Biology of Aging

Senescence is a fancy word for old age, used in scientific papers. There is no consensus definition of the hallmarks of senescence, even among gerontologists. Chronological age is probably the most common metric and some academic studies define elderly as those past a certain age. That age differs depending on the field (sociology, labor, etc.) and what the investigators are looking into (e.g. muscle weakness, strokes in those past 80 years, etc.)

Senescent as an adjective does not refer to an old person. It means an aging person. In microbiology senescent refers to a cell that has stopped dividing.

Mikhail V. Blagosklonny of Roswell Park Cancer Institute wrote "Aging is the sum of pre-diseases and diseases." Another definition is: Aging as a progressive increase in death rate.

Is old age a disease?
Traditional answer: no
Some people in the biotech industry are approaching aging as a disease. They think they can make us live longer by boosting the immune system. Other approaches include curing or stalling the progression of fatal diseases.

Difference between disease and illness.

Modes of Health

  • cognitive
  • emotional
  • physical

Theories of Aging

The aging process is highly individualized and in any one person affects many physiological systems. There is no accepted theory of aging that fits all observations and that experts agree upon. One way to categorize the theories is into two types: (1)programmed theories and (2) damage theories.

Programmed Aging

Endocrine Theory

When the hormone system breaks down, the body ages.

Telomerase Theory of Aging

Hayflick limit theory of aging - cells can divide a maximum of 50 times.

Immune System Theory

The immune system is complex and not well understood. However, it is known that the effectiveness declines over time. As it declines, the body is subject to more diseases. Another malfunction can make the immune system turn on the body, leading to autoimmune diseases.

Damage or Error Theories

Molecular damage theory of aging

This is how many people with some understanding of biology or physiology imagine the body ages, but closer examination shows it’s not so clear. The body’s cells turn over so by the time you are 70s few of your cells remain from when you were 20. Damage occurs to biomolecules - cell membranes, DNA, etc, but the body has processes to repair damage. If there were no repair, we would die pretty quickly. And it is not clear that the characteristics of old age are due primarily to molecular damage. Heavy molecular damage can be fatal - that’s what happens when people die from poisoning or injury.

The Oxidation (or Free Radical) Theory of Aging

This theory gained purchase because it’s easy to understand if you know a little chemistry. Oxidation is sometimes the way food spoils. Food preservatives are anti-oxidants.

The idea is that superoxide and other free radicals cause damage to nucleic acids, lipids, sugars, and proteins. Free radicals form in the normal course of living, and the body has natural antioxidants to keep them from doing too much damage.

Some foods we eat contain chemicals that can be classified as antioxidants. In laboratory glassware - in vitro they call it - these chemicals stop or slow oxidation reactions. People got the idea that if you swallow antioxidants - either in food or dietary supplements - you reduce oxidation inside the body and hence illness, disease, or aging.

While it has never been resolved whether antioxidants reduce your change of short-term illness, their effects on long-term aging are even more unclear.

Wear and Tear Theory

This is an old idea - first articulated in the Nineteenth Century - and it appeals to us because it seems logical. Machines wear out so people think human bodies will, too. But no one who understands biology and physiology accepts this theory any more.

DNA Damage Theory

DNA is the molecule that carries genetic information and cell division (reproduction) relies on duplication of DNA. There are errors during the duplication, and sometimes there make the cell cancerous.

Chronic Inflammation Theory of Aging

Inflamm-aging or Inflammaging

One old theory - no longer widely believed - was that chronic inflammation caused the worst physical maladies as we age. Elderly people must therefore be plagued by low-grade, chronic, systemic inflammation in this view, even though empirical data shows that not to be the case. It is true that inflammation is generally a negative thing. It is often painful and inflammation is a symptom and sign of another disease. Even if the underlying cause cannot be identified, inflammation is considered to have negative effects. Inflammation of the cardiovascular system can increase the chance of heart disease. Anti-inflammatory drugs such as aspirin exist and some plants are thought to have beneficial life-extending effects because of this.

The network theory of aging posits that aging is indirectly controlled by the network of cellular and molecular defense mechanisms.

The remodeling theory, which was put forward to explain immunosenescence, is the gradually adaptive net result of the process of the body fighting malignant damage and is a dynamic process of optimization of the trade-off in immunity.

Evaluating Effective Age

Doctors often look at gait speed to predict how well a person is doing. Generally speaking, the slower a person walks, the greater the risk for disease and death. Measuring gait speed is an element of a geriatric assessment. People with slow gait speeds have smaller brains and perform worse on cognitive tests than fast walkers.

Walking speed even is a useful insight into middle-aged people. Researchers found that people with a slow walk had progressively aged more rapidly up to age 45 than faster walkers had. They concluded gait speed in middle age indicated a propensity to lifelong brain health.

mTOR Inhibitors

Biochemists have elucidated a nutrient response pathway that is mechanistic target of rapamycin (mTOR). Experiments in animals have shown that when certain chemicals (drugs) are inserted that inhibit this pathway, the animals live longer and experience fewer signs of old age. These results have incited interest in developing mTOR inhibitors for use in extends lifespan in model organisms and confers protection against a growing list of age-related pathologies. mTOR inhibitors have been approved by the FDA for cancer treatment. There are none approved for general aging.

Rapamycin, Everolimus, and Temsirolimus are approved for medical use in some form. Rapamycin (also known as Sirolimus) is used to facilitate organ transplants. mTOR as Regulator of Lifespan, Aging, and Cellular Senescence: A Mini-Review

Nature magazine had an interesting article about calorie restiction diets and Rapamycin as a way to fight aging.

Geriatric Syndromes