Journal of Gerontology & Geriatric Medicine Category: Medical Type: Review Article
Psychosomatic Health and Serum BDNF, Brain-Derived Neurotrophic Factor, in Elderly People
- Mitsugu Hachisu1*, Masahiro Hashizume2, Mari Kogo1, Kazushige Ihara3
- 1 Department Of Pharmaceutical Therapeutics, Division Of Clinical Pharmacy, Pharmacy School, Showa University, Tokyo, Japan
- 2 Department Of Psychosomatic Medicine, School Of Medicine, Toho University, Tokyo, Japan
- 3 Department Of Social Medicine, Hirosaki University School Of Medicine, Hirosaki, Japan
*Corresponding Author:Mitsugu Hachisu
Department Of Pharmaceutical Therapeutics, Division Of Clinical Pharmacy, Pharmacy School, Showa University, Tokyo, Japan
Received Date: Apr 24, 2019 Accepted Date: May 08, 2019 Published Date: May 15, 2019
Developed countries including Japan are higher senior citizen’s country and the population of elderly people of over 65 years old occupied almost close to 1/3 of the whole population in the country. To prolong the healthy life expectancy which elderly people can make a life vigorously by themselves without caregiver’s help is important for the individual’s happiness and reduction of social security costs. We have reported that individuals having thick quadriceps muscle and/or higher BMI show higher serum BDNF levels in a paper of “Relationships between brain-derived neurotrophic factor concentration and parameters for health scores in community-dwelling older adults”. Geriatr Gerontol Int 2017 BDNF has properties to enhance neurogenesis and inhibition of neuronal apoptosis in the brain and reported lower serum levels in the Alzheimer’s disease and depression. Therefore, to keep higher serum BDNF values protects from Alzheimer’s disease and the depression etc. We have reviewed and discussed how can aged people to keep higher serum BDNF levels doing exercise, consuming a nutrient meal and supplements with the evidence.
Population of elderly people of 65-years and over in Japan is figure of 34,590, 000 at September 2016, and stand up to 27.3% of Japanese total population (Just for reference, 75-years and over is 13.3%.), top class aging country among the developed countries . The work force of 65-years and over is 20.1% in total worker in Japan and this rate is top in the world, then it is 17.7% in USA >12.5% in Canada. The average life expectancy of Japanese at 2015 is 86.6 (87.14 in 2016) years old and 80.21 (80.98 in 2016) years old in women and men, respectively. The healthy life expectancy which means a span with health and independently making a life without caregiver’s help is 74.21 years old and 71.19 years old in women and men at 2015, respectively. The difference between the average life expectancy and the healthy life expectancy is 12.4 and 9.02 years in women and men, respectively . To expand the healthy life expectancy and to shorten the period receiving caregiver’s help links to one’s happiness and reduce a cost of social security. To expand of health life expectancy may be kept with a good lifestyle including healthy meal, exercise and positive thinking with reducing stress. In case of meal, vegetables with much of vitamins and high dietary fiber, and meat and fish with high protein content should take much and carbohydrate and fat intake should lessen. Taking foods with much anti-oxidative activity is necessary activating longevity-related genes. Moreover, exercise is important to produce neurotrophic factors and development of skeletal muscles, cardiovascular and respiratory systems as well as energy consume and fat metabolizing. For the vivid daily living, a parson had better to make a life with positive thinking and reduced stress. We would like a review concerning to healthy life of elderly people based on our paper of “relationships between serum BDNF values and various health parameters” .
BIOLOGY AND THE ROLE OF BDNF
Neurotrophins having activities to promote neuro-survival, maintenance and to protect apoptosis of neurons etc., and is produced by neurons. Among the neurotrophins, BDNF is present most abundantly and various regions in the brain . BDNF has various activities, i.e. neurogenesis, neuro-survival, growth of axons and dendrite and synaptogenesis. BDNF is processed from precursor-BDNF (pro-BDNF) synthesized by activation of CREB through various neurotransmitter signals . The BDNF is processed from pro-BDNF intracellularly and extracellularly [6,7]. The pro-BDNF has opposing action of BDNF i.e., induce neuronal apoptosis  and hippocampal long-term depression . The BDNF paths through blood brain barrier from both sides [9,10]. It is known that the serum BDNF contents are low at depressed patients and Alzheimer’s disease when compared with healthy people and are restored by the medication [11-13]. The BDNF contents elevated in the brain of rats housed in enriched environment which provide tunnels, platforms, balls, ladders and toys, and housing with several rats for social stimulation . The gender difference of serum BDNF levels is controversial. Komulainen et al., reported  higher serum BDNF level in women among 57-79 year-old elderly people, while Murawska-Cialowicz et al.,  that is higher in men at 20-30 young adults. We observed no difference between the sex i.e., 9.52±4.38 ng/ml (n=304) in male and 9.33±3.80 ng/ml (n=501) in female, respectively . BDNF is considered to be expressed in the central nervous system at initial period of discovery, while it is also found the expression in the muscle, especially in satellite cells . Expression of BDNF is enhanced by the exercise and excreted to extracellularly. Especially, satellite cells located around the skeletal muscle express BDNF and regenerate skeletal muscle by differentiating the satellite cells itself . Moreover, BDNF enhance glucose uptake into skeletal muscles and contributes energy metabolism . Therefore, BDNF takes a role to promote mental health and physical health through central nervous systems and peripheral muscles activity, respectively.
BDNF level is usually measured By Enzyme-Linked Immunesorbent Assay (ELISA) kit and the BDNF antibody is cross-reactive with pro-BDNF . So, the most reports measured BDNF levels possibly express the levels of both BDNF and pro-BDNF. Conversely, pro-BDNF ELISA kit does not cross reacts with BDNF .
