Longevity Science: Is It Based On Genetics?

The study of longevity, and the factors that contribute to it, has become a topic of increasing interest in recent years.

Advances in genetic research, as well as a deeper understanding of the impact of lifestyle and environmental factors, have led to new insights into how we can potentially extend our healthy lifespan.

This article delves into the scientific principles and interventions being developed to promote healthy aging. Whether you are a researcher, healthcare professional, or simply someone looking to improve their own health and wellness, this article offers a comprehensive and thought-provoking examination of the field of longevity.

What is longevity?

Longevity is a general term that refers to a person’s typical lifespan. While lifespan refers to the number of years you live, healthspan is a measure of the number of those years you spend in good health. For instance, a person may live to be 100 years old, and if the last 20 years are spent suffering from a chronic condition, the person’s healthspan would be 80 years.

Increasing population lifespan

Global population lifespan has been increasing over the last couple decades. For example, between 2000 and 2019, the global life expectancy has increased from 66.8 years to 73.4 years, an increase of nearly 7 years.

However, some scientists have predicted that with advances in biomedical technology, lifespan could increase up to 150 years old. Scientists and biotechnology companies focused on longevity and aging are currently working on extending human lifespans by slowing biological aging.

Chronological vs Biological age

Chronological age refers to the number of years a person has been alive, but is not always the best indicator of a person’s true age, and how healthy their aging is.

Biological age on the other hand is a measure that provides a more accurate assessment of how well a body is aging. Biological age tests take into account the cellular and tissue damage that the person’s body has accumulated over the years, based on lifestyle choices and genetics, to provide insight into how well the person’s body is functioning.

For example, a person who has lived a healthy life may have a chronological age of 30 years, but a biological age of 25 years. Scientists take different approaches to measure and study biological age, such as using biomarkers in the blood, and measuring epigenetic markers from the person’s cells.

What is longevity science?

Scientists study longevity with the goal of understanding the aging process to help find new ways of extending the healthy lifespan of the population.

Longevity researchers often focus on the underlying cellular and molecular causes of aging, called the nine hallmarks of aging. These include the shortening of telomeres and loss of stem cells with aging, and are thought to drive many of the physical changes that occur with age.

Attempting to slow aging with new treatments rather than treat individual diseases separately is different from how medicine is generally practiced today. However, the idea that more benefit will come from slowing aging over treating individual diseases is gaining traction and is known as the Geroscience hypothesis.

Longevity: Is it genetics or lifestyle?

Recent research suggests that healthy aging and longevity in humans may be influenced by a combination of both genetic and non-genetic factors.

Studies have found that around 75% of a person’s lifespan is determined by the lifestyle choices they make, such as diet, exercise and stress management. In addition, twin studies have estimated that genetics also play a role in longevity, accounting for approximately 25% of a person’s lifespan.

Longevity genes

By exploring the genetic basis of aging, researchers have identified several key genes and their variants that may explain why certain people live longer than others.

The term “longevity genes” refer to a set of genes whose functions include cellular maintenance and greatly contribute to a person’s longevity. These genes promote lifespan extension in different species, including worms, mice, and humans, and include:

• SIRT6: is a longevity gene involved in protein organization and DNA repair.
• APOE: provides instructions to produce a protein which combines with lipids to form lipoproteins responsible for controlling cholesterol and other fats.
• FOXO3: is involved in vital cellular mechanisms, such as energy metabolism, cell cycle regulation, and stem cell maintenance.

Genetics of centenarians

A centenarian is a person who has reached or surpassed the age of 100 years. This population of individuals has been the focus of numerous scientific studies in recent years, due to their unique life experiences, health outcomes, and overall longevity.

Although as we explained above, research into longevity has shown that lifestyle factors are the primary determinant of moderate longevity. But in the case of extreme longevity, such as in centenarians, genetics may be a more important factor. Some scientists have theorized that centenarians might have “perfect genomes”, meaning they may not possess the genetic susceptibility to age-related illnesses such as Alzheimer’s, cardiovascular disease, and cancer. These ‘super-agers’ also have protective genes that are thought to slow down aging and prevent age-related diseases.

Lifestyle factors

Lifestyle factors such as diet and exercise account for approximately three quarters of a person’s lifespan. This suggests that a person’s longevity is malleable, and that their daily choices may have a significant impact on their life expectancy.

In fact, a study conducted by Osaka University found that, even for those older than 80 years of age and for those with chronic conditions, incorporating five or more healthy habits, such as a regular sleep schedule and healthy food choices, into daily life could significantly increase remaining life expectancy.

Five of the most impactful lifestyle factors that determine a person’s longevity are discussed below:

Diet

The phrase “you are what you eat” very much applies when it comes to longevity. Studies from single-celled organisms, invertebrates, rodents, primates, and humans have revealed that diet plays a significant role in regulating the aging process and lifespan.

Several diets have been proposed as having longevity benefits, such as:

• The Valter Longo diet: the Valter Longo diet introduced by Dr. Valter Longo of the University of Southern California is predominantly vegan and low in calories. The 5-day intensive diet is said to mimic the longevity health benefits of fasting, such as increased autophagy, reduced cardiovascular risks, and diabetes. The diet has been shown to reduce markers of aging and age-related diseases.
• The Mediterranean diet, commonly consumed in Greece and Italy, is primarily plant-based with the exception of moderate fish consumption. The Greek variant of the diet contains olive oil and legumes as the staple of the diet. The diet has been associated with improved longevity primarily through reducing cardiovascular risk. Though, a study suggested the diet shows little to no protective benefits against cancer.
• Intermittent fasting is an eating pattern that involves a cycle of fasting and eating within a time period. Some research suggests longevity benefits of a 16:8 intermittent fasting schedule, in which you fast for 16 hours and eat within an 8-hour period per day. A study in mice has shown that long periods of fasting between meals helped male mice live longer and healthier lives, regardless of the content of their diets. In the blue zones region of Ikaria, about 150 days of religious fasting per year is commonly observed in this long-lived population.

