Senescence

Gingko Biloba Tree

Senescence is the process of growing old, or aging.  Senescence can refer to a process that occurs on many different levels, from cellular levels, to the whole body level, to higher organizational levels and including physical and psychological structures.

Aging occurs at different rates and different times in different life forms.  Senescence is directly or indirectly a major cause of death.  Senescence may reflect underlying biological processes, mediated by gene expression, can reflect programmed cell death and can be accelerated by environmental factors, such as exposure to radiation.

My 2014 blog article discusses senescence in  the Gingko Biloba Tree, a living fossil dating back to the Permian era (270 million years ago), which exhibits clonal reproduction.  Natural leaf senescence in the Gingko Biloba has been researched in male and female trees, with regards to impacts of reactive species and anti-oxidants on the rates of senescence.

Senescene on a cellular level, expressed as replicative senescence, reflects a cell's attainment of the Hayflick limit.  The Hayflick limit refers to a limit on the shortening of DNA telomeres,  which cap the ends of the DNA strands.  As the cell divides, it loses telomeres in the division process.  The Hayflick limit reflects the end of the telomere line, at which point the cell becomes senescent.  Senescence is accelerated by exposure to reactive oxygen species,  exposure to oncogenes, and to cell to cell fusion, a process where cells join to form what is callled a 'syncytium'.  I discuss a number of the processes that may encourage the early development of senescence in other blog articles, listed below.

Exposure to radiation generates reactive species.  This can include anything from high energy ionizing radiation which liberates electrons from atoms and molecules, to non-ionizing radiation.   Ionizing radiation may include cosmic and gamma rays and some ultraviolet wavelengths.  Geomagnetic storms may result in increased exposure to high energy particles, as would exposure to nuclear radiation.

Non-ionizing radiation includes radar microwaves and those used by cell phones, which can disturb lymphocytes  in rats. Some ultraviolet wavelengths including UVA, UVB and UVC are non-ionizing. Disturbances in the Ozone layer result in increased ultraviolet exposure, with the Antarctic having historically greater ozone depletion than the Arctic. 

 Reactive species can be produced through natural bodily process, in Oxidative Phosphorylation (OXPHOS), in the production of Adenosine Triphosphate (ATP) through mitochondrial processes.  The Metabolic Theory of ecology deals with these issues. It reflects Kleiber's Law which relates metabolism to body weight .  I discuss these issues in my blog on "The Odd Couple - The Mitochondria and the Cell Nucleus", where cellular processes are both exposed to and create oxygen radicals.  This article also discusses other sources of reactive species, including pollutants, chemicals and toxins.

Exposure to oncogenes can also lead to senescense.  Oncogenes can arise from a variety of sources, including potentially avian sources which operate within our body's innate and adaptive immune system transcription factors.

Induction of cell-cell fusion, as occurs in syncytium, can also lead to senescence.  Syncytium can form in protists such as rhizarians, in fungi, in heart muscle and skeletal muscle, and, importantly, in the placenta where they take on a meaning relating to group immunity systems, as discussed in my blog article.  The heart is a critical organ in the human body and tests such as the Cardiac MRI Adenosine Stress Test (using a gadolinium contrast agent) tests the ability of the heart to act "in sync".

 Adenosine is an important nucleoside which modulates a variety of important physiological processes, including heart activity, and as an important moderator of the sleep-wakefulness cycle. Caffeine is an antagonist of adenosine receptors in the brain.  The action of Adenosine is also impacted by theophylline (found in tea) and theobromine (found in chocolate). Adenosine is an inhibitor of the central nervous system and relaxes the heart muscle.  Adenosine also increases hair thickness.  The modulation of adenosine may be related to senescence.

Organismal senescence is a decline in the ability of the organism to respond to stress, and an increase in various symptoms characteristic of aging, including a decline in homeostasis, the ability of the body to respond to various cues.  Alzheimer's Disease is one condition which may be associated with senescence, and may relate to various environmental factors as discussed in my blog article.

Senescence can be mitigated through increased exposure to anti-oxidants, which can be obtained through certain foods (e.g. blueberries are a food high in anti-oxidants),  and internally through transcription factors such as superoxide dismutase.

Senescence may be impacted by a variety of processes germane to environmental issues relating to climate change and global warming, including natural processes and anthropogenic forcing (originating in human activity).  These processes may all impact factors germane to reactive oxygen species and anti-oxidants.

