What is aging?(1/2)

In today's world, where the number of people requiring care and dementia patients is increasing as society ages, the topic of recent discussion is ``Can aging be treated?''“tomorrow is mine”This is likely to be of interest to middle-aged and elderly citizens. Are you seeing more related articles in general magazines and on the Internet? . A book written by an aging researcher claiming that aging can be cured becomes a bestseller.、In recent internet news, a lecture at an international academic conference on the theme of rejuvenation was flooded with audience members, causing a commotion that resulted in the police being called out. It is reported that.

In the B.C. era, when natural science was not an independent discipline, the Roman philosopher Cicero said, ``When an old man dies, it is like a burnt-out fire extinguishing itself without any effort,'' and he believed that aging was not a disease. Metchnikov, who can be said to be the father of modern gerontology (known for claiming that aging can be cured with yogurt)

thought of aging as a disease. I want to cure aging.

My desire is to find a medicine for eternal youth and longevity.49It has continued uninterrupted since the time of Emperor Qin Shihuang, who is said to have died at the age of 50.

To claim that aging is a disease means to believe that it is treatable. In this paper, we consider the possibility of aging treatment based on scientific findings from recent aging research.

What is aging? Definition of aging

When considering the possibility of aging treatments in light of modern scientific knowledge, the discussion will not be coherent unless it is clear how aging is defined. Here, aging is considered to be a phenomenon that occurs in common among animals with generally similar systems. Non-human model animals are used in aging research, which have various limitations. These include unicellular eukaryotes (budding yeast, Paramecium, etc.), normal diploid cell division and aging in vitro (human skin cells, vascular endothelial cells, etc.), and multicellular animals such as mice, fish, fruit flies, and nematodes.

However, aging in model animals often differs in substance even if they appear similar, and even experts sometimes deliberately do not differentiate between the two in their discussions, so caution is needed when interpreting research results.

University of London zoologist who gave a famous lecture on the fundamentals of aging more than half a century agoPeter MedawarAbout aging, ``Iageing The word is used when simply referring to aging. When referring to the decline in physical vitality associated with aging,senescence"I use the word "®. Aging is simply a physical quantity that refers to the passage of time, including inanimate objects, and aging refers to changes in biomass, such as a decline in biological functions.

In Japanese, for example, the word anti-aging medicine is used without distinguishing between the two, even when the term anti-aging medicine is considered more appropriate.”. In this paper, we will use Medawa's concept of aging as a principle. senescenceused in the sense of

In this usage, aging can be defined as ``the progressive decline in biological functions that causes an age-related decline in survival after reproductive age.'' Survival rate is expressed with the population in mind, but the decline in biological functions is an individual problem, and it occurs in all individuals (individuals) as they age, although the rate may vary.

In gerontology, the expressions physiological aging and pathological aging are sometimes used, but the boundaries between the two are often unclear. Pathological aging can be said to be a precursor state or a transitional process that can lead to geriatric diseases.

For example, recently there has been a lot of talk aboutMCI （mild cognitiveimpairment ）can be said to be a precursor to the disease known as dementia (pathological aging).

Aging changes in human biological functions

Age-related changes in human biological functions are25～35It declines almost continuously throughout one's life from around age.

Since there is no change in the tendency for functional decline to occur almost continuously with age, this pattern of change can be considered to be generally applicable.

Curing aging means slowing down the decline or reversing the changes.

The longest lifespan is the survival curve of a model animal whose lifespan is significantly different from that of humans.1,000Humans (tens of trillions of cells) and C. elegans (approximately 10 trillion cells) are more than twice as different1,000), the curves almost overlap, and the aging rate of change in various biological functions often differs by approximately this percentage (for example, humans and mice/rats have approximately the same rate of change).30twice as different). Commonalities can also be seen in age-related changes in individual functions. These facts suggest that aging in humans and aging in animal models may occur through a common mechanism.

However, the mechanisms of aging changes may or may not be common between animal species or tissues within the same species. The former is caused by oxidative damage, protein abnormalities, etc.Public mechanismSaid. The latter is caused by, for example, immune abnormalities and endocrine insufficiency.PrivatemechanismIt is called. This paper mainly focuses on mechanisms that are considered to be universal.

Aging mechanism theory

In discussing whether aging can be cured,300Among the aging mechanism theories (aging theories) that are said to exceed the above, we will select and discuss the main ones.

1.cell nucleusDNATheory that the cause is due to injury (mutation accumulation theory/genome destabilization theory)

This theory was based on research on nuclear fission and fusion, and was based on the idea that radiation exposure shortens the lifespan of experimental animals, and that natural radiation such as cosmic rays damages genes, which is the cause of aging.”. Early research showed that mutations in dividing cells, the main target of radiation, can cause cells to become cancerous, resulting in shortened animal lifespans, but research was temporarily stalled because no link was found to a decline in general biological function. However, with the development of genetic engineering technology, the frequency of genetic mutations in slowly dividing cells or non-dividing cells (cells that have completed division) has been investigated and research continues.

As a result, tissue consisting mainly of non-dividing cells, such as cranial nerves and cardiac muscle, in model animals.DNAMutation frequency increases with age (e.g. in humans)70.80equivalent to age30It became clear that even when the mice were 3 months old, they were not high enough to explain the decline in function. Although this theory has some support in recent years, it is unlikely to be the main aging mechanism because the frequency of changes is much lower than the rate of functional decline.

2.Theory that the cause is oxidative stress (free radical theory/oxidative stress theory)

A theory that aging is caused by radicals, chemical substances that are not familiar to the general public, that cause damage to various biomolecules. Initially, oxygen-derived radicals were mainly considered, but non-radical oxygen-derived highly reactive substances (ROS： reactive oxygen speciesIt has become clear that oxidative stress (e.g., hydrogen peroxide) can also cause injury, and this is now often referred to as the oxidative stress theory. This theory was not given much attention until the discovery of an enzyme that scavenges superoxide (the first radical produced from oxygen) in living organisms.

reference). However, since then, a huge amount of research has been carried out, and it has been discovered thatROSare cell membrane lipids andDNA・It has been revealed that it causes various damages to biopolymers such as proteins.

Therefore,ROSBased on the idea that the progression of aging can be suppressed by eliminating radicals, radical scavengers, antioxidant supplements, and antioxidant enzymes (ROSerase

Numerous studies have been conducted on the effects of introducing surplus genes (enzymes). However, no conclusive evidence has been obtained to support this theory.

ROSIt is known for its diverse roles, including the role of a signal transduction factor that regulates gene expression, and reports that at low levels it exerts anti-aging effects through hormesis (a harmful effect at high doses, but a beneficial effect at low doses, such as by inducing and synthesizing antioxidant enzymes and activating defense mechanisms). Based on these effects, it should be considered that attempts to control aging by suppressing oxidative damage by ingesting powerful antioxidants are fraught with problems.

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