Telomeres for Reversing the Aging Process

Aging is inevitable. But your biological age can be quite different from your chronological age, and your telomeres have a lot to do with your biological aging. Everyday our DNA suffers millions of damaging. Fortunately, our cells have powerful mechanisms to repair those damages. However, when the telomere becomes too short, it can no longer protect the cell’s DNA. Telomeres act as the aging clock in every cell. In young humans, telomeres are about 8,000-10,000 nucleotides long. They shorten with each cell division. Proper telomere maintenance is the secret of youthfulness. Although genetics play an important role in determining telomere length, lifestlyle, diet and exercises are the key elements to extend telomeres and reverse the aging process. There are many scientific evidence that support the protective effects of high fruit and vegetable consumption on the risks of many age-related diseases.

Cause of Aging:

reverse-agingThe cause of aging is one of the most fundamental questions in biology. Currently, there is no single theory that clearly explain as to what the causes of aging are and how they behave across the life span. However, I am explaining here, the four most dominant theories of aging. These four theories of aging are apparently isolated but in reality they are interlinked. More than 300 theories of aging have been postulated. Among those, the free radical theory of aging is one of the most prominent and well studied.

Cellular Senescence Theory of Aging:

Cells continually experience stress and damage from exogenous and endogenous sources, and their responses range from complete recovery to cell death. For growth, cellular division is must. However, as cells mature they naturally stop dividing and enter into a period called senescence. Most cells cannot divide indefinitely due to a process termed cellular or replicative senescence. Most normal human cells undergo cellular senescence after accruing a fixed number of cell divisions. Senescence represents a safety mechanism to suppress tumour progression. Cellular senescence is important for tumor suppression. However, cellular senescence contributes to aging. A growing body of evidence demonstrates that the accumulation of senescent cells is a probable aging mechanism. Cellular senescence is the result of telomere shortening that ultimately triggers a DNA damage response.

Sirtuins Theory of Aging

The silent information regulator (SIR) gene family of proteins is conserved from bacteria to humans. Many studies on yeast and mice demonstrated that caloric restrictions increase life span. The gene that was responsible to increase life span is SIR2. SIR2 appeared to stop the aging process by stopping the production of waste material in the cell, which allowed the cell to work better for longer.

Humans don’t have SIR2, but we have a equivalent gene known as SIRT1.  SIR2 and SIRT1 is collectively known as sirtuins. In mammals, the sirtuin family has seven members (SIRT1-7).  The main function of sirtuin proteins is to promote survival and stress resistance, resulting in longevity. SIRT1 promotes replicative senescence under conditions of chronic stress. It is widely reported that SIRT1 can promote not only carcinogenesis but also metastasis and insulin resistance, and have beneficial effects in metabolic diseases, mediate high-density lipoprotein synthesis and regulate endothelial nitric oxide to protect against cardiovascular disease.  One potential sirtuin regulator receiving a good deal of attention is resveratrol. Resveratrol is available on the skin of grapes, blueberries, raspberries, and mulberries.

Mitochondrial dysfunction is linked with aging and age related diseases. There is increasing research evidence that mitochondrial sirtuins (SIRT3–5) regulates aging and age related diseases.

The SIRT3 gene is known as a mitochondrial gene. SIRT3 gene reduces oxidation, suppresses tumor growth and helps to renew old mitochondria in a process called mitogenesis. SIRT3 has received much attention for its role in metabolism and aging. SIRT3 prevents apoptosis by lowering reactive oxygen species and inhibiting components of the mitochondrial permeability transition pore. SIRT3 protein levels in skeletal muscle are sensitive to diet. SIRT3 exhibits high expression in important metabolically active tissues like kidney, heart, liver, and brain.  SIRT3 expression increases by exercise,  fasting and caloric restriction and decreased by high-fat diet.

SIRT1, SIRT2, and SIRT3 have deacetylase activity. Deacetylation is simply the reverse reaction where an acetyl group is removed from a molecule. Their dependence on NAD(+) directly links their activity to the metabolic status of the cell. High NAD(+) levels convey neuro-protective effects. Sirtuins are a conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases that regulate lifespan in many model organisms including yeast and mice.

