This is a relatively old theory yet science is bringing it back to the headlines. In contrast to other theories of aging, which are based on accumulation of damage or gradual degeneration of cells in the body, this theory establishes evidence of a programmed death. There are solid supporting facts to this classical theory, like the famous Darwinian theory of evolution. The latter depicts that survival of a species is only needed up to a point where reproduction has been completed and the offspring has fully acquired a level of independence. It is a raw fact that youngsters are more prominent players than the old, putting it directly and crudely, young species need to survive while it is best to dispose the less important ones (old). Freedom must be given to the young species so that competition amidst old and young does not start avoiding fierce-full fights putting one against the other for the struggle of survival and infinite resource.
The derived conclusion is that evolution does eventually set a peak; a limit to life span, so that the older of any species die off to leave the deck clear for younger generations to proliferate. Death is not necessarily caused by accumulation of damage according to this theory but rather to a pre-defined/programmed death. Research in this particular theory “programmed epigenomic changes” stopped at this point and remained uncovered due to impossibility to prove that there were any biological evidences that could prove this programmed aging and death. However, impossibility has been turned into possibility with advancement in technology and the introduction of gene chips and computational genetics. Research in genetics is already generating proof of the theory.
One of the first theories of aging that supported the fact that aging was programmed is ‘telomere shortening theory’. In 1990s, the theory surfaced, the mechanism of programmed age in this theory is simple. Telomere shortening in somatic cells makes the cell division process numbered. At a peak, genomic replication of somatic cells becomes instable, as cell turns fragile. This is how the death is genetically programmed.
Recent research in computational genetics has showed that there is a multiplicity of switching mechanism in our genes that actually might program our death. There are many genes involved in the so-called aging process. In the process, there might be one as well as many master programs that make genes switch off and on. This produces the various phases of our lifetime, growth, maturity and decline stage to death.
Epigenomics deals with providing a framework that clarifies the aging process as being a programmed event. Heritable as well as non-heritable alteration in gene expression is scrutinized in epigenetics. Facts are derived from the life-occurrence of cells kept in histone actylation patterns and DNA methylation that accumulates as the cell division continues. This type of study is called epigenetics and is concerned with analyzing single genes as well as a set of genes. Epigenomics is the study of alteration in the whole genome thus including epigenetics. It is, hence, a study of genetic changes that constantly evolve during the lifetime of organisms and thereby demarking the aging process.
NF-KappaB signaling is an important chapter in epigenomic research. It is nuclear transcription factor, which is responsible for cell communication. In many cells, NF-KappaB is latent (inactivated). One of the positive aspects of NF-KappaB is that it acts as a body control mechanism to deal with stress, damages, cancer and various diseases. For instance, NF-kB is a necessary gene in eukaryotic cells as it assures cell proliferation as well as survival. It appears to have anti-apoptotic genes, which protects cells from dying. However, on the negative aspect, NF-kB association to gene is known to cause negative inflammation impact as well as oxidative damage. The fact that it frees radicals causes changes to NF-KappaB in cells such as cytoplasm and thereby triggering inflammatory outcomes which are common. For example, metastasis, angiogenesis, invasiveness and proliferation in autoimmune disease, neurodegenerative diseases and cancer tumor are all possible outcomes as well as encouraging human immunodeficiency virus (HIV) which can turn into AIDS.
Hence, blocking NF-kB can be a possible mechanism to improve the health of people as it will help to tackle cancer, inflammatory problems, neurodegenerative problems, Parkinson’s Disease as well as AIDS.
Going back to programming of aging, research is categorizing NF-kB as being associated to longevity. A recent research reveals that aging of various tissues such as kidney, fibroblasts, skin, cortex, abdominal muscle, brain, and muscle amidst other can be reversed by inhibiting NF-kB cell signaling. Blocking of NF-kB enabled epidermal tissues to rejuvenate based on a research carried out on old mice, which had their tissues back to the state of a young mouse. NF-kB according to the author of the research concluded that the signaling tends to influence age of nine other cell types and that human beings might have their tissues rejuvenated.
According to a fresh and topical analysis, Tumor Necrosis Factor (TNF) instigates NF-kappaB in Muscle Progenitor Cells (MPC). This analysis correlates with the 13th theory of aging, Deterioration of the Stem Cell Supply Chain. TNF functions through various channels in a complex way, involving commencement of NF-kappaB, to generate numerous effects such as stimulation of apoptosis (cell suicide). Apoptosis is advantageous in cases of cancers. However, it can be harmful to vigorous cells. In Muscle Progenitor Cells, TNF-alpha may initiate NF-kappaB in animals which are older rather than younger. Eventually, TNF onset of NF-kappaB in older animals can cause apoptosis and hence death of strong MPC. Nevertheless, there are appropriate diets to control NF-kappaB.
Further study has shown that sirtuin protein SIRT6 is crucial in diminishing the start of NF-kappaB and therefore delaying aging.
All these studies thereby indicate that aging is planned instead of being the consequence of accrued destruction and that this program may be inverted.
