Intracellular biochemical pathways to longevity

By Katherine Shagoury

We’re all going to grow old, and there’s nothing we can do about that, said Robert Rountree, MD, at the 2019 Integrative Healthcare Symposium in New York City. But there are ways that we can change the course of that condition.

The maximum human life span is 122 years, with the most recent average life expectancy in the U.S. at 78 years. According to the United Nation’s Population Division, the median age will increase from 26 to 36 by the year 2050, and the number of people older than 60 will triple.

With increasing aging populations comes many challenges, Rountree said. If more people are living past their 100^th birthdays, the key question, he says, is will these people be living well or just living longer?

A pessimist might say an increase in average lifespan will be accompanied by an increased burden of age-associated diseases. Physical dysfunction and incapacity to respond to stresses become more prevalent toward the end of life, Rountree said.

However, Rountree said he prefers an optimist’s view—physiological and psychological markers of aging are modifiable with a few primary prevention measures, such as stopping smoking, reducing body mass index (BMI) and regular exercise. These measures, Rountree said, can reduce lifetime disability.

A major question is whether interventions can be created that enhance lifespan as well as increase lifespan, Rountree said. How can we help people age well?

This opens the door to treating aging as a disease, Rountree said. There are four key physiological pathways associating with accelerating aging:

1. Telomere attrition
2. Oxidative stress
3. NFKB or “Inflammaging”
4. mTOR

As we age and cells divide over time, telomeres shorten and eventually cell division stops, said Rountree. Several risk factors contribute to this aging process:

• Chronic stress, anxiety, or depression
• Chronic insomnia or sleep deprivation
• Lack of social support from family and friends
• Sedentary lifestyle
• Processed foods and sweetened beverages
• Oxidative stress from cigarette smoke, air pollution, etc.
• Chronic toxin exposure from pesticides and other chemical toxins

But how do we address this? Rountree offers several factors associated with longer telomeres, which include:

• Regular exercise
• Good social support
• Meditation
• Low stress  
• Good quality sleep
• Omega-3 fatty acids
• Multivitamins
• Vitamin D
• Green tea

Free radicals damage also plays a major role in aging, Rountree said. However, this is fairly simple to address with exercise. Exercise-induced oxidative stress ameliorates insulin resistance, he said, and causes an adaptive response promoting endogenous antioxidant defense capacity. Supplementation with antioxidants may preclude these health-promoting effects, Rountree said.

 Inflammation may predict successful aging more so than telomere length, Rountree said. The key, he said, is to reduce consumption of inflammatory foods, including processed sugars and carbohydrates and fast food. Foods like turmeric can calm inflammation and stimulate circulation, Rountree said.

Lastly, Mechanistic Target of Rapamycin (mTOR), a major nutrient sensor that regulates cellular growth, development, proliferation, metabolism. Studies are showing aging and age-related disease are a result of chronic mTOR upregulation, which signals for growth and development, even when it’s not needed, Rountree said. This can lead to cancer, obesity, neurodegenerative diseases, and autoimmune diseases.

Though this is still new in the research landscape, Rountree said mTOR inhibition may improve immune function in elderly patients. Some research shows potential of calorie restriction, either chronic or intermittent fasting, as well as amino acid restriction and a ketogenic lifestyle. These are all possibilities for improving the aging process, Rountree said.

While Rountree said he does not claim to have the fountain of youth, he said the medical community is extensively researching the aging process and how to help people live well. He offered these potential strategies for life extension:

• Daily meditation
• Active social network
• Regular exercise, including high intensity interval training plus resistance training
• Dietary strategies, including calorie restriction, time-restricting feeding, intermittent fasting or a fasting-mimicking diet, and a ketogenic diet
• Hormone replacement

“There are so many ideas cooking,” Rountree said. “Age management has changed significantly, and while we’re still focused more on questions than answers, the top researchers are working to continue this progress.”