Contributor

  Autophagy - Reutilization recovering 70% of our proteins.


D. S. McGerk | August/2017


The Heart's Electrical System and Abnormal Rhythms and human longevity.

Topic: Autophagy - a New Science

Animal adaptation to Food Shortages

which for the last 30 years has been developing. Professor Yoshinori Ohsumi pioneered this new science base on the work of other Nobel Prize winners on Liposomes/Vacuolar System and the Ubiquitin/Proteasome System. The trail to cellular recycling of Scarce Resource was being uncovered. When we consider that the normal state of man throughout evolution was Starvation, this implies that Fasting is a Normal State, then Eating is a Stress State. (1,1a,b,c) (Note 1)

During starvation periods and lack of carbohydrate sources (seasonal), the formation of ketone bodies increases dramatically. Prolonged low levels of insulin result in both increased fatty acid release from adipose tissue, and increased amounts of the enzymes required to synthesize and utilize ketone bodies. Ketone fuel is more efficient and has less waste by products. Animals store and they do not store , except for a limited . In addition, it turns out we have a for protein recovery as micro-molecules and metabolites. (2,3,3a)

 

Proteins How Much | What should be dietary goals?

The last 30 years of the development of the science of autophagy, has shown the efficacy of animal metabolism to recover and utilize Scarce Resources. The graph presented shows Prof. Ohsumi's analysis of protein reutilization and it is about 70% efficient since some damaged and folded proteins cannot be recovered. (Note 3, Summary)

In the mid 1950's scientists observed a new specialized cellular compartment, called an organelle, containing enzymes that digest proteins, carbohydrates and lipids. This specialized compartment is referred to as a "lysosome" [Nobel Prize, Christian de Duve] and functions as a workstation for degradation of cellular constituents. Christian de Duve coined the term Autophagy - Self-eating. The new vesicles were named autophagosomes. (4)

Dr. Ohsumi found that autophagy is essential to maintaining vital activities in the body as it recycles amino acids that are the building blocks for proteins inside the cell. It is thought that a malfunction with autophagy is a factor in disorders such as Parkinson's disease, and scientists are hoping that this research will lead to the development of preventative measures and new treatment methods.

 

Autophagy | A Process of Cellular Digestion and Recycling

Dr. Patrick's Interview about Autophagy with

Dr. Guido Kroemer on Autophagy, Caloric Restriction Mimetics, Fasting & Protein Acetylation - Jul/2017.

FoundMyFitness.com - Dr. Rhonda Patrick

is an evolutionally conserved intracellular process to maintain cellular homeostasis by facilitating the turnover of protein aggregates, cellular debris, and damaged organelles. It is a process whereby cellular activity sequesters portions of the cell and digesting them. (5) This recycling takes this cellular material and degrades the macromolecules into micro-molecules and metabolites. This is part of the cell's Repair and Maintenance cycle.

Most readers understand Apoptosis which is cell death, and a programmed mechanism, but Autophagy and apoptosis work together to control the turnover of organelles and proteins within cells. This Self-consumption of cells and cellular materials is an animal adaptation for capturing and reusing scarce resource. (6) However, these two process are distinct self-destructive processes in that Apoptosis, Self-killing and the other Autophagy, Self-eating.

Autophagy, the human body's reutilization of proteins amino acids and micronutrients with a 70% efficiency, conservation of scarce resources.
Fig 2: From Dr. Ohsumi's Nobel Prize acceptance speech (1) - Autophagy and Reutilization of Protein amino acids. This science has now been connected to various physiological cellular functions (.ppt presentation - 70GoingOn100.)

| Open diagram in new window |

This new science has gone from 20 published papers 30 years ago to over 7,000 last year alone. The two processes of Autophagy and Apoptosis regulate cell death and cell recycling and seem to work in conjunction with cellular stress and aging. Accumulation of intracellular damage is an almost universal Hallmark of Aging. An improved understanding of the systems that contribute to cellular protein quality control has shed light on the reasons for the increased vulnerability of the proteome to stress in aging cells. Maintenance of protein homeostasis, or proteostasis, is attained through precisely coordinated systems that rapidly correct unwanted proteomic changes. (7,8,8a,9) (Note 4, 5)

