So what is Sirtuin?

The sirtuin (NAD+ dependent deacetylase) gene is a type of longevity gene that produces an enzyme that removes the acetyl group tail . Normally, when an acetyl group is attached to DNA , the corresponding gene is easily expressed, and when the acetyl group is removed, the expression of the gene is suppressed . The acetyl group is usually attached to genes that promote aging . The sirtuin enzyme removes some of the acetyl groups, turning off the aging genes or suppressing the genes that cause major diseases of aging, including cancer, to promote anti-aging .

“As we age, NAD decreases, and the resulting decrease in sirtuin activity is a major reason why diseases that were not present in youth appear in old age. ”

How to Live Longer According to <The End of Aging>

There are three main ways to prevent aging and live longer: lifestyle, longevity drugs , and advanced technology .

1. Improving lifestyle habits for longevity

▶ Eat less: By restricting calories or practicing intermittent or periodic fasting, we can awaken our body's survival circuits.

▶ Reduce meat consumption: Meat is essential for our bodies, but it is easy to overconsume it, and sometimes maintaining a state of amino acid deficiency rather than overconsumption will actually awaken the survival circuit and slow down aging.

▶ Sweating: Exercise is a stressful activity for the body, which increases NAD levels. Increased NAD levels activate survival circuits, increase energy production and muscle strength, and prevent aging by creating more capillaries that carry oxygen.

▶ Cooling the body: Cold activates brown fat, which protects the body, and brown fat increases SIRT3 in mitochondria supported by UCP protein, which will significantly reduce the incidence of diabetes, obesity, Alzheimer's disease, etc.

* SIRT3: Sirtuin 3 or NAD-dependent deacetylase sirtuin-3, a type of sirtuin

▶ Avoid disturbing the epigenetic landscape: It is best to avoid actions that may damage our survival circuits, such as ultraviolet rays, radiation, heavy fine dust, and various DNA expression.

2. Longevity drugs that reverse aging

The drugs presented in the book include rapamycin, metformin, resveratrol, NR (Nicotinamide riboside), and NMN (Nicotinamide mononucleotide) . These drugs are known to inhibit aging and restore vitality by activating enzymes associated with longevity. I will explain how each drug works to prevent aging.

(1) Rapamycin 's original use was as an antifungal agent, which has an immunosuppressive effect when used in high doses, but has a life-extending effect when used in relatively small doses. Rapamycin's mechanism of action is known to be to promote cell activation while inhibiting the TOR protein , which is involved in cell aging, thereby exerting an anti-aging effect.

It was in 2009 that rapamycin was discovered to be related to aging. Professor David Harrison of the Jackson Laboratory in the United States published a study in the international academic journal Nature examining the effects of rapamycin on longevity in mice. When the researchers administered rapamycin to mice at an age when the mortality rate was 90% , female mice saw a 14% increase in lifespan, and male mice a 9% increase . This study proved that rapamycin helps extend lifespan.

(2) Metformin was originally developed as a diabetes treatment, but extensive research has confirmed that metformin reduces mortality from pathological causes of aging, including cancer and cardiovascular disease, independent of its role in diabetes treatment. At the molecular level, metformin activates AMPK (AMPactivated protein kinase), thereby reducing ROS production and exerting an anti-aging mechanism.

* AMPK: Abbreviation for AMPactivated Protein kinase, an enzyme that plays an important role in maintaining cellular energy homeostasis. AMPK plays a role in cell activation, anti-aging, reducing inflammation, and increasing energy.

* ROS: Abbreviation for reactive oxygen species, which refers to active oxygen that attacks living tissues in the body. The more ROS there is, the more accelerated aging occurs.

Let's take a look at how effective metformin is as a longevity drug. The Metformin In Longevity Study (MILES) clinical trial was conducted to evaluate the drug's potential anti-aging effects. Data from the MILES trial, conducted on 14 elderly participants , showed that metformin altered several pathways associated with aging, including metabolic pathways, extracellular matrix (ECM) remodeling, adipose tissue and fatty acid metabolism, and mitochondria. These findings suggest that metformin targets multiple aging mechanisms .

(3) Resveratrol is found in abundance in red wine and is known to help with various diseases, including cancer, anti-viral, anti-aging, anti-inflammation, and life extension. Resveratrol has a life-extending effect by activating the SIRT1 (Sirtuin 1) gene .

* SIRT1: Sirtuin 1 or NAD-dependent deacetylase sirtuin-1, a type of sirtuin

A research team led by Dr. Jason R. B. Dicke of the Heritage Medical Research Institute at the University of Alberta in Canada published research on the anti-aging effects of resveratrol. They conducted a 12-week animal experiment in which they administered high doses of resveratrol to mice while performing wheel running exercise. The researchers found that resveratrol improved the mice's motor skills by 21% . These results suggest that resveratrol can improve motor skills, potentially preventing aging and making it a suitable longevity drug.

(4) NMN (Nicotinamide mononucleotide) or NR (Nicotine riboside) are both precursors of NAD. NAD (Nicotinamide adenine dinucleotide) is a coenzyme that helps chemical reactions within cells and is known to contribute to bioenergy production. NAD levels decrease with age. Conversely, when intracellular NAD levels increase, sirtuin genes are activated, improving brain, blood vessel, and muscle functions and reducing inflammation, thus preventing aging.

However, since NAD+ is a very large molecule that cannot enter cells directly , NMN or NR , which are converted to NAD+ in the body and can pass through cell membranes, are used as longevity drugs.

A clinical trial of NMN , conducted jointly by researchers at the University of Washington and Keio University in Japan, confirmed its anti-aging effects. NMN was administered daily to mice aged 5 to 17 months for one year. The results showed that, without any noticeable side effects, the mice burned more fat for energy than normal mice, and their muscles maintained a youthful state.

Tru Niagen®(NR) 300mg/day administration trial results

NR 's clinical efficacy can be confirmed in an eight-week administration trial conducted by KGK Science on obese individuals in their 40s. The clinical trial results for Tru Niagen® (NR) demonstrated that daily administration of 300 mg of NR increased NAD by approximately 51% after two weeks . This confirmed that NR is absorbed and converted into NAD in the body.

3. Revolutionary cutting-edge technology

Examples of cutting-edge technologies include senescent cell removal agents that only seek out and kill senescent cells, antiretroviral drugs that remove junk DNA and its remnants , anti-aging vaccines and cell reprogramming that completely reset our cells and bodies, literally rejuvenating them , personalized precision medicine represented by DNA sequencing and biomarker tracking , and 3D printing to produce customized body organs . All of these are cutting-edge technologies.

In <The End of Aging > , longevity goes beyond simply extending lifespan and talks about all of us living younger, healthier, and happier lives for a longer period of time .

Let's extend our happy lifespan by following Dr. Sinclair's longevity method .

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[References and Sources ]

[1] Resveratrol and its impact on aging and thyroid function, September 2011Journal of Endocrinological Investigation 34(10):788-92

[2] SPONSOR FEATURE Sponsor retains sole responsibility for the content of this article, Recent research into nicotinamide mononucleotide and aging, © 2021 Springer Nature

[3] A Closer Look into One of Our Clinical Studies