Recent work suggests that sirtuins can modulate ROS levels notably during a dietary regimen known as calorie restriction which enhances lifespan for several organisms. Although both sirtuins and ROS have been implicated in the aging process.  Sirtuins can modulate ROS levels notably during a dietary regimen known as calorie restriction which enhances lifespan for several organisms. Although both sirtuins and ROS have been implicated in the aging process, their precise roles remain unknown.

Sterile-inflammation Theory of Aging:

Normally, inflammation is a powerful homeostatic mechanism, aimed at maintaining and restoring tissue integrity. Inflammation promote tissue repair. Inflammation is tightly regulated by the body, too little inflammation could lead to progressive tissue destruction. In contrast, chronic inflammation may lead to a host of diseases, such as hay fever, periodontitis, atherosclerosis, rheumatoid arthritis etc.

Aging alters inflammatory responses. Accumulating evidence indicates that aging is associated with a chronic low-level inflammation, termed sterileinflammation. Sterile-inflammation is a form of pathogen-free inflammation caused by mechanical trauma, ischemia, stress or environmental conditions such as ultra-violet radiation. Sterile chronic inflammation also triggers a homeostatic response in macrophages that suppresses their ability to respond to invading bacteria.

Mitochondrial Theory of Aging

The mitochondria are arguably the most awesome microscopic machines in biology. They  are often referred to as the cell’s “powerhouse,” generating chemical energy to carry out essential biological functions. They are the engines of our cells. They convert fats and sugars into cellular energy. Mitochondrial energy production is accompanied by a low level of the aberrant production of reactive oxygen species (ROS) that damage mitochondria DNA and proteins. More than 90% of the oxidation that occurs within living cells occurs within the mitochondria.  By age 80 only about 4% of mitochondria are fully functional.

This theory speculate that cumulative damage to mitochondria and mitochondrial DNA (mtDNA) caused by ROS is the main cause of aging. Reactive oxygen species (ROS) are highly reactive molecules that consist of a number of diverse chemical species including superoxide anion (O2−), hydroxyl radical (OH), and hydrogen peroxide (H2O2). As ROS are generated mainly as by-products of mitochondrial respiration, mitochondria are thought to be the primary target of oxidative damage and play an important role in aging.

Functional decline of neutrophil is one of the dominant theories of aging.  Neutrophils are the most abundant white blood cells in humans; they account for approximately 50-70% of all white blood cells (leukocytes). Neutrophil forms the first line of defense against bacteria and fungi. The average lifespan of human neutrophil  is about 5.4 days.

Reversing the Aging Process Techniques:

Generally, aging is characterize by graying hair, loss of hair, increase curvature of the spine, loss of eyesight, decline in immune system, loss of frailty, and loss of cognition. However, healthy aging is reduction of these biological processes. There are about 50 to 70 billion cell death each day due to apoptosis (programmed cell death) in the average human adult. Both over and under apoptosis causes age-related diseases.

There are five major theories for slowing the aging process. They are: free radical theory, telomere length theory, mTOR signaling pathway theory, sirtuin theory and senescence-associated secretory phenotype (SASP) theory.

Free radical theory of aging:

free-radicals-oxygenOne of the most popular theories on aging is the free radical theory. According to the free radical theory of aging (FRTA), the main causes of the aging process seem to be related to reactive oxygen species and free radicals, such as superoxide anion, hydrogen peroxide, hydroxyl radicals, and singlet oxygen. When oxygen is used to make energy in human cells, it releases reactive compounds called free radicals, also called reactive oxygen species (ROS).   The organisms age because cells accumulate free radical damage over time. A free radical is any atom or molecule that has a single unpaired electron in an outer shell. In some model organisms, such as yeast and Drosophila, there is evidence that reducing oxidative damage can extend lifespan. Reactive oxygen species (ROS) are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. During times of environmental stress (e.g., UV or heat exposure), ROS levels can increase dramatically.This may result in significant damage to cell structures.

The key antioxidants we need to take include vitamin C, E, and A, along with the carotenoids like beta-carotene. Two of biggest classes of antioxidants that destroy free radicals are polyphenols and flavonoids.  Both these antioxidants neutralize the free radicals before they can damage your body’s cells.

Neuroendocrine Theory of Aging:

neuroendocrinetheory_agingHormones are vital for repairing and regulating our bodily functions, and when aging causes a drop in hormone production, it causes a decline in our body’s ability to repair and regulate itself as well. Moreover hormone production is highly interactive. The drop in production of any one hormone is likely to have a feedback effect on the whole mechanism, signaling other organs to release lower levels of other hormones which will cause other body parts to release lower levels of yet other hormones.

