harmful effects of high glucose and fructose diet. Glucose can attach to proteins leading to their malfunction. In addition, AMPK and sirtuin are “sensing” glucose and will be switched off by high sugar levels.
As a result, high levels of glucose can decrease longevity, lead to type 2 diabetes, and cardiovascular disease. By keeping glucose levels low and consistent, you can prevent brain fog, decrease protein “caramelization” (protein glycation), stimulate body’s defense systems (AMPK, sirtuins).
Dr. Sinclair rates different diets based on hazard ratio (likelihood) of mortality as follows:
Diet | Hazard ratio | Meaning |
Non-vegetarian | 1 | no mortality reduction or highest risk of mortality |
Semi-vegetarian | 0.92 | 8% reduction in mortality rates |
Lacto-ovo | 0.91 | 9% reduction in mortality rates |
Vegan | 0.85 | 15% reduction in mortality rates |
Pesco-vegetarian | 0.81 | 19% reduction in mortality rates |
3. Exercise.
Dr. Sinclair is a big proponent of exercising too. He highlights such benefits as preventing muscle atrophy, maintaining normal hormone levels (particularly testosterone), maintaining bone health.
Exercises also protect the body from the diseases by preventing many forms of cancer, cardiovascular diseases, all cause mortality.
He recommends exercises that induce hypoxic state: walking, running, cycling. These aerobic activities stimulate manufacturing of mitochondria (small power plants in our cells), building of more blood vessels to ensure adequate blood supply throughout the body.
The studies show that exercising can dramatically decrease amounts senescent cell (zombie cells) in the body, effectively reversing aging process.
4. Supplements.
Supplements can give your body additional boost beyond what modern foods can provide. Dr. Sinclair studies NAD boosters in his Harvard lab.
Here are most common supplements that can be used for longevity:
Nicotinamide Mononucleotide (NMN)
Nicotinamide Riboside (NR)
Resveratrol
Fisetin and Quercitine
Berberidine
Each supplement has it’s own benefits and activates different longevity pathways. Some of the common benefits include: increase in NAD+ levels, increase in insulin sensitivity, increase in mitochondrial function, and slowing down aging. Supplements are is a big topic for discussion. In our future blog posts we will dive into specific details of each one.
4. Cold therapy.
When we talk about cold, we have to bring up brown fat. Initially brown fat was discovered in babies which helps to protect them from cold. In adults, brown fat is found in small amounts in shoulder blade area. However, brown fat production can be stimulated by exposure to cold.
There are several ways to stimulate your body. Most popular is intense cryotherapy. You can also try cold water plunges, cold shower, or sleep without a blanket to lower your core temperature. The benefits of brown fat include increase in metabolic rate, burning unhealthy white fat, decrease on free radical production production of signaling molecules that believed to play role in diabetes and cardiovascular disease prevention. More research is underway.
4. Heat application.
On the opposite side we have emerging research about benefits of heat. Sauna practice is very popular in Finland and neighboring Scandinavian countries. Several studies found decrease of up to 20% in cardiovascular disease and mortality caused by heart attacks for people who frequent saunas several times per week.
Exposure to intense heat is believed to activate heat shock proteins (HSP). HSPs play role in correct proteins folding, which improves function of the cells; building new blood vessels; and production of more mitochondria. There are a variety of different saunas: traditional or steam sauna, dry heat sauna, steam bath, infrared therapy sauna. If you opt for infrared sauna there could be additional benefits such as reversal of skin aging and improved hair growth.
In conclusion, our bodies developed complex ways to stave off adversity. By exploring our body's natural defense mechanisms we can live longer and healthier lives. Each of these topics deserves deeper dive. We look forward to explore them with you.
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https://www.cell.com/cell-metabolism/fulltext/S1550-4131(12)00192-1
https://www.cell.com/cell-metabolism/pdf/S1550-4131(14)00265-4.pdf
https://www.sciencedirect.com/science/article/abs/pii/S0047637409001523
https://www.nia.nih.gov/news/longer-daily-fasting-times-improve-health-and-longevity-mice
https://www.nih.gov/news-events/nih-research-matters/fasting-increases-health-lifespan-male-mice
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