 In agreement with the last report of the UN on `Aging of the
World-wide Population”, published in 2009, the humanity has...
The science of aging is among the most dynamic and
provocative in modern biology. Over the past two
decades we have seen a...
Aging is the progressive loss of physiological functions that
increases the probability of death…..

* The decline in func...
Loss of structure and function in aging.
Figures represent percentage of a given function remaining in an average 75year-o...
LEADIND CAUSES OF DEATH IN MEN AND WOMEN
Men
01
02
03
04
05

06
07
08
09
10

Heart disease
Cancer
Accidents

Women

Heart ...
Programmed in our genes
* Single genes that increase life span in Drosophila,C.elegans, and
mice.
* Genes that suppress si...
The increased life span of yeast

Calorie restriction requires a gene called SIR2 ("Silent
Information Regulator 2")encode...
*Calorie restriction in mice causes
* A drop in
* The level

of circulating insulin and insulin-like growth
factor-1 (Igf-...
* A major aspect of metabolism is the oxidation of foodstuffs by
the mitochondria

* Electron transport in the mitochondri...
Food

Link to the
Genes

Specific Gene

Green Tea

Helps to inhibit
genes that fuel
breast cancer

HER-2

Broccoli

Boosts...
The
Accumulation of
Senescent Cells

Chronic

REPLICATIVE

senescence

senescence
*Cells unless they retain the enzyme telomerase

*

Lose DNA from the tips of their chromosomes
with each cell division.
T...
P53
P16INK4a
Mice whose genes for telomerase have been "knocked out"
1: The number of Mitochondria in their cells decreases as does the...
* Effect of

radiation on aging
 Mice given ionizing radiation that damages DNA show early
aging.
 Transgenic mice with a defect in the "proofreading" f...
 Cells taken from old mice (and old humans) show slightly
elevated levels of somatic mutations and chromosome
abnormaliti...
Interactions:

*Telomere shortening activates p53 which leads to
damaged mitochondria.

*The inefficient electron transpor...
* Gene expression declined in old age for many genes. Some
examples:

* Genes encoding proteins involved in synaptic activ...
Clues from Premature Aging Syndromes

* Werner's syndrome-The hair of patients turns gray in their 20s
and most die in the...
 Ataxia telangiectasia (AT)-These patients show signs of
premature aging. They lack a functioning gene (ATM)
product need...
SOME MODEL ORGANISNS USED IN LONGEVITY
RESEARCH

* Single mutants in Caenorhabditis elegans can reduce mortality

threefol...
*The nematode affect mitochondrial function, the so-called
Mit mutants. Starting with the identification of clk-1, and
now...
Drosophila melanogaster, respectively. sir-2 encodes an
NAD-dependent protein deacetylase, which might mediate
the lifespa...
* Many candidate genes have been investigated for putative
associations with human survival or longevity.

Cardiovascular ...
*In

lipoprotein metabolism, microsomal triglyceride
transfer protein (MTTP), has also been implicated
in human longevity....
* Immune system genes
* The multifunctional cytokine interleukin 6 (IL6) is

central to this inflammation, and is overexpr...
* Linkage analysis

* Case–control studies

* Longitudinal studies
Outlook: the future of human longevity genetics

* Although there are many biologically plausible

candidates for genes th...
 These studies assess long-lived siblings and controls,
and some of these also include intermediate
phenotypes such as ca...
The record holder of maximum longevity belongs to France's Jeanne
Calment,who lived to be 122 years and 164 days old. Long...
*"Genes are not destiny!" ~ Bruce Lipton, Ph.D.
*The development of an understanding of the true factors

of longevity too...
 However, we are beginning to see changes. The scientists and academics
are beginning to come out with this "new biology"...
By:
Nazish Nehal,
M. Tech (Biotechnology),
University School of Biotechnology (USBT),
Guru Gobind Singh Indraprastha Unive...
Ageing and its relationship with longevity genes
Ageing and its relationship with longevity genes
Ageing and its relationship with longevity genes
Ageing and its relationship with longevity genes
Ageing and its relationship with longevity genes
Ageing and its relationship with longevity genes
Ageing and its relationship with longevity genes
Ageing and its relationship with longevity genes
Ageing and its relationship with longevity genes
Ageing and its relationship with longevity genes
Ageing and its relationship with longevity genes
Ageing and its relationship with longevity genes
Ageing and its relationship with longevity genes
Ageing and its relationship with longevity genes
Ageing and its relationship with longevity genes
Ageing and its relationship with longevity genes
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Ageing and its relationship with longevity genes

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By:
Nazish Nehal,
M. Tech (Biotechnology),
University School of Biotechnology (USBT),
Guru Gobind Singh Indraprastha University,
New Delhi (INDIA)