 

Autophagy and Aging | Declining autophagy Efficiency?

at last a primary focus of 70 Going On 100 and living to 100, i.e becoming a Centenarian. Dr. Yen and Dr. Klionsky explain that autophagy is involved in aging ... For example, the role of various hormones and nutrient sensing pathways in life span extension may involve autophagy. Similarly, autophagy is the primary mechanism for removing damaged organelles, such as mitochondria, which may have a direct impact on aging. Autophagy, an evolutionarily conserved catabolic pathway in eukaryotic cells, plays an important role in stress response and the degradation of damaged cytosolic components. (10,11)

According to Dr.'s Yen and Klionsky - [How to Live Long and Prosper: Autophagy, Mitochondria, and Aging] (10) - Aging cells gradually accumulate various deleterious changes, resulting in a decline in cellular function and eventually leading to cell death and disease. The accumulation of damaged macromolecules and organelles is one of the most persistent changes in aging cells and is associated with the decline of different catabolic pathways. Autophagy deficiency during aging has been proposed to be the main cause of this biological waste accumulation. (12,13,14)

Autophagy and reutilization of protein and living to 100 or past 100

A prominent theory of aging holds that decaying of mitochondria, Mitochondrial Dysfunction Dr. Mercola and Dr. Patrick | jan/2016, (15,15a,b) is a key driver of aging. While it's not clear why our mitochondria fade as we age, evidence suggests that it leads to everything from heart failure to neurodegeneration. DNA repair is the issue. Refs ... DNA - Repair, PubMed.

is generally activated by conditions of nutrient deprivation but has also been associated with physiological as well as pathological processes such as development, differentiation, neurodegenerative diseases, stress, infection, and cancer. mTOR is a critical regulator of autophagy induction, with activated mTOR suppressing autophagy, and negative regulation of mTOR promoting it. Autophagy biological activities of senescence cells. Autophagy provides energy through the turnover of intracellular proteins and organelles to guarantee rejuvenation and adaptation in various conditions. (16)

, autophagy functions as a pro-survival mechanism; however, excessive autophagy may lead to cell death, a process morphologically distinct from apoptosis. The accumulation of damaged macromolecules and organelles during aging occurs due to reduced autophagy activity and leads to reduced lifespan, (17) i.e. we do not want junk and senescent cells collecting, re-cycling is needed. (18)
Example: we replace all blood cells, on average, every115 days (3 times/yr), that is approximately 300,000,000,000 (billion cells per day), - ref ... this site - Healthy Heart and Longevity.

is a form of Dieting and Stress on our bodies which everyone does intentionally or unintentionally. If we are not aware of our nutrition we will trigger Dr. Ames' Triage Theory and our body will start to reallocate nutrients in favor of short term health. (Example: it has been shown that Vitamin K goes to blood clotting first, before it is used in other enzymatic functions such as clearing calcification of arteries.)

, was partially right, as low carbohydrates (CHO) is the best way to eat to avoid the complications of Insulin Resistance and Chronic Inflammation. However, Atkins did not understand the importance of controlling Proteins (Autophagy - Reutilization), and hence because of the Fear of Fat, people replaced carbs with proteins.

