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Understanding the Mechanism of Aging—Aiming to Realize Healthy Longevity

Takuya Chiba
Professor, Faculty of Human Sciences, Waseda University

Why does aging occur?

Aging irreversibly decreases the body’s functions and its ability to resist external factors, ultimately resulting in death. In the stages of evolution, why have aging and limited lifespans, which are disadvantageous for species conservation, not been eliminated? It wouldn’t have been surprising if human evolution had resulted in an extreme organism that lived eternally without aging.

Over the long process of biological evolution, various changes have occurred in our environment, and gene sequences were altered to adapt to these environmental changes. Because species composed of individuals with exactly the same genes are thought to have the same characteristics, if one of those individuals cannot survive in an environment, none of the same species will survive. For instance, there is a risk that organisms that are strong against heat but vulnerable to the cold could become extinct if an ice age were to occur. Therefore, organisms that reproduce through male and female mating came into existence. Different genes mixed and were gradually passed down from parents to their children. Such reproduction increased the number of offspring with diverse genes, resulting in the survival of well-adapted individuals over what is known as the process of evolution. Meanwhile, organisms that engage in sexual reproduction cannot change decreased physical functionality once reproduction takes place, meaning, it cannot influence selection related to aging.

There is also another possible reason related to sexual reproduction for why aging and limited lifespans remain. Genes that play an important role for increasing the survival rate while the organism is young could actually have an adverse effect after sexual reproduction. This is called the antagonistic pleiotropy hypothesis of aging. Let us take growth hormone genes as an example. Growth hormones are essential for human development. However, once growth and reproduction end, they may encourage the proliferation of cancer cells. Reproduction is crucial for survival of the species. Yet, as organisms usually engage in reproduction well before their expected lifespan, individuals may actually have genes that are detrimental to its life at the time of completing reproduction.

Experiments have shown that the earlier the reproduction period, the shorter the offspring’s lifespan becomes. Conversely, the offspring’s lifespan becomes longer if the reproduction period is later. Moreover, the records of women of the English aristocracy have shown that women who lived longer had their first child later in life and had fewer children. Thus, there appears to be a tradeoff relationship between sexual reproduction and aging, affecting lifespan.

How does aging occur?

The causes of aging are currently believed to be “rusting” and “browning” in the body. Rusting is scientifically referred to as oxidation. It is related to the weakening actions of mitochondria, which are organelles found within cells. Many organisms inhale oxygen and exhale carbon dioxide, and sometimes, oxygen is converted into toxic molecules called reactive oxygen species (ROS) inside the cell. Also produced when water reacts with ultraviolet rays or ionizing radiation, ROS react with and change the characteristics of surrounding protein, fat and DNA because of its extreme instability. This is how oxidation causes damage to the body.

As observed in cooking, browning is caused by Maillard reaction, which occurs when dextrose (glucose) reacts with protein. Dextrose exists as blood glucose, and there is a large amount of protein in the human body. Thus, the Maillard reaction occurs at normal body temperature. Diabetes patients in particular, who have high blood glucose levels, are more prone to this reaction than healthy individuals. This rusting and browning are thought to be factors that speed up the aging process.

Can aging be prevented?

The aging phenomenon is thought to be progressive and irreversible. However, recent research using animal experiments is gradually making it possible to delay aging and enable rejuvenation. Eating in moderation is often said to lead to a long life. In an animal experiment, aging was delayed and lifespans were prolonged in animals only fed until they were 70% full compared to animals that were allowed to eat as much as they liked. While its reasons remain unknown, it is possible that aging could be slowed down by avoiding rusting and browning. In fact, it is becoming known that appetite-regulating factors may play important roles in preventing such rusting and browning.

Since it is difficult for humans to continue restricting their diet long-term, research groups are investigating drugs that can produce the same anti-aging effects without actually reducing food intake. While this may seem unreal, clinical trials using different drugs on humans were initiated in the U.S. and Japan in 2016. My team is also engaging in original research on such substances.

How to prolong healthy longevity

While there is no need to implement excessive food restrictions, you must be careful of what and how much you eat. For example, there is scientific evidence which indicates that the following may prevent aging: (1) eating only when you are hungry, (2) eating dietary fiber first, then proteins, with sugars ingested last, (3) limiting the intake of carbohydrates such as rice and bread, (4) eating slowly and gradually as it takes time for the satiety center to be stimulated, and (5) eating a different kinds of foods and seasonal ingredients.

Much of the active components of foods for specified health uses (FOSHU) and functional foods displays are known be antioxidants, which prevents rusting in the body. While it is best to consume such components through fruits and vegetables, ingesting them efficiently, from products recognized as having health-promoting effects and supplements, is important in some cases.

Is everything about aging bad?

Fluid intelligence, which includes the ability to solve new problems, starts to decrease from a relatively younger age. Meanwhile, it has been reported that the ability to use learned knowledge and experience, which is called crystallized intelligence, is maintained until around the age of 60, after which it gradually declines. In light of this, it appears that the operation of various organizations requires a balanced age composition. Moreover, once individuals reach their 80s, in spite of their decreasing physical function, they display more positive emotions of accepting their current lifestyle and increased satisfaction regarding the life that they have lived. It is said that many individuals who are over 100 years old tend to feel happy with everything in their lives (euphoria).

In order to be physically and mentally healthy as well as happy when you’re older, lifestyle habits need to be reviewed. With elderly individuals contributing to local communities and societies, I believe that achieving healthy longevity is a major step in overcoming the problems associated with our nation’s declining birthrate.

Takuya Chiba
Professor, Faculty of Human Sciences, Waseda University

Takuya Chiba was born in Mie Prefecture in 1971. In 2001, he completed the doctoral course at the Graduate School of Medicine and Faculty of Medicine, Kyoto University and received a PhD in medicine. He also became an assistant professor at the School of Medicine, Nagasaki University in 2001. In 2009, he became an associate professor of the School of Medicine, Nagasaki University. In 2014, he became a professor at the Faculty of Human Sciences, Waseda University.

Professor Chiba specializes in the molecular biology of aging, experimental pathology and molecular nutritional chemistry. His major publications include First Steps for the Basic Life Science in Human Sciences: Gerontology and Pathology (Corona Publishing, 2016), Food and longevity genes, Bioactive Food as Dietary Interventions for the Aging Population (Elsevier, 2013) (co-authored).

Takuya Chiba research laboratory