Published in: Health & Medicine, Technology
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Ageing and its relationship with longevity genes

  1. 1.  In agreement with the last report of the UN on `Aging of the World-wide Population”, published in 2009, the humanity has improved its environmental conditions from the century last, managing to increase the duration of the life in the developed countries, of 15 years for the men and 22 years for the woman.  Nevertheless, the human beings we are limited to live an average on 100 years, although exceptional cases of 150 years have been registered. But some investigators think that we are not programmed to die, which has impelled to the new science of the biogerontología to give with the possible keys of the rejuvenation.  The human being owns a genetic clock that seems to determine the time of life, but the process does not happen in the same way in all the individuals. These genetic variants associated with the aging, would explain because some people seem to age more express than others, according to the Nature magazine of February of 2010.
  2. 2. The science of aging is among the most dynamic and provocative in modern biology. Over the past two decades we have seen a virtual explosion in research investigating the molecular and behavioral systems that control the aging process. But the more researchers uncover about the science of aging, the more questions emerge.
  3. 3. Aging is the progressive loss of physiological functions that increases the probability of death….. * The decline in function certainly occurs within cells. This is especially true of cells that are no longer in the cell cycle * Neurons in the brain * Skeletal and cardiac muscle * Kidney cells Random mortality from * Starvation * Predation * Infectious disease * A harsh environment (e.g.. cold) * Kills off most animals long before they begin to show signs of aging. * Even for humans, aging has only become common in recent decades
  4. 4. Loss of structure and function in aging. Figures represent percentage of a given function remaining in an average 75year-old man compared with that found in an average 30-year-old man, the latter value taken as 100%. Weight of brain Blood supply to brain Output of heart at rest 56% 80 70 Number of glomeruli in kidney 56 Glomerular filtration rate 69 Speed of return to normal pH of blood after displacement 17 Number of taste buds Vital capacity Strength of hand grip 36 56 55 Maximum O2 uptake during exercise 40 Number of axons in spinal nerve 63 Velocity of nerve impulse Body weight 90 88
  5. 5. LEADIND CAUSES OF DEATH IN MEN AND WOMEN Men 01 02 03 04 05 06 07 08 09 10 Heart disease Cancer Accidents Women Heart disease Cancer Stroke Chronic obstructive Stroke lung disease Chronic obstructive lung disease Diabetes Diabetes Alzheimer's disease Pneumonia and influenze Accidents Pneumonia and Suicide influenze Kidney disease Kidney disease Live disease Blood infections
  6. 6. Programmed in our genes * Single genes that increase life span in Drosophila,C.elegans, and mice. * Genes that suppress signaling by insulin and insulin-like growth factor-1 (Igf-1) increase life span in these animals. * Examples: * Mice with one of their Igf-1 receptor genes “Knocked out" live 25% longer than normal mice. * Antagonistic pleiotrophy. Genes that promote survival early in life at the expense of maintaining the body will be selected. * Some examples: By forcing cells with damaged DNA to stop dividing and become senescent or even to die by apoptosis, it protects the organism from the threat of those cells becoming cancerous but at the expense of reducing cell renewal
  7. 7. The increased life span of yeast Calorie restriction requires a gene called SIR2 ("Silent Information Regulator 2")encodes the Sir2 Deacetylase, an enzyme Removes acetyl groups from proteins. Increasing the activity of Sir2 extends the life span of yeast, C.elegans, and Drosophila. But it turns out that mammals have 7 genes that encode proteins — called sirtuins — similar to Sir2.
  8. 8. *Calorie restriction in mice causes * A drop in * The level of circulating insulin and insulin-like growth factor-1 (Igf-1) * The * The level of glucose and triglycerides in the blood level of NADH (produced by cellular respiration) within cells This leads to: * The production of sirtuins to increase markedly * Apoptosis of cells to be inhibited * Formation of Adipose tissue to be suppressed * Increased production of nitric oxide(NO) which is essential for the benefits of CR to take effect * Greatly increased physical activity and lower body weight
  9. 9. * A major aspect of metabolism is the oxidation of foodstuffs by the mitochondria * Electron transport in the mitochondria generates reactive oxygen species ("ROS") such as * The superoxide anion (O2-), which generates * Hydrogen peroxide (H2O2) * Although cells contain enzymes catalase which breaks down H2O2 they eventually and inevitably damage macromolecules in the cell * Proteins * Lipids
  10. 10. Food Link to the Genes Specific Gene Green Tea Helps to inhibit genes that fuel breast cancer HER-2 Broccoli Boosts genes that protect against heart disease Soybeans Affect 123 genes in- volved in prostate cancer Turmeric (a curry ingredient) Suppresses genes that bump up inflammation GST p53 Cox-2 Function of the Gene Long-term Effect Triggers growth Slow HER-2 signals in cells signaling in tumors Produces the body's master antioxidant glutathione The additional glutathione helps keep arteries healthy Increase activity of the p53 gene to Kill mutant cells block tumor formation Makes inflammatory compounds Help to ward off heart disease, colon cancer and Alzheimer's
