Article Type : Short commentary
Authors : Bando H
Keywords : Anti-aging medicine; Oxidation; Reactive oxygen species (ROS); Advanced glycation end product (AGE); Low carbohydrate diet (LCD)
Anti-aging
medicine has been important with adequate lifestyle and prevention of diabetes
and cardiovascular diseases. Some hypotheses of aging process have been
accepted as three axes in the following: i) oxidation: reactive oxygen species
(ROS) are molecules capable of independent existence, including oxygen free
radicals, ii) intestinal flora: healthy microbiota bring benefit for immunity,
cancer, sarcopenia, inflammation, cardiovascular and oxidative stress, iii)
glycation: advanced glycation end product (AGE) may be important causes for
aging process. AGE lead to metabolic abnormalities, then low carbohydrate diet
(LCD) would be beneficial. This article will be hopefully a reference for
future research development.
Recently, the crucial problems concerning
COVID-19 has been continued across the world. Usual daily life related to
anti-aging medicine seems to be considered [1]. Among them, anti-aging measures
have been important especially for prevention of diabetes and cardiovascular
diseases [2]. In the progressively aging population, the ultimate goal would be
conducting primary and secondly prevention of diseases and reducing
socioeconomic impact of age-related impairments. It is necessary to raise some
adequate markers which can identify the person with possibly risky situation of
vascular damage [3]. In this article, some meaningful information would be
described concerning anti-aging medicine, factors of biological aging,
cardiovascular influence and adequate diet with carbohydrate
For long years, there have been some well-known
questions about anti-aging medicine. Why do people get old? Can we get any
drugs with dramatic effects on aging? Is there an immortal medicine? There are
no apparent ideal answers to these. As a reference, meaningful comment was
present from a prominent physician, Sir William Osler (1849-1919) [4]. He left
the phrase that “A man is as old as his arteries”. The human body is finite,
and all organs are declined with age. For its fundamental phenomenon, blood
vessels may become older as arteriosclerosis associated with age, and some risk
factors may accelerate aging process of blood vessels. Traditionally, some
hypotheses for aging process have been accepted. They are three axes, which are
oxidation, intestinal flora, and glycation. These outlines and some topics were
described in the following.
Humans always produce and consume energy by using
oxygen. Among them, some of them may become "superoxide" which is
difficult to prevent [5]. Human cells obtain several useful systems which can
remove harmful superoxide. However, if superoxide may be present beyond the
capacity, the cell will be influenced to dysfunction or cell death. An
oxidative theory means that this accumulation would be the basic mechanism for
aging process. For adequate measures, to take certain particular molecule is
possible that can clear superoxide. Reactive oxygen species (ROS) are molecules
capable of independent existence, including oxygen free radicals [6].
Production of free radicals is increased by long-term stress conditions,
improper diet, intense physical exercise, use of stimulants and excessive
exposure to ultra-violet radiation. ROS may bring chemical modifications and
also damages to carbohydrates, proteins, lipids and nucleotides. Thus,
oxidative stress causes a special adverse effect on cardiovascular, respiratory
and nervous systems [7].
Intestinal bacterial flora has been recently
investigated and reported for anti-aging region [8,9]. Generally, they are
roughly divided into beneficial and non-beneficial bacteria. Aging seems to be
related with the accumulation of several toxins from intestinal bacteria. Human
healthy aging can be obtained by reducing the risk factors which may cause
various damage and pathologies with aging. These factors can been modified
through adequate nutrition and intestinal microbiota [10]. Healthy microbiota
will bring benefit for immunity, cancer, sarcopenia, inflammation,
cardiovascular, oxidative stress, neurodegenerative diseases. They include
fibers, fats and polyphenols, such as Mediterranean diet and oriental diet
[11]. Regarding the therapeutic method, intake of some probiotics such as
yogurt for increasing beneficial bacteria and reducing non-beneficial bacteria
and others [12].
It means a phenomenon that human cells have various
damage and deterioration due to the influences of excess carbohydrates taken by
meals [13]. Glycation is the biochemical condition that advanced glycation end
product (AGE) produced by the combination of protein and carbohydrate would act
on tissues and/or cells in the body, and that this may be one of the important
causes for aging process [14].
AGEs have been in focus for impaired function of
metabolism. AGEs are heterogeneous group of molecules from the interaction of
reducing sugars and amino acids, proteins, nucleic acids and lipids [15]. They
are made from normal metabolic consequences and are also absorbed from the
meal. Elevated AGE values may influence metabolic health and bring to metabolic
abnormalities such as diabetes. Due to hyperglycaemia, AGE levels are
increased, and AGEs will stimulate signalling pathways with compromising
pancreatic beta-cell function. Furthermore, AGEs may exacerbate the obesogenic
influence from Westernized meal by increasing hypothalamic inflammation and
disrupting the control of energy balance [15].
AGEs are organic molecules which are formed in all
living organisms associated with various structural and functional properties.
As they show a variety of heterogeneity, no specific examination for the
operational detecting measurements [16]. However, there have been several
trials for AGE present in biological samples using serological,
chromatographic, spectroscopic and colorimetric methods. For the therapy and
protection of glycation, it would be beneficial to make limitation of in taking
carbohydrates in the daily life [17]. As to nutritional therapy for
carbohydrate amount, lots of discussions were found concerning calorie
restriction (CR) and low carbohydrate diet (LCD). LCD was begun in Europe and
North American by Atkins et al. [18]. After that, various controversies were
continued [19], and Bernstein and et al. have summarized the standard concept
and treatment for LCD [20].
Authors and collaborators have continued clinical
practice and research concerning LCD for long. We investigated glucose
variability in patients with type 2 diabetes mellitus (T2DM) and research on
ketone bodies (KB), M value and continuous glucose monitoring (CGM) and others
[21]. We also reported the clinical significance of elevated KB for
mother-new-born-placenta-fetus axis [22]. Further, practical LCD methods were
proposed for medical and health care region. They are petite-LCD, standard-LCD
and super-LCD, which contains carbohydrate ratio as 40%, 26%, and 12%,
respectively [23]. The ketogenic diet from LCD has been effective for various
patients with T2DM, obese and sarcopenia [24].
In summary, some topics concerning anti-aging,
oxidation, intestinal flora, glycation, LCD and cardiovascular diseases were
introduced [2]. The important points include that i) cardiovascular aging and
longevity may have common pathophysiological characteristics, ii) delaying
cardiovascular aging may improve longevity and iii) recommended regimen include
LCD, Mediterranean diet, CR, physical activity, associated with favourable
genetic and environmental background. This article will become hopefully a
reference for future development of anti-aging medicine.