Controlling Human Growth hormones and mtor protein pathway and living to 100
Shomu's Biology videos, 2015.

| Open diagram in new window |

, in cells since it is a missing nutrient. [Sabatini, 2016] It has been shown that after the age of about 30, insulin becomes less of a growth factor and the protein “Leucine” (a Branch Chain Amino Acit - BCAA) becomes the control. [Dr. Layman, 2013 - Protein Balance] (Note 6)

is a part of the survival pathway of cell signaling that helps in cell growth and proliferation. It is the central component of a nutrient and hormone sensitive signaling pathway that regulates cell growth and proliferation. This pathway becomes deregulated in many human cancers and plays an important role in the control of metabolism and aging. (19,19a)

The cell has to sense the proper nutrient levels for growth, both macro and micro nutrients. The mTOR and IGF are primary growth regulating pathways. Dr. David Sabatini a leading researcher on growth pathways such as mTOR provides an - Advanced Lecture: Regulation of growth by the mTOR pathway | Dr. Sabatini Lecture Series, march/2013 and a follow up in 2016 with David Sabatini, PhD , MD , Growth By The mTOR Pathway | cell signaling technology inc, feb/2016

The most powerful stimulation of mTOR is excess proteins. The best drug to reduce to "Slow Aging" and the chronic diseases associated with it, is already available … Avoid High Proteins!

 

 


  1. Autophagy and Apoptosis fail to regenerate defective cells and reutilize proteins and rebuild cells. Key Knowledge: You are turning off your immune system with a poor diet. The body favors short-term survival over long-term health. This trade-off accelerates aging-associated diseases, such as cancer, cardiovascular disease, immune dysfunction, and cognitive decline.

    High carbohydrate diets, that are also high in omega-6 fats, shut down and confuse the body’s own antioxidant defense genes which are far more powerful than any supplement you can take. Unrecognizble free radicals are created.

    ... Fats, ... Carbs, ... Ames - Triage Theory.

  2. One of the is protein control in that it recommends a medium intake. Dr. Ohsumi's work indicated this parameter is in balance with animal adaptations. Protein restriction is also a component of Dr. Longo's FMD - Fasting Mimicking Diet. His proposed prolonged fasting (5 days) should limit proteins below 10% of caloric intake, and increase carbohydrates. This falls in line with the Cycle-In-Out of mode as suggested by Dr.'s Mercola, Pompa, and others. Staying in Fat-burning mode, i.e. running on ketones, does not need to be done at full time once you are Fat-Adapted.
  3. is we put Excess Proteins Consumption in the same category as Excess Carbohydrates both place undue burden on our metabolism. (Note 1,2) Will we ever find that happy balance? Our metabolic pathways are always dynamic pathways, and rely on a minimum required amount of macro and micro nutrients, consequently, our cells have developed a mechanism for conserving scarce resources, since historical evidence shows that Starvation/Fasting was the Normal State of Humans.

 

 

Notes:

