Harvard Medical School – A 13-year international study in mice demonstrates that loss of epigenetic information, which influences how DNA is organized and regulated, can drive aging independently of changes to the genetic code itself.
It also shows that restoring the integrity of the epigenome reverses age-related symptoms.
Mutation is engrained in the very nature of life. Even if there were no X-rays, free radicals or toxic chemicals, mutation still would take place because of errors in the replication of DNA that occasionally escapes the proofreading mechanisms of meiosis and mitosis.
The majority of germline mutations produce LOSS OF FUNCTION, and are weeded out by evolution. In vertebrates, mutation is vital in producing the random changes in the DNA of germ cells of the ovaries and testes. If the mutation is beneficial, involving a GAIN OF FUNCTION, environmental selection acts to preserve the change, producing the diversity of organisms in the world, each exploiting a different environmental niche.
It is the rare species so versatile, like the shark, that can remain almost the same over eons without dying out. In the teeming unicellular world, mutation in the genome is similarly useful in allowing for variations which often prove useful for survival. The mutations thrive if the proper environment presents itself. For instance, antibiotic resistance may be encoded in a few members of a bacterial species, which become the dominant members in an infected patient on antibiotic treatment, and crowd out family members without the mutation.
In Viruses, RNA is often the Memory nucleotide. RNA is less stable than DNA. The resulting instability allows more mutations, and sometimes greater success. An example is the English Covid variant in the spike protein which leads to greater contagion. Hopefully, the spike protein change will not be so successful as to interfere with the effectiveness of vaccine-produced protective antibodies.
The Mutations we have been discussing refer to GERMLINE mutations, which occur in the gonads. In higher animals, germline mutations affect the offspring, which then carry the mutation. A GAIN OF FUNCTION mutation may confer greater adaptability and survivability, and perhaps may lead even to a different species, if the troop number is small and the environment demanding. Non-germ SOMATIC cell mutation may lead to undesirable effects like cancer, which is another discussion.
The RNA molecule is central to life. It is the information molecule of the Pandemic SARS CoV 2 virus, whose Messenger RNA specifying Spike proteins is the basis of 2 recently-released vaccines.
“RNA Life” is the leading theory for the Origin of Life itself, more than 3 Billion years ago. DNA evolved as the blueprint information molecule in cellular life, but the ubiquitous RNA may well have become the first viruses.
The stage was set for the ongoing battle of life: Parasite vs. Host, Pathogen vs. Target, but recent research reveals a much more nuanced picture. Viruses and bacteria can be BENEFICIAL as well as deleterious. We now speak of the MICROBIOME, usually referring to our host of resident BACTERIA, and the VIROME referring to all of our indwelling VIRUSES.
INFECTION is how we experience our interaction with microorganisms, their benefits unseen. Bacteria, viruses and parasites have always been with us, increasing in impact as Paleolithic man crowded into agricultural settlements.
Enlarging cities became more dense, favoring spread of infection and PLAGUES. The Bacterium, Yersinia Pestis,emerged in Roman times, causing the Justinian plague, and resurfaced in the 14th C. as the Black Death. Viral Plagues, including Smallpox, were devastating during European adventures into the New World.
Malaria, a one-cell Eukaryotic Parasite, may be the greatest killer of all time. Modern Sanitation and improving medication have lately pushed bacterial infections into the background.
Viral infections such as Influenza and most recently Covid have become the Modern face of infection. Many Viruses reduce Immunity, however, paving the way for bacteria to invade: Haemophilus influenzae, a bacterium, may have caused much of the mortality of the 1817-1918 Flu epidemic.
IV drug usage has facilitated the spreading of the viruses causing Hepatitis and AIDS. The immune-compromising nature of the latter has reinvigorated TB and Syphilis, both bacterial infections. Only a few years ago, bacterial infection was thought to be conquered by antibiotics, and viral infection contained by Vaccines.
Microorganisms are constantly evolving, however, and often share their resistance factors. Infection is no more a thing of the past than War. The Battle continues.
Old age is an inevitable condition if you are lucky enough to live a long life. Middle aged people say it begins at 70 years of age. According to an Elysium survey of people 40 and older, the average American FEELS old for the first time at age 47 years.
In the distant past, 50 was CONSIDERED to be old. The generally better conditions and Medicine of modern times keeps extending LIFESPAN, if not always HEALTHSPAN. Old age is certainly a Condition, and it is for sure Chronic, thereby qualifying for inclusion, but is it a Disease?
It is not considered a disease by the authorities, and so it doesn’t gather research funds like it should. What exactly IS old age? Being 88 Years old, and a physician, I feel qualified to comment. Old age is a collection of past accidents and sports injuries plus complications of past illnesses engrafted on a gradually deteriorating body.