The Odd Couple: The Mitochondria and the Cell Nucleus

Mitochondrion (Creative Image)

Mitochondria are key to understanding many life processes, in the body, in nature,
and in our environment.

Years ago, the Eukaryotic cell   developed as a symbiotic relationship between a prokaryotic cell and a proteobacteria.  The prokaryotic cell may have been an archaea. The proteobacteria was was incorporated into the cell as an endosymbiont.  As gene transfer took place between mitochondrial DNA  and the cell's nuclear DNA, the extent of the  mitochondrial DNA (mtDNA) decreased and the nuclear DNA incorporated more of the functions performed previously by mitochondrial DNA.  As this occured, the relationship changed from being symbiotic to the development of the mitochondrion as an organelle within the cell.

Much of the work developing the theory of symbiogenesis was done by Lynn Margulis in a 1967 paper..  The theory behind symbiogenesis is a very important topic with wide ranging implications due to the complexities involved in the interoperablity of nuclear DNA and mitochondrial DNA.  These issues are ongoing and represent a major challenge in understanding a wide range of scientific issues confronting our society today.

Mitochondria are present in most living cells that include DNA.  Mitochondria are responsible for  a large portion of the energy generated by the cell.  Mitochondria are responsible for the generation of adenosine triphosphate (ATP) from adenosine diphosphate (ADP)  through aerobic processes using its electron transport chain (ETC).  The energy generated as ATP is many times greater than the energy generated through anaerboic glycolysis, which is an energy generation process that does not use oxygen.

The use by the cell of anaerobic  vs aerobic respiration has significance in studying various physiological processes which occur throughout the body.  These issues have implications in wide ranging areas from cancer to the relationship between sleep and wakefulness.

As energy is generated throughout the body, principles of conservation of energy must be satisfied.  Whether energy is generated through aerobic respiration and Oxidative Phosphoylation (OXPHOS)  using the mitochondrial electron transport chain (ETC), energy generation requires inputs and outputs that must be balanced.  This is a principle called "conservation of energy".  OXPHOS generates ATP,  the "energy equivalent of currency" in the body, energy in the form of heat, and outputs such as oxygen radicals (Reactive Oxygen Species (ROS))  as a byproduct of the process.

Oxygen Canisters

Oxygen reactive species such as superoxide (O-), hydrogen peroxide (H202) and the hydroxyl radical (OH-) can be generated depending upon a number of factors.   This includes natural process in the body involving signaling and homeostasis and also exposure to a number of environmental factors which may increase their generation.  Antioxidants may help the cell counter some of the impacts of reactive species.

Exposure to pollution, chemicals, toxins and radiation may increase oxygen reactive species exposure.  Radiation exposure may include ionizing radiation or non-ionizing radiation  such as cosmic rays  (e.g. gamma rays ).  Geomagnetic storms  and reduced ozone layer  protection at polar regions as Antarctica and the Arctic may increase such exposure, with greater historical ozone depletion  over the Antarctic.

I photographed in Antarctica in November/December 2004, and in October 2006 and photographed in the Arctic in July 2005.  The year 2006 saw the worst levels of depletion (2004 Image-Halley Bay Station, Antarctica) in recorded history.

Cellular processes guide apoptosis, or programmed cell death under a number of circumstances, generating  an intrinsic pathway or extrinsic pathway for cell death.  Reactive species play key roles in this process, as signaling mechanisms, and also in promoting cell death, as free radicals generated by a variety of situations trigger apoptosis.

Mitochondria play a large role in enforcing 'group identity' in a cell. The mitochondria helps to sustain certain energy needs within the body and when certain system parameters (group identity system requirements) are not fulfilled, the process of apoptosis or programmed cell death is intended to kill off certain cells that do not meet those system parameters.

Mitochondria can be loosely or tightly coupled; this means that they can "leak" protons so that more heat is produced (uncoupled) relative to amount of ATP produced;  there are certain uncoupling proteins  that aid in this process, which decreases  the generation of potentially damaging oxygen radicals.  A highly coupled system will thus be more efficient in the generation of energy, less efficient in generating heat, and will generate more oxygen radicals, which can cause damage to the system.  A more loosely coupled system will produce more heat, will generate less oxygen radicals, and will be less efficient in generating energy.  A loosely coupled system will be more valuable in colder climates due to the greater heat protection.  A tightly coupled one will result in more conditions, such as diabetes, which are impacted by the generation of oxygen reactive species.