  1. Professor Ohsumi's discoveries led to a new paradigm in our understanding of how the cell recycles its content. His discoveries opened the path to understanding the fundamental importance of autophagy in many physiological processes, such as in the adaptation to starvation or response to infection. Mutations in autophagy genes can cause disease, and the autophagic process is involved in several conditions including cancer and neurological disease. Built upon the work of The Nobel Prize in Chemistry 2003, Peter Agre, Roderick MacKinnon.. The Nobel Prize in Chemistry 2004, Aaron Ciechanover, Avram Hershko, Irwin Rose. (1,1a,b,c,d)
  2. The kidney is an ingenious apparatus for removing substances the body wishes to dispose of. In its windings (termed glomeruli), which function as a sieve, water, ions and other small molecules leave the blood as ‘primary’ urine. Over 24 hours, about 170 liters of primary urine is produced. Most of this is reabsorbed with a series of cunning mechanisms so that finally about one liter of urine a day leaves the body. (20)
  3. The word autophagy originates from the Greek words auto-, meaning "self", and phagein, meaning "to eat". Thus, autophagy denotes "self-eating". This concept emerged during the 1960's, when researchers first observed that the cell could destroy its own contents by enclosing it in membranes, forming sack-like vesicles that were transported to a recycling compartment, called the lysosome, for degradation. In a series of brilliant experiments in the early 1990's, Yoshinori Ohsumi used baker's yeast to identify genes essential for autophagy. He then went on to elucidate the underlying mechanisms for autophagy in yeast and showed that similar sophisticated machinery is used in our cells.
  4. - There is accumulating evidence that ageing / aging, is associated with a progressive dysfunction of autophagy, a condition that may favor the accumulation of dysfunctional mitochondria, nuclear genome instability, stem cell attrition, enhanced loss of post-mitotic cells, immunosenescence, unwarranted inflammatory reactions and, in the end, the reduction of hormetic responses that is required for the adaptation to stressful conditions. Moreover, autophagy is induced by, and required for, the positive influences of longevity-extending regimens, including caloric restriction, inhibition of insulin and insulin-like growth factor signaling (IGF-1, IGF-2, IGFs, GH Axis), (21,22) [Wikipedia
  5. Protein function is generated and maintained by the proteostasis network (PN) (Balch et al. (2008) Science, 319:916). The PN is a modular, yet integrated system unique to each cell type that is sensitive to signaling pathways that direct development and aging, and respond to folding stress. Mismanagement of protein folding and function triggered by genetic, epigenetic and environmental causes poses a major challenge to .
  6. While most amino acids are broken down in your liver, BCAAs are broken down primarily in your muscle. As such, they're believed to help improve exercise performance as well as reduce the breakdown of muscle. Exercise and Gene Expression
    Three amino acids - leucine, isoleucine and valine, are considered branched-chain amino acids (BCAA) because they have a branched molecular structure. In particular, leucine is shown to "accelerate recovery from muscle damage by preventing excessive inflammation". (23,24) We discuss leucine as a factor in Protein Balance and Metabolism.
living to 100
VA Pittsburgh Healthcare System
Curbing Cancer's Sweet Tooth

Dr. Tan is introducing Veterans with advanced cancer to a ketogenic LCHF - (high-fat, adequate-protein, low-carbohydrate) diet. This eating plan starves cancer cells while still meeting a patient's nutritional needs.

Take Action
Enhancing hero-worthy care for
Our Nation's Veterans.

[ + ] Sources and References:

