Dr Thanh-Tam Pham - 25/07/2021

Our DNA is constantly under attack. On average, each of our fourty-six chromosomes is broken in some way every time a cell copies its DNA, that occurs during replication. Others are caused by natural radiation, chemicals, chemicals in our environment, and the X rays and CT scans. If we did not have a way to repair our DNA, we would not last long.

Aging, we’ve long been told, is simply the process of growing old. And growing old has long been seen as an inevitable part of life.

There are some simple tests to determine how biologically old you are. If you are over 45 and can do more than twenty push-ups, you are doing well. The other test is the sitting-rising test (SRT). Sit on the floor, barefooted, with legs crossed. Lean forward quickly and see if you can get up in one move. A middle-aged person typically needs to push off with one of their hands. An elderly person often needs to get onto one knee.

The older we get, the less it takes for an injury or illness to drive us to our deaths.

Dr David Sinclair believe that aging is a disease and is treatable. There are no biological, chemical, or physical laws that say life must end.

When we stay healthy and vibrant, as long as we feel young physically and mentally, our age doesn’t matter. And feeling younger than your age predicts lower mortality and better cognitive abilities later in life.

1- Calorie restriction:

Many studies demonstrated that calorie restriction without malnutrition leads to longevity for all sorts of life-forms. It also prevents cardiac disease, diabetes, stroke and cancer.

Intermittent fasting is also shown to increase longevity.

Being hungry helps turn on genes in the brain that release longevity hormones according to a study by Dongsheng Cai at the Albert Einstein College of Medicine.

2- Amino acids:

Amino acids serve as the building blocks for every protein in the body. There are nine essential amino acids that our bodies cannot make, and meat contains all nine of them. Studies have demonstrated that heavily animal- based diets are associated with high cardiovascular mortality and cancer risks. Those amino acids can be obtained by consuming plant-based protein sources but they are in a smaller amount. Limiting the intake of amino acids especially methionine, arginine, leucine, isoleucine and valine correlate with increase lifespan. Vegetarians suffer significantly lower rates of cardiovascular disease and cancer than meat eaters, but we may live longer but not maximizing our lifespan.

3- Exercise:

Most doctors thought that exercise improves health only by moving blood through the circulatory system faster, flushing out the building of plaque. But at the cellular scale, it was found that those that exercised more had longer telomeres. Exercise applies stress to our bodies. It raises NAD levels, which in turn activates the survival network, which turns up energy production and forces muscles to grow extra oxygen- carrying capillaries. The longevity regulators and sirtuins help extend telomeres protecting DNA from degradation.

Exercise 15 min a day can reduce the chance of heart attack in studies.

To engage our longevity genes fully, intensity does matter. High intensity interval training that raises heart and respiration rates, engages the greatest number of health promoting genes. In other words: exercise turns on the genes to make us young again at a cellular level.

4- Cold exposure:

Exercising in the cold appears to turbo-charge the creation of brown adipose tissue by stressing the longevity genes. As with most things in life, it is probably best to change your lifestyle when you are young, because making brown fat becomes harder as you get older. Studies have shown there is correlation between brown fat and longevity. Animals subjected to shivering cold for 3 hours a day have reduced rate of diabetes, obesity and Alzheimer’s disease.

5- Avoid harmful factors:

DNA damage caused by chemicals such as cigarette smoking, keeps the DNA repair crews working overtime and the result is the epigenetic instability that causes aging.

Other chemicals are car exhaust, PCBs in plastics, solvents, pesticides, degreasers… can also damage our genomes. Nitrates in processed meats are carcinogenic.

Radiation such as UV light, X rays, gamma rays can cause additional DNA damage.

6- Drugs and Nutraceuticals:

Life can potentially last forever, as long as it can preserve critical biological information and absorb energy from somewhere in the universe.

The 3 main longevity pathways, mTOR (mechanistic target of Rapamycin), AMPK (activated protein kinase- a sensor of low ATP levels in cells) and Sirtuins (signaling proteins involved in metabolic regulation) evolved to protect the body during time of adversity by activating survival mechanisms. When they are activated, either by low calorie or low amino acid diets, or by exercise, organisms become healthier, disease resistant and lived longer.

         ●    Metformin is widely used for treatment of diabetes and showed increase lifespan in mice, reduced LDL and improved physical performance. Metformin limits metabolic reactions in mitochondria, slowing down the process of cells converting macronutrients into energy. The result is the activation of AMPK, an enzyme known for its ability to respond to low energy levels and restore the function of mitochondria. It makes more NAD and also activates sirtuins and other defenses against aging. Metformin inhibits cancer cell metabolism, increases mitochondrial activity and removes misfolded proteins. A study showed Metformin reduced the likelihood of dementia, cardiovascular disease, cancer, frailty and reduce cancer incidence.

         ●    Antioxidants: fisetin, resveratrol in grapes experiencing stress, were found to increase lifespan of mice. Plants have survival circuits too, so when stressed, they produce chemicals for themselves that tell their cells to hunker down and survive. Organic foods are often grown under more stressful conditions might be better for us.

         ●    NAD (a coenzyme central to metabolism) levels decrease with age throughout the body, in the brain, blood, muscle, immune cells, pancreas, skin and even the endothelial cells of blood vessels. NAD is so central to so many fundamental cellular processes.

NR (Nicotinamide riboside) a form of vitamin B3 and NMN (nicotinamide mononucleotide) in avocado, broccoli and cabbage were shown to boost NAD levels. NMN in mice was found to treat the symptoms of diabetes in old mice by restoring the NAD levels, increase the endurance of old mice, improve balance, coordination, speed, strength and memory too.

         ●   Senolytics:

The key hallmark of aging is the accumulation of senescent cells. These cells have permanently ceased reproduction

Short telomeres made the DNA at the end of the chromosome to be exposed and the cell detects the DNA and think it is a DNA break and try to repair it, sometimes fusing 2 ends of different chromosome together. Senescent cells are often referred as “zombie cells” because even they should be dead, they refuse to die. When we have a lot of senescent cells in the body, it is a clear sign that aging is getting a strong grip on us. These cells continue to release proteins called cytokines that cause inflammation and attract immune cells called macrophages that then attack the tissue. Chronic inflammation gives rise to multiple sclerosis, inflammatory bowel disease, psoriasis and it is also plays a role in heart disease, diabetes and dementia. Cytokines can cause other cells to become zombie and they can stimulate surrounding cells to become a tumour and spread.

A class of pharmaceuticals called senolytics are zombie killers. Quercetin (in capers, kale, red onions) and a drug called dasatinib (chemotherapy for leukemia) can eliminate senescent cells in mice and extend their lifespan by 36 percent.


Lifespan: Why we age – and why we don’t have to- By Dr David Sinclair- PhD