Where does Obesity and Metabolic syndrome fit in this rubric? The Plague of our time fits in the disease category. It is definitely preventable, although with difficulty. Please search past postings for more information on this topic.
In what way does the body gradually deteriorate? Any organized, non-random high information structure gradually becomes more disordered, and “worn away” with the passage of TIME, the destroyer. Entropy (disorder) gradually increases, in the absence of corrective energy input.
Even rocks and mountains eventually erode, given enough time. One of the most interesting characteristics of life is that it maintains its integrity for an inordinate amount of time, given its complexity and furious dynamism.
Every day our DNA sustains thousands of molecular ruptures from high energy radiation and other stressors. Proofreading and repair mechanisms are employed, at high energy cost, to repair these breaks. This corrective is especially efficient when we are young and vigorous; In our youth, our reproductive years, growth and repair predominate. Gradually, growth ceases, repair mechanisms age, and we become old.
Our Darwinian “warranty” expires. We are left with an aging body, unimportant to evolution. We are long on experience and short on future. But we still have a marvelous metabolism at our disposal, depending on our lifestyle. There are a number of metabolic pathways which affect aging, 2 of which have been more studied.
The mTOR pathway is most attuned to youth, senses nutrients and gears up for ANABOLISM, or growth. If you have not been careful to tailor your food intake to suit your decreasing requirements, your efficient metabolism stores it away for a rainy day, around your belly and in your arteries, a bad effect from an essential mechanism. Antagonistic Pleiotropy is the name for a body mechanism that can be good for one function (or age) and bad for another.
The Sirtuin system is also important in aging, and has a variety of housekeeping functions, including mitochondrial maintenance. It is activated by exercise. The cells of our bodies change with aging. In old tissues, there are less stem cells and other young, functional units. There are more damaged, dysfunctional “zombie” cells that don’t do much but promote inflammation, and hence more inflammatory cells accumulate.
Controlling the mTOR System and promoting the sirtuins help increase apoptosis and get rid of dysfunctional cells, including cancer. DOCTORS SHOULD PRESCRIBE EXERCISE, as well as SLEEP AND DIET, like they do medicine, and maybe we wouldn’t need so many pills. We might also feel better into old age.
Several ideas apply to ALL MEDICINES. Terminology should be clarified. Medicine, Pharmaceutical, and Drug, in my mind are equivalent.
The term “drug” is pejorative, and I try to use it so. The term “Pharmaceutical” is too long, leaving me with “medication”.
There are some Practical points. You should look at your prescription when you first get it, to make sure it is the right one. Yes, pharmacists rarely make some mistakes. They are human.
You should ask the Pharmacist if she knows WHERE the drug was manufactured. Foreign countries, especially China and India, are less reliable, and the USA is safer. The original Brand Name drugs are more often domestically produced, but even these are being “offshored”.
Next, check the prescription date and expiration date.You should get a ” SHELF LIFE” (the difference between the two) of about 2 years, otherwise, you might ask the pharmacist the next time to give you the “best dating” in his stock.
Store your medications in a cool, dark, dry place in order to prolong their life. Light, heat and moisture degrade most compounds. Remember the O.J. Simpson case? Part of the reason he was acquitted is that a critical DNA sample was stored in a plastic bag, which retained moisture, rather than a paper bag, which is recommended because paper is porous, and allows moisture to escape.
You should follow the suggested TIME to take the medication, because there is almost always an optimal time to take a given medication.
CHRONOPHARMACOLOGY is an emerging field, which is finding that more than 50% of medications are TIME SENSITIVE in their effect in the body. This is an unimportant, academic consideration for most Patients, given the high THERAPEUTIC WINDOW (dosage latitude) of most medications, the mild illness of most patients, and the disinclination of most Doctors to add one more detail onto their already heavy load.
In discussing the medicines in my cabinet and a few other important ones, I will be addressing TIMING.
What about OUTDATED MEDICATIONS? As discussed by the following article from Harvard, the dating is not critical except for liquids, and a few others, like Tetracycline.
This is fortunate, given the expense of medications today. What if I drop a pill on the floor, at home. I usually pick it up and take it. if i just dropped it, unless it is very inexpensive.
What if a pill sticks in your throat, like happens to me a lot? I drink water first, to moisten my throat to make it slipperier.
Next, I take a good sip of water, try to swish it back and go back with my head to accelerate the pill backward, and think confidence. Certain sizes of pills are my nemesis and i have to break them in two.
Please follow Dr. Cs Medicine Cabinet in future postings of DWWR.