  1. DNA Repair PUBMED, NCBI, PUBMED, Effects of micronutrients on DNA repair. Collins AR, Azqueta A, Langie SA.
  2. 1 youTube acceptance speech, Nobel lecture: Yoshinori Ohsumi, Nobel Laureate in Physiology or Medicine 2016
  3. 1a Nobelprize.org, the 2016 Nobel Prize in Physiology or Medicine, Yoshinori Ohsumi for his discoveries of mechanisms for autophagy
  4. 1b Nobelprize.org, The Nobel Prize in Chemistry 2003, Peter Agre, Roderick MacKinnon.
  5. 1c Nobelprize.org, Proteins labelled for destruction, The Nobel Prize in Chemistry 2004, Aaron Ciechanover, Avram Hershko, Irwin Rose.
  6. 1d Nature - Cell Biology, Nature Cell Biology 6, 1011 (2004), doi:10.1038/ncb1104-1011, A prize for protein degradation, Hershko, Ciechanover, Rose.
  7. 2 Rose Hulman edu, The Synthesis and Utilization of Ketone bodies, Copyright 2000-2003 Mark Brandt, Ph.D.
  8. 3 Cell Press, 2016 Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan, Valter D. Longo and Satchidananda Panda
  9. 3a Cell Metabolism, Jun/2016, Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan, Valter D. Longo, Satchidananda Panda
  10. 4 Nobelperize.org, The Nobel Prize in Physiology or Medicine 1974, Albert Claude, Christian de Duve, George E. Palade
  11. 5 APS - American Physiological Society, Autophagy: a potential therapeutic target in lung diseases, Kiichi Nakahira, Augustine M. K. Choi
  12. 6 NCBI PMC, Self-consumption: the interplay of autophagy and apoptosis, Guillermo Mariño, Mireia Niso-Santano, Eric H. Baehrecke, and Guido Kroemer.
  13. 7 NCBI PubMed, The role of protein clearance mechanisms in organismal ageing and age-related diseases. Vilchez D, Saez I, Dillin A.
  14. 8 NCBI PubMed, Modeling general proteostasis: proteome balance in health and disease. Roth DM, Balch W.
  15. 8a Science Direct, Elsevier, Modeling general proteostasis: proteome balance in health and disease, Daniela M Roth. William E Balc.
  16. 9 NCBI PubMed, The biology of proteostasis in aging and disease. Labbadia J, Morimoto R.
  17. 10 American Physiological Society, 2008, How to Live Long and Prosper: Autophagy, Mitochondria, and Aging. Wei-Lien Yen, Daniel J. Klionsky
  18. 11 Science.org, 2000, Autophagy as a Regulated Pathway of Cellular Degradation, Daniel J. Klionsky, Scott D. Emr.
  19. 12 NCBI PubMed, 2004, Myocyte aging and mitochondrial turnover. Terman A1, Brunk UT.
  20. 13 NCBI PubMed, 2005, Autophagy and aging: the importance of maintaining "clean" cells. Cuervo AM, Bergamini E, Brunk UT, Dröge W, Ffrench M, Terman A.
  21. 14 Science.org, 2003, Autophagy Genes Are Essential for Dauer Development and Life-Span Extension in C. elegans. Alicia Meléndez, Zsolt Tallóczy, Matthew Seaman, Eeva-Liisa Eskelinen, David H. Hall, Beth Levine.
  22. 15 AJHG, Cell.com Mitochondrial Chemical Biology: New Probes Elucidate the Secrets of the Powerhouse of the Cell, Simon Wisnovsky, Eric K. Lei, Sae Rin Jean, Shana O. Kelley.
  23. 15a ScienceDirect, V1823:12, 201, Mitophagy is triggered by mild oxidative stress in a mitochondrial fission dependent manner, Magdalena Franka, et al.
  24. 15b Dr. Mercola.com, How Your Mitochondria Influence Your Health, January 24, 2016
  25. 16 Cell Signaling Technology, Autophagy Signaling Pathway
  26. 17 NCBI PMC, Overexpression of Atg5 in mice activates autophagy and extends lifespan, Jong-Ok Pyo, et al.
  27. 18 JBC - Journal of Cell Biology, 2011 192:4, Four faces of cellular senescence, Francis Rodier, Judith Campisi
  28. 19 Hournal of Cell Science, 2009 mTOR signaling at a glance, Mathieu Laplante, David M. Sabatini
  29. 19a youTube, mtor signaling pathway
  30. 20 Nobel Prize .org, Oct, 2003 - Nobel Laureates Peter Agre and Roderick MacKinnon, Molecular water channels through the cell wall.
  31. 21 NCBI PubMed, The hallmarks of aging. López-Otín, Blasco MA, Partridge L, Serrano M, Kroemer G.
  32. 22 Encyclopaedia Britaninica, Insulin-like growth factor (IGF), BIOCHEMISTRY, by: Robert D. Utiger.
  33. 23 NCBI PubMed Amino Acids. 2016 Sep;48(9):2145-55. doi: 10.1007/s00726-016-2240-1. Leucine-enriched essential amino acids attenuate inflammation in rat muscle and enhance muscle repair after eccentric contraction. Kato H, Miura K, Nakano S, Suzuki K, Bannai M, Inoue Y.
  34. 24 Healthy Eating, Do You Need to Eat Essential Amino Acids Every Day? by Melodie Anne , Demand Media

About Us

is a positive online community for seniors who are interested in longevity and becoming centenarians. Living to 100 years of age becomes a goal, and sharing and exploring this goal is an issue that matters to those in the golden years. A platform for the energetic, creative, and productive, to share life experiences by contributing your experiences on this site. Founded to explore quality living, healthy aging, longevity and becoming Centenarians.