Protecting or Firewall against Programmed Epigenomic Changes
1. Lifestyle
There isn’t any specifically prescribed lifestyle to avoid programmed epigenomic change. However, if some possible approaches are present try the lifestyle guide of
Oxidative stress or any other theories found on ‘A Road Map to Anti-Aging Theories”
2. Medical Supplement or Firewalls against Programmed Epigenomic Changes
One of the causes of Programmed Epigenomic changes is telomere shortening; hence, a comprehensive firewall is established on “telomere shortening and Damage”.
The other cause of programmed epigenomic changes is through inhibiting NF-KappaB. There are many strong supplements that blocks NF-KappaB cell signaling. A list of 39 substances that have different effects in the blocking of NF-kappaB binding activity are:
1. Resveratrol
2. Pycnogenol
3. Curcumin
4. Green tea
5. Ashwagandha
6. Astragalus
7. Astragaloside IV
8. Gingo biloba extract
9. Vitamin C
10. Boswellia
11. Allicin
12. Alpha-lipoic acid
13. Vitamin E
14. Vitamin D-3
15. Vitamin B-6
16. Folic acid
17. Grape seed extract
18. Avena sativa
19. Co-enzyme Q-10
20. EPA
21. DHA
22. Carnosine
23. Lycopene
24. Magnesium
25. Melatonin
26. Quercetin
27. Blueberries (as well as some other berries)
28. Ginger
29. Dark chocolate
30. DHEA
31. Bilberry extract
32. Stinging nettle
33. Grape seed extract
34. Glucosamine
35. Benfotiamine
36. Acetyl-l-carnitine
37. Potassium
38. Vitamin B-12 (cobalamin)
39. Pantothenic acid
There are still more that can be mentioned. Antioxidants and firewalls that are effective in the various anti-aging theories do also work well in preventing the expression of NF-KappaB. To understand the mechanism, it is important to know that cytoplasm of cells contains a large amount of NF-kappaB. However, it is concealed (kept in custody) by a type proteins in the IkB family. Yet, free radicals (reactive oxygen species) cause NF-KappaB to be released and thereby a translocation process occurs where it reaches the nucleus of the cell. Having reached the nucleus it fastens and affects various genes causing depriving effects such as oncogenesis (malignant transformation causing cancer) inflammation. The antioxidants diminish the risk of free radicals and consequently NF-KappaB is blocked.
Some other effect of the 39 substances is to act through suppression of IL-1Beta, TNF-alpha and IL-6 has distinct features such as motivating cancer cells to commit apoptosis. For instance, Ginko Biloba, Curcumin and Resveratrol tend to promote differentiation, telomerase enzyme and proliferation of some progenitor cell and somatic stem types through a P13/Akt, a particular pathway. Moreover, degenerative bone disease like osteoclastogenesis, rheumatoid arthritis and osteomyelitis can also be addressed with Curcumin and Resvertrol.
Recent research which showed that inhibiting NF-KappaB cell signaling could reverse age of tissues for mouse brings us to another level. If ever applicable to human then this firewall can appear of paramount importance. It can go ahead of age control to reverse the age of organs and make ‘people’ young again.
Research is required in the field of NF-KappaB
Controversially, facts are still unclear about NF-KappaB in correlation to neurogenesis. There are two opposing schools of science.
One considered that the firewalls that generate neurogenesis like curcumin, resveratrol, DHEA, EPA and DHA fish oil and pregnenalone does tend to block the NF-KappaB. This is considered as a necessary process to allow neurogenesis.
Yet, many published articles listed below predict the contrary.
1. Potential role of NF-kappaB in adult neural stem cells: the underrated steersman?
2. Enhancement of hippocampal neurogenesis by lithium.
3. Fluoxetine targets early progenitor cells in the adult brain
4. Lithium induces NF-kappa B activation and interleukin-8 production in human intestinal epithelial cells.
5. Fluoxetine increases the nitric oxide production via nuclear factor kappa B-mediated pathway in BV2 murine microglial cells.
They say that activation of NF-kB is vital for neurogenesis as it might have a prominent signaling pathway. For instance, two anti-depressants Fluoxetine and Lithium do both activate NF-KappaB as well neurogenesis. Moreover, animal research proves that that neural progenitor cells is effective in generating proliferation of cells as NF-kB is activated. Adult neural stem cells are proliferated once NF-kB is activated with Tumor Necrosis Factor Alpha. Apparently there are many NF-kappaB proteins and that might account for the differential interaction.
Considering an alternative justification, maybe firewall substances (antioxidants) have an outcome that actually outweighs the blocking of NF-KappaB associated with neurogenesis benefits. As it can be noticed, the transduction factor is highly complicated and NF-kappaB role in longevity research remains a question to be discovered.
Reference:
1. Anti- aging firewalls the science and technology of longevity.
Further Reading and Forum Discussion on NF-KappaB
Anti Aging Supplements, Anti Aging Theories, Health And Aging, Longevity
Wed, Dec 23, 2009
Anti Aging Supplements, Anti Aging Theories, Health And Aging, Longevity