The generation of reactive oxygen species is a significant issue in DNA damage  and mutations involving mutagenesis.  Mitochondrial DNA (mtDNA) are much less protected from the generation of reactive species than nuclear DNA.  In the proverbial sense, they sit at the edge of the  oxidative phosphorylation 'fiery furnace' and absorb more damage than nuclear DNA.  Nuclear DNA has greater protection from reactive species, being protected by histones   and telomeres.

Mitochondria can be damaged by reactive species, however, there is a certain amount of punishment that mitochondria can take before a process called heteroplasmy  takes place. Heteroplasmy in the mitochondria is a process where, due to mutation, mitochondrial damage or other process, more than one mitochondrial genome can exist.  This process may be associated with mitochondrial disease and be more extensive the greater the degree of heteroplasmy.  However some individuals may live to long ages with some degree of heteroplasmy.

There is a basic problem with mitochondrial damage and mutation in so far as the mtDNA and the nuclear DNA interoperate in the OXPHOS process.  This is because, as mentioned earlier in the article, some mitochondrial functions ages ago were shifted into the nuclear DNA through the process of gene transfer.  Cytochrome C belongs to the cytochrome c family of proteins and is an integral part of the ETC.  Cytochrome C has a long history, which goes back to time periods when the Earth was subject to heavy amounts of radiation.  Illnesses associated with Cytochrome C may involve both nuclear DNA and mitochondrial DNA.

Since Nuclear DNA has greater protection than mitochondrial DNA (mtDNA) from the insult of reactive species, the degree of damage in each case will differ, or in the case of nuclear DNA, there may be minimal or no damage.  This will lead to interoperability issues as mutations and damage occurs. Interoperability is the ability of systems to work together.  As oxidative stress occurs at different rates and to different but  inter-operating parts of the cell (mtDNA and nuclear DNA), illness and damage occurs, and potentially mutations.  This occurs in systems requiring heavier use of energy, including muscles.  Respiratory muscles bear the burden of oxidative stress, as these muscles are those subject to the greatest use during sleep.  Sleep apnea may be associated with higher levels of exposure to oxidative stress.

As we are subject to greater and greater levels of substances that create oxygen reactive species, we can see that problems can add up.  There are greater and greater chances of damage and mutations, the probability of heteroplasmy increases, the levels of heteroplasmy in the cell may come closer to the levels of heteroplasmy that may be tolerated in the cell without incurring mitochondrial disease.

We can see, therefore, that exposure to reactive species such as environmental toxins and radiation may provide for mutations in both nuclear and mitochondrial DNA, that these processes may occur at different rates, and that past a certain point, mitochondrial disorders may develop as the result of such exposure. At the same time, mutations that are beneficial may sometimes occur, and mutations and damage that are harmful may indeed result.  The ability for mutations that are adaptive to occur may reflect the ability of the mitochondrial DNA and the nuclear DNA to inter-operate, which is statistically difficult, considering the conditions under which each of these processes work.

Thus any process which seeks to advance a species by introducing mutagenic factors via the use of the creation of oxygen radicals must take into consideration that mutations and damage may result in the process and that individuals may be harmed in such process.  Due consideration must exist for who is subject to such exposure, and when the risk of subjecting certain individuals to such exposure constitutes a material risk that makes such experimentation untenable in  a civilized society.

 The risks of exposure to reactive species increases with the degree and length of the exposure, impacting the risk of early morbidity and mortality. Mutagenesis is more effective when it occurs in germ line cells which can pass mutations, either favorable, or unfavorable on to the next generation

Where such experiments are conducted, they must be conducted in an ethical fashion, they must be done with full informed consent of those involved, they must adhere to the law of civilized nations, and the ongoing experience of such studies must be monitored and measured so that those involved are not unduly harmed and the patient population put at excessive risk.

It must be made abundantly clear that if our society depends upon mutations to adapt the species to future environmental (or other) challenges, that those who have been subject to environmental (or other) assaults for such purpose be treated with due respect, that their contributions be valued, and their condition be measured, monitored and treated. It is clear that what these individuals are doing on a collective basis is aiding the future development of humanity. They are test subjects in a process that will benefit others, later.

What are our future ecological and planetary challenges and how can we adapt to them?  How do these challenges impact our exposure to environment risks and how we deal with them?  These are all important issues.

The mitochondria, as a vital cog in the production of energy has a very important part of the story that must be told as we seek to deal with the environment, climate change and other planetary challenges that we face.