The homeostatic balance—which appears to reach its optimum at ages 20 to 25—continues to shift, resulting in more (i.e., cortisol, insulin) or less than optimum (i.e., estrogen, testosterone) levels of many hormones, and ultimately, the exhaustion of the peripheral endocrine glands due to their prolonged efforts to overcome the loss of hypothalamic sensitivity.

What are Telomeres?

A telomere is a region of repetitive DNA at the end of a chromosome, which protects the end of the chromosome from deterioration. Telomeres are like caps at the end of each strand of DNA which protect the chromosomes. Before going into the details of telomeres, let us understand the basic difference between DNA, genes and chromosomes.

DNA, Genes and Chromosomes

Chromosomes, genes and DNA are like strings of plastic beads. The whole strand of beads represents the chromosome, each bead might represent a gene, and the plastic from which the beads are made would be the DNA molecules.

What is DNA?

A DNA ( DeoxyriboNucleic Acid ) is a bio molecule that carries the genetic information. Adenine (A), Guanine (G), Cytosine (C), and Thymine (T) are the four chemical building blocks of the DNA molecule known as base.  Our genes are composed of DNA and these molecules (A, G, C and T) are repeated again and again—three billion times in every complete set of chromosomes.

What are Genes?

Gene is the basic physical and functional unit of heredity. Our genes are made up of DNA. Genes are specific sequences of DNA located on chromosomes that provide instructions to make proteins. There are approximately 30,000 genes that influence our growth and development. Each gene occupies a specific location on a chromosome. With the exception of the X and Y chromosomes, there are two copies of each chromosome and therefore two copies of each gene.

What are Chromosomes?

Our bodies are composed of millions of cells. Within the center of each cell are rod-like structures known as chromosomes. Typically, there are 46 chromosomes in each cell. They are grouped into 23 pairs, one member of each pair coming from our mother and the other from our father at the time of conception. The first 22 pairs of chromsomes are the same in both men and women and are number 1 through 22. The last two determine our sex and are call X and Y. Women have two X chromosomes and men have one X chromosome and one Y chromosome.

As we grow, our bodies duplicate the cells through cell divisions. This process is called mitosis. Mitosis is a process that allows one “parent” cell to divide into two new “daughter” cells. DNA is a molecule which stores genetic information. Chromosomes are made up of DNA, and some parts of a chromosome are genes. TTAGGG

Recently, scientists examined how telomere length changes with age in vivo. They observed that telomere length change with age in vivo differs among individuals and in different cell types and is influenced by telomerase activity and changes in physiological conditions [4].

Metabolic reprogramming: Means to prevent telomere shortening

metabolic-reprogrammingInterventions that extend lifespan act through metabolic reprogramming, thereby changing both damage composition and the rate of damage accumulation. Caloric restriction can increase the life span of several mammalian species, including the rhesus monkey.  showed that one of these genes, SIRT1, was activated by the compound resveratrol, which is found in grapes, red wine and certain nuts. The following means can prevent telomere shortening:

– A healthy diet and nutrition will prevent telomere shortening as well and also lead to telomere lengthening.
– Exercise is the simple means to prevent telomere shortening.
– Reprogram your vision of old age.
– Don’t be afraid to make a big change in life for betterment
– Never say you’re too old
– Keep your brain active.
– Physical activity, social engagement and focusing will help you stay mentally sharp.
– Take Vitamin C,A, E and D3
– Omega-3 and polyphenols
– Stay away from red meats and processed foods
-T-65, an extract from astragalus has been shown in vitro to lengthen telomeres, but there is no publication yet about in vivo effects in humans.
-Resveratrol is useful to prevent shortening of telomeres as well.

 

References:

1. Telomeres of Human Chromosomes, Nature
2.Telomerase reverses ageing process, Nature
3. Nettleton, Jennifer et al., 2008. Dietary Patterns, Food Groups, and Telomere Length in the Multi-Ethnic Study of Atherosclerosis (MESA). The American Journal of Clinical Nutrition.
4. Yun Lin et al., 2015 Age-associated telomere attrition of lymphocytes in vivo is co-ordinated with changes in telomerase activity, composition of lymphocyte subsets and health conditions.,Clinical Science

5. Coming of age: molecular drivers of aging and therapeutic opportunities

 

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