Sleep

Sleep plays a vital role in the maintenance of regular homeostasis and promotion of longevity across different species, from rodents to humans.

Consistent and quality sleep is essential for cellular repair and immune function, and to help reinforce the strength of circadian rhythms.

Recent studies found that too much or too little sleep are associated with various aspects of aging and age-related diseases, such as:

• Increased chronic inflammation: sleep deprivation has been associated with increased expression of proinflammatory markers, which have been linked to aging and increased risk of disability, morbidity, and mortality. 
• Increased cellular senescence: cellular senescence is when the cell ages and permanently stops dividing but persists and releases damaging molecules. A study in mice showed that just one night of sleep deprivation can promote cellular senescence.
• Increased risk of all-cause mortality: an analysis of 95,259 individuals showed an association between sleep duration and all-cause mortality.

Exercise

Regular exercise and physical activity are associated with longevity health benefits, such as reduced cellular senescence and promoted mitochondrial health.

In fact, a study revealed that any form of regular physical activity can increase life expectancy by 0.4 to 4.2 years with regular physical activity, and decrease all-cause mortality by about 30% to 35%.

Certain exercise protocols have been suggested to promote longevity, and include:

• Strength training: numerous studies have associated strength training with increased longevity and healthier aging. One study suggested that 30-90 minutes per week of strength-training reduced the risk of early death from all causes by 10-20%.
• HIIT training: high intensity interval training, or HIIT workouts involve cycles of short intense and explosive exercises alternating with brief recovery periods. HIIT has been shown to improve VO2 max, which is a measure of the maximum amount of oxygen your body can use during exercise, and is a strong predictor of longevity.

Tobacco smoking

Tobacco smoking is one of the main contributors to cancer and cardiovascular diseases, and can greatly accelerate the aging process of organs and significantly shorten lifespan.

Life expectancy for smokers is at least 10 years shorter than for nonsmokers. In addition, quitting smoking is the only intervention that has been shown to reverse biological age according to a standard biological age test.

A genome-wide study on the organs of non-smokers, smokers, and ex-smokers found that smoking increased the epigenetic age of airway cells and lung tissue by 4.9 and 4.3 years, respectively.

While tobacco use may have some health benefits, such as lowering risks of thyroid cancer in men and possessing protective effects against hypertensive disorders, the benefits do not seem to outweigh the costs when it comes to lifespan.

Alcohol consumption

Excessive alcohol consumption is commonly associated with increased risk of mortality and the development of several diseases, such as liver disease and many types of cancer.

Some studies have suggested that modest to moderate alcohol use may actually promote longevity. One study demonstrated that modest drinkers (<1 drink per day) on average showed a gain of nearly 1 year in life expectancy. That said, other research has suggested that the longevity benefits in modest drinkers are likely to be due to other factors, and not alcohol consumption.

Red wine, a beverage commonly consumed as a part of the Mediterranean diet, has been suggested to promote longevity. The resveratrol compound found in red wine has been shown to extend lifespan in yeast by 70%, and in animal species including worms, fruit flies, and vertebrate fish. However, the amount of resveratrol in red wine is low, and recent evidence suggests that resveratrol does not offer longevity benefits.

Other studies have given us reasons to believe that alcohol consumption in any amount influences telomere shortening, resulting in lifespan reduction.

[Read more: Sneaky Spirits: An Unbiased Look at Alcohol’s Effect on Longevity]

New longevity interventions

Although there are simple lifestyle changes that one can make to influence their longevity such as the five explained above, researchers are also investigating new biomedical technologies and drugs to extend healthy lifespan. Two of the most promising drugs that have been suggested to promote longevity include:

• Rapamycin: is an FDA-approved drug used to suppress the immune system during organ transplants. Research has shown rapamycin to extend healthy lifespan in worms, yeast, flies, and mice which led scientists to suggest it could slow down aging in humans, becoming one of the first “anti-aging drugs”. The PEARL clinical study is exploring the potential of rapamycin as an anti-aging drug in humans. It is anticipated that preliminary results from the study will be available in 2023.
  
• Metformin: is an affordable, widely-prescribed diabetic medication that has been found to increase healthy lifespan in worms, mice, and rats. Currently the Targeting Aging with Metformin (TAME) trial is investigating whether metformin can be used to prevent the onset of age-related conditions such as heart disease, cancer, and dementia.

Conclusion

Genetics and lifestyle both play a role in determining a person’s lifespan and healthspan. However, given that up to 75% of lifespan is determined by lifestyle factors, individuals interested in extending their lifespan may benefit from changing how they live their lives.

Lifestyle factors such as diet, exercise, smoking status and alcohol consumption have been demonstrated to influence longevity. By making incremental changes, individuals may be able to slow the rate of their aging and live longer and healthier lives.

You can also explore: Longevity 101: The Ultimate Guide To Increasing Your Healthspan & Lifespan