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.

Evolution of Adaptive Immunity

Two Trees (creative digital image)

I attended a "Weiser Endowed Lecture in Immunology" featuring Dr Max Cooper of the Emory University School of Medicine, speaking on "Evolution of adaptive immunity" at the University of Washington in 2012.  Dr Cooper's work is foundational in this subject area.

It is interesting that immunity systems follow a phylogenetic pathway much as the phylogeny of species themselves do. The evolutionary pathway of jawless vertebrates (of whom hagfish and lampreys are surviving members), possess differences in comparison to the common evolutionary pathway followed by other vertebrates.

Lampreys and hagfish do not possess a thymus , nor do they possess a spleen.    Lampreys and hagfish do not possess Major Histocompatibility Complex (MHC) 1 or 2, T-cell receptors or recombination activating genes (RAG 1 and 2) which play an active role in the recombination of T-cell and immunoglobulin  receptors. Lampreys and hagfish posses hematopoietic tissue, the former in the intestine and the latter in the portal vein.  With these changes, the lampreys and hagfish diverged off the common immune system evolutionary pathway prior to the development of certain MHC class immunity in other species.  This is an important benchmark due to the major role that the MHC class plays in vertebrates.  It is a vital aspect which makes the concept of a separate phylogenetic pathway earmarked for the immune system so interesting.  If lampreys do not possess a thymus, then what substitutes in its place?

Lampreys and hagfish utilize a system of leucine-rich repeats )(LRR's) to mediate immune system responses using Variable Lymphocyte Receptor (VLRs), (VLRA's, VLRB's and VLRC's).  The interesting aspect of the jawless vertebrate immune system function is comparing its action in structure and function to the immune systems we are familiar with.  VLRB's have structures similar to toll like receptors (proteins that play a key role in the innate immune system), while their functions are similar to those of antibodies,  and they possess humoral characteristics (using macromolecules in extracellular fluids in immunity systems). They act using discrete populations of lymphocytes (types of white blood cells) .

VLRBs act as an adaptive immune system and can differentiate foreign from self in recognizing lymphocytes.

Lampreys posses a diverse variety of leucine-rich repeats which code for germline and mature genes. They possess a specificity for carbohydrate and protein receptors on bacterial and mammalian cells. They bind antigens with high avidity and affinity, describing the binding capacity of multiple versus single interactions of antibodies with antigenic epitopes.

 In "Evolutionary implications of a third lymphocyte lineage in lamprey", the authors find a thymoid source for VLRA and VLRC assembly in the lamprey gill tips, while VLRB assembly occurs in hematopoietic typhosole and kidney tissues.  VLRC appeared more numerous than VLRA, and predominated in the skin.  They conclude that a similar body plan of two T-cell type lymphocytes in a thymoid type structure and one B-cell type lymphocyte in the blood and kidneys shows some similarity in basic structure to the immune system for jawed vertebrate, while achieving adaptive immunity through different means.

Monclonal VLRB antibodies  from immunized lamprey larvae can recognize plasma cells from myeloma patients.  VLR4, a monoclonal VLRB specific for BclA, the bacillus collagen-like protein, has shown to be specific for B. Anthracis spores.  Information on B. Anthracis can be obtained from the US Centers for Disease Control (CDC) CDC - Anthrax and the World Health Organization (WHO) WHO - Anthrax.

Research indicates a number of applications where VLR's can recognize certain immumogens  An immunogen is any antigen that is capable of inducing humoral and/or cell-mediated immune response rather than immunological tolerance.  These applications include diagnosis, research and bioterrorism investigations.