  11. 11. The Accumulation of Senescent Cells Chronic REPLICATIVE senescence senescence
  12. 12. *Cells unless they retain the enzyme telomerase * Lose DNA from the tips of their chromosomes with each cell division. The telomeres in the cells of old animals-SHORTER than in young cells. *Cells genetically manipulated to express telomerase long after they should have stopped- avoid replicative senescence. *If telomeres get too short (< 13 repeats in human cells), chromosome abnormalities — a hallmark of CANCER — NO Cancer if the cell ceases to divide. So telomere shortening may protect against cancer at the price of cell senescence.
  13. 13. P53 P16INK4a
  14. 14. Mice whose genes for telomerase have been "knocked out" 1: The number of Mitochondria in their cells decreases as does the function of those that remain. * * * Oxygen consumption and ATP production declines. The efficiency of the electron transport chain decreases. This leads to an increased generation of reactive oxygen species(ROS) 2: The level of P53 activity increases. * * * mitosis declines Apoptosis of cells increases Replicative senescence increases 3: The anatomy and function of organs such as the liver and heart show the degenerative changes of age.
  15. 15. * Effect of radiation on aging
  16. 16.  Mice given ionizing radiation that damages DNA show early aging.  Transgenic mice with a defect in the "proofreading" function of the DNA polymerase responsible for copying mitochondrial DNA accumulate many mutations in their mitochondrial genes; show marked signs of premature aging.
  17. 17.  Cells taken from old mice (and old humans) show slightly elevated levels of somatic mutations and chromosome abnormalities like translocations and aneuploidy. Many of these changes also cause cancer so it is no accident that the incidence of cancer rises with advancing age (graph). The hematopoietic stem cells of knockout mice deficient in any one of these enzymes needed for genome maintenance  XPD for nucleotide excision repair (NER)  Ku80 for nonhomologous end joining (NHEJ)  TR (telomerase RNA) needed for telomere maintenance lose their ability to supply the various progenitor cells that produce the white blood cells
  18. 18. Interactions: *Telomere shortening activates p53 which leads to damaged mitochondria. *The inefficient electron transport chain in damaged mitochondria produces ROS. *Abundant nutrients (e.g. amino acids) as well as other growth stimulants activate TOR which promotes anabolism (protein and lipid synthesis) with attendant production of reactive oxygen species (ROS) and aging. *Calorie restriction, working through SIRT1 inhibits TOR and its downstream effects. *Inhibition of TOR relieves its inhibition of autophagy allowing the cells to scavenge, for example, damaged mitochondria.
  19. 19. * Gene expression declined in old age for many genes. Some examples: * Genes encoding proteins involved in synaptic activity in the brain (e.g., learning, memory) * NMDA, AMPA, GABA receptors * calcium- calmodulin-dependent kinase II (CaMKII) * Genes involved in mitochondrial functions, such as * Production of ATP (needed for DNA repair) * Production of damaging reactive oxygen species (ROS)
  20. 20. Clues from Premature Aging Syndromes * Werner's syndrome-The hair of patients turns gray in their 20s and most die in their late 40s with such signs of age as osteoporosis, cataracts, and atherosclerosis. * Cockayne syndrome (CS)-. While these people show only some of the signs of aging, they do have a sharply-reduced life span.
  21. 21.  Ataxia telangiectasia (AT)-These patients show signs of premature aging. They lack a functioning gene (ATM) product needed to detect DNA damage and initiate a repair response.  Hutchinson-Gilford progeria syndrome-. Caused by mutations in the gene (LMNA) for lamin the intermediate filament protein that stabilizes the inner membrane of the nuclear envelope.
  22. 22. SOME MODEL ORGANISNS USED IN LONGEVITY RESEARCH * Single mutants in Caenorhabditis elegans can reduce mortality threefold and combinations of variants lead to as much as a sixfold extension in lifespan, increasing to almost eightfold when combined with dietary restriction. * The first longevity mutant to be identified was the C. elegans gene age- 1 that encodes phosphatidylinositol 3-kinase (PI3K) , which has a key role in a signalling pathway that is homologous to the mammalian insulin–IGF1 (insulin-like growth factor 1) pathway
  23. 23. *The nematode affect mitochondrial function, the so-called Mit mutants. Starting with the identification of clk-1, and now involving about a hundred distinct loci, numerous Mit mutations result in life extension, typically of 20–40% and sometimes more. Many of these mutants interact with the insulin–IGF1 pathway mutants to cause life extension beyond that observed in single-gene mutants alone. *Two key examples are sir-2 and Tor (Target of rapamycin), which were identified in yeast and
