Fix Damaged DNA with NMN

Fix Damaged DNA with NMN

Everybody ages, but no one knows exactly why. What we do know is that increased fatigue, weakened bones and ill health walk in lockstep with aging, as does chronic disease.

Age is the number one risk factor for many diseases, including Alzheimer’s, cancer, cataracts, and macular degeneration. Researchers are making progress in understanding and treating each of these ailments, and in their understanding of the aging process itself.

DNA damage is a big part of the story. And now we know that NMN might help fix damaged DNA.

 In 2013, a group of Spanish scientists led by Dr. Carlos Lopez-Otin took a crack at identifying and explaining what they referred to as the "Hallmarks of Aging." They clearly showed that aging is the outcome of diverse and complex changes in normal biological functions, from dysfunction of proteins and altered communication - both within cells and among distant tissues in the body - to the accumulation of DNA damage.

In 2017, research led by scientists at Harvard Medical School revealed a critical step in a molecular chain of events that allows cells to fix damaged DNA. This occurred by taking a vitamin supplement called NMN that activated a DNA-repair molecule called NAD+ .

Before I review the Harvard study and what its conclusions might mean to your health, let's examine how DNA damage ages us.

DNA Gets Damaged As We Age

As we age, damage accumulates, including mutations and impairments in DNA repair processes. At the cellular level, decreases in the regenerative abilities of stem cells, impairments in mitochondrial function, and a tendency for proteins to misfold can all contribute to aging.

 
dna_with_nmn

Credit: DNA Repairs


In the case of DNA, as it replicates, the cellular machinery involved in the process makes mistakes, leading to changes in the DNA sequence. Mutagens such as reactive oxygen species (ROS or free radicals) or UV radiation can also damage DNA. Most of the time, DNA repair mechanisms fix the damage, but errors slip through and accumulate as we age. Aging has also been linked to the deterioration of DNA repair machinery, allowing permanent errors to become more common in older people.

Among many here are three ways DNA damage affects us:

(1) When DNA has become too damaged, cells kill themselves or enter a nonreplicating state, which is called senescence. Though largely dormant, senescent cells may speed the aging process by secreting inflammatory cytokines thought to contribute to atherosclerosis and other aging-related diseases.

(2) DNA scaffolding proteins that typically help stabilize the genome (our genetic material) show changes with age, contributing to impaired cell division, increased senescence, and other aging-related processes.

(3) Telomeres may be especially prone to DNA damage and lose their ability to protect the body from cancer and protect chromosomes from fusing with one another.

Obviously, helping the body repair its DNA damage is a big step to aging more slowly and extending healthspan, if not lifespan. That's why the findings of the Harvard study are so important.

 


Credit: Medicalxpress.com

Harvard Shows NMN Boosts NAD+ and Protects DNA

Published March 24, 2017 in Science, the Harvard study offers important insights into how and why the body’s ability to fix damaged DNA dwindles over time. It also shows that the signaling molecule NAD+ is a key regulator of protein-to-protein interactions in DNA repair. Experiments conducted on mice show that treatment with the NAD+ precursor NMN mitigates age-related DNA damage and wards off DNA damage from radiation exposure.

If affirmed in further animal studies and in humans, the findings can help pave the way to therapies that prevent DNA damage associated with aging. In addition, they may help with cancer treatments that involve radiation exposure and some types of chemotherapy, which along with killing tumors, can cause considerable DNA damage in healthy cells.

Dr. David Sinclair, senior author of the study said:

"Our results unveil a key mechanism in cellular degeneration and aging, but beyond that they point to a therapeutic avenue to halt and reverse age-related and radiation-induced DNA damage."(1)

Dr. Sinclair is a professor in the Department of Genetics at Harvard Medical School, co-director of the Paul F. Glenn Center for the Biology of Aging, and professor at the University of New South Wales School of Medicine in Sydney.

See what he says about the Harvard Study:


Interestingly, Dr. Sinclair and his family consume NMN daily. Before he started consuming NMN, the then 47-year-old Professor Sinclair had his blood tested and was told his body had a biological age of 58. After taking a 500 mg NMN pill every morning for three months, he was tested again and his biological age was 32. (2) Now, as Dr. Sinclair told Joe Rogan in an interview, he and his family have increased their dose from 500 mg to one gram of NMN per day. (3)

Dr. Sinclair obviously believes that the benefits conferred to the mice he studied that consumed NMN will also occur in people. That's because NMN stimulated NAD+ which in turn boosts the activity of SIRT1.

The NAD+/NMN Chain Reaction

At the outset, the Harvard researchers knew that NAD+ is needed to boost the activity of the SIRT1 protein, which delays aging and extends life in yeast, flies, and mice. The problem is that NAD+ declines steadily in all animals as we age, including us. Given that both SIRT1 and PARP1 (a protein known to control DNA repair) consume NAD+ in order to do their work, less NAD+ means fewer health benefits conferred by SIRT1 and PARP1.

A sirtuin is a type of protein involved in regulating cellular processes including the aging and death of cells and their resistance to stress. SIRT1 refers to the first of seven sirtuins that are in mammals. PARP1 is one of a family of proteins involved in a number of cellular processes such as DNA repair, genomic stability, and programmed cell death.

SIRT1 and PARP1 are big players in maintaining a mammal's vitality, but as mentioned, both of these proteins require NAD+ to function. To increase NAD+ levels, the researchers treated young and old mice with the NAD+ precursor NMN, which makes up half of an NAD+ molecule. NAD+ is too large to cross the cell membrane, but NMN can slip across it easily. Once inside the cell, NMN binds to another NMN molecule to form NAD+.

As expected, old mice had lower levels of NAD+ in their livers, lower levels of PARP1. After receiving NMN with their drinking water for a week, however, old mice showed marked differences both in NAD+ levels and PARP1 activity. NAD levels in the livers of old mice shot up to levels similar to those seen in younger mice. The cells of mice treated with NMN also showed increased PARP1 activity. Overall, the mice showed a decline in molecular markers that signal DNA damage.

NMN Lowers Damage Caused By Radiation

In a final step, the Harvard scientists exposed mice to DNA-damaging radiation. Cells of animals pre-treated with NMN showed lower levels of DNA damage. Such mice also didn’t exhibit the typical radiation-induced aberrations in blood counts, such as altered white cell counts and changes in lymphocyte and hemoglobin levels. The protective effect was seen even in mice treated with NMN after radiation exposure.

Taken together, the results shed light on the mechanism behind cellular demise induced by DNA damage. They also suggest that restoring NAD levels by NMN treatment should be explored further as a possible therapy to avert the unwanted side effects of environmental radiation, as well as radiation exposure from cancer treatments.

 


 

Joe GarmaJoe Garma has written more than 670 articles on his anti-aging blog, GarmaOnHealth, and is currently writing a book, The Ageproof Method, 12 Biohacks for A Long and Strong Life. Prohealth Longevity readers can get his four-part guide, Transform Your Body and Mind here.

 


 

References

  1. Harrison Wein, Ph.D.: Researchers find clue to repair of aging DNA
  2. George Tait Edwards: How To Live A Healthy Long Life
  3. Joe Rogan Experience #1234 - David Sinclair: https://www.youtube.com/watch?v=HOTS0HS7aq4

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