  24. 24. Drosophila melanogaster, respectively. sir-2 encodes an NAD-dependent protein deacetylase, which might mediate the lifespan-extending effects of dietary restriction, whereas Tor encodes a protein that is involved in sensing amino-acid availability
  25. 25. * Many candidate genes have been investigated for putative associations with human survival or longevity. Cardiovascular genes * APOE, which is the only gene with common variants that have consistently been associated with longevity, has an important role in regulating lipoproteins * As three isoforms, APOE2, APOE3 and APOE4 * APOE4 has repeatedly been associated with a moderately increased risk of both cardiovascular disease and Alzheimer disease, whereas APOE2 is protective
  26. 26. *In lipoprotein metabolism, microsomal triglyceride transfer protein (MTTP), has also been implicated in human longevity. *Variants in the gene encoding angiotensin Iconverting enzyme (ACE) are also biologically plausible candidates for longevity Metabolism-related genes *Insulin–IGF1 signalling pathway. The presence of at least one copy of a specific IGF1R allele was shown to result in low levels of freeplasma IGF and to be more highly represented among long-lived individuals. The same study also reported that different combinations ofIGF1R and PI3KCB alleles affect free-plasma IGF1 levels and longevity.
  27. 27. * Immune system genes * The multifunctional cytokine interleukin 6 (IL6) is central to this inflammation, and is overexpressed in many of the stress-related conditions that are characteristic features of ageing
  28. 28. * Linkage analysis * Case–control studies * Longitudinal studies
  29. 29. Outlook: the future of human longevity genetics * Although there are many biologically plausible candidates for genes that influence human lifespan, only one finding has so far been replicated * Large-scale and carefully designed studies will be essential for progress in genetic studies of human longevity. Large international collaborations have recently been established in the European Union (the Genetics of Healthy Ageing project GenomEUtwin) and the United States (the Long Life Family Study) to identify genetic and non-genetic factors of importance for exceptional longevity
  30. 30.  These studies assess long-lived siblings and controls, and some of these also include intermediate phenotypes such as cardiovascular risk factors in their offspring.  These studies are most promising when combined with the use of high-throughput genotyping techniques that make multi-locus analysis (of haplotypes and gene–gene interactions) and genomewide association studies feasible. Genome-wide association studies have the advantage that they do not depend on biologically plausible candidate genes or knowledge of specific variants.  Large-scale studies are logistically and financially demanding  Understanding the genetic basis for longevity is an extraordinarily difficult task, but it has the potential to provide insights into central mechanisms of ageing
  31. 31. The record holder of maximum longevity belongs to France's Jeanne Calment,who lived to be 122 years and 164 days old. Longevity ran in her family. Calment's mother lived until she was 86 and her father until he was 94. Her personal outlook of life may also contribute; it is said that she was immune to stress. She was once quoted: "If you can't do anything about it,don’t worry about it”
  32. 32. *"Genes are not destiny!" ~ Bruce Lipton, Ph.D. *The development of an understanding of the true factors of longevity took place so that they may apply them in their lives. *The false belief constantly being expounded by media sources as well as through word of mouth conversations, is disappointing. Longevity genetics are in all of us just waiting to be activated. *It cannot be said that way as "I have longevity genes because my mom lived past the age of 90, so I can eat and do whatever I want." Here we have the entire field of biology which is moving along and making groundbreaking discoveries, yet because of the media's misunderstandings and seemingly western culture's need to avoid taking responsibility, people are not seeing the truth that our health is guided by environmental factors.
  33. 33.  However, we are beginning to see changes. The scientists and academics are beginning to come out with this "new biology" in books and articles geared towards the public.  Also with the advent of quantum physics, its applications to biology on a microcosmic level are just becoming unveiled!  The need to bypass the media with information has become necessary since they've developed ulterior motives and are generally focused on communicating news from a place of fear and dis-empowerment. (For example, the media constantly tries to report on the latest possible cancer "cure" that's just around the corner feeds the public's craving for that onestop-magic-bullet-pill which is never going to exist and stops them from truly taking control of their lifestyle.) The internet is making this very possible. It is no coincidence that time and time again, true progress brings us to a place of empowerment where we can liberate ourselves.  “The true secrets of longevity genetics is in your belief system!”
  34. 34. By: Nazish Nehal, M. Tech (Biotechnology), University School of Biotechnology (USBT), Guru Gobind Singh Indraprastha University, New Delhi (INDIA)

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