Exercise and BDNF
We have mentioned that measured BDNF with BDNF-ELISA kit is possibly including certain amount of pro-BDNF due to cross-reaction between them. There are few repots separately to measure BDNF and pro-BDNF at simultaneously. By the chronic exercise, increase of serum BDNF and decrease of serum pro-BDNF levels are reported . Therefore, the report of BDNF change by the exercise and by the supplement measured with BDNF-ELISA kit is considered not over estimated.
BMI and BDNF
Diet and BDNF
After taking enough volume of balanced meal, take a supplement to increase BDNF is recommended. As the many supplements are reported to enhance BDNF, we will introduce them with verifying the possibility. Among the many supplements, omega-3 fatty acid such as DHA, EPA and alpha-linolenic acid [35,36], and sulforaphane  an isothiocyanate present in cruciferous vegetables, curcumin [38,39] and resveratrol [40,41], kinds of polyphenolare highly probable to enhance the production of BDNF. Possible mode of action of omega-3 fatty acid is activation of Nuclear Factor Kappa B (NF-κB) levels and Cyclic AMP Response Element Binding protein (CREB), then enhancement the expression of BDNF mRNA and protein. Another pathway is to inhibit microglia release of pro-inflammatory cytokines such as Interloikin-1 Beta (IL-1β), Interloikin-6 (IL-6), Tumor Necrosis Factor (TNF), reactive oxygen species ROS and inducible form of Nitric Oxide (iNOS) through bind to peroxisome proliferator activated receptors gamma and alpha (PPARγ and PPARα) . Production of BDNF by omega-3 fatty acid implies the enhancement of neurogenesis, and the neurogenesis and production of BDNF is inhibited by the inflammation. Omega-6 fatty acid is also important for the neurogenesis, though it does not enhance BDNF production. Arachidonic acid, omega-6 fatty acid has role of maintenance of neural stem/progenitor cells pool which is differentiated and proliferated by the BDNF . Therefore, it is important to consume the ratio of omega-6 and omega-3 fatty acids as 2:1.
Curcumin, ingredient of turmeric and resveratrol, containing in grape skin and well known presents in a red wine are bioactive polyphenols and have anti-inflammatory and antioxidant properties. Both curcumin  and resveratrol  decrease expression of pro-inflammatory cytokines, such as interleukins and Tumor Necrosis Factor α (TNFα) and increase expression of BDNF levels. An expression of anti-inflammatory cytokine of interleukin 10 is enhanced by the curcumin  and resveratrol . Another polyphenol, quercetin , catechin [48,49], anthocyanin  etc., have antioxidant properties and enhance production of BDNF or BDNF signaling pathway. Carnosine and anserine are dipeptides composed with beta-alanine and histidine or methylhistidine, respectively and they present much in the avian breast having antioxidant activity . The beta-alanine dipeptides also increase secretion of BDNF acting glial cells penetrating into the brain . Supplementation of beta-alanine also increases expression of BDNF in rat  and mice  in the brain increasing carnosine production of the brain.
Sulforaphane, organosulfur compounds, widely distributed in cruciferous vegetables such as broccoli sprout and cabbages increases BDNF expression in the diabetic rats  and social defeat stress mice . Sulforaphane is well known as Nrf2 activator expressing anti-oxidant gene and simultaneously inhibit pro-inflammatory gene expression , therefore having anti-inflammatory profiles. Reduction of expression of BDNF by inflammatory cytokines is reversed by the anti-inflammatory profiles of sulforaphane. Moreover, sulforaphane is well known to have anti-carcinogenic activity in animals and humans, generating Reactivating Oxygen Species (ROS) for promoting apoptosis  and Inhibiting Histone Deacetylase (HDAC) for inhibiting telomerase activity etc., .
The developed countries including Japan become higher senior citizen’s country and the population of elderly people of over 65 years old occupy about the 1/3 of the whole population in the country. To prolong the healthy life expectancy which elderly people can make a life vigorously by themselves without caregiver’s help is relation to individual’s happiness and reduction of social security costs. We reported that “Individuals having higher serum BDNF levels have thick quadriceps muscle and is in normal and higher BMI levels, respectively”. While the BMI value of 30 and higher (Obese III) lowered the serum BDNF levels. The BDNF has properties to enhance neurogenesis and inhibition of neuronal apoptosis in the brain. It is reported that the serum contents of BDNF levels are decreased in the Alzheimer’s disease and depression. We have reviewed how can aged people to keep higher serum BDNF levels doing the exercise, taking a healthy dieting and supplements with the evidence. Although any exercise enhances the expression of BDNF in the muscle, the aerobic exercise seems more pronounced to increase BDNF than resistance exercise. In case of elderly people, higher BMI shows higher serum BDNF levels and considering the prevention of locomotive syndrome, muscle hypertrophied resistance exercise might be better among to do various exercise.
On the other hand, there is a report that BDNF controls appetite activating TrkB receptor on the dopamine 1 neuron in the ventral tegmental area projecting to hypothalamus . Furthermore, caloric restriction, 20 to 40% below the amount of calories that would be consumed ad libitum enhances expression of sirtuin gene . The caloric restriction of 20 to 40% of normal daily calorie intake is not a level to be malnutrition in usual case. The sirtuin has histone deacetylase activity, and modifies DNA stability epigenetically by enhancing histone de-acetylation. Therefore, sirtuin is so called anti-ageing gene inhibiting gene aging and inferiority by the inhibiting gene transcription. Although the caloric restriction and normal and a little bit higher BMI provides higher serum BDNF levels are contradictory, a level not to be under normal BMI (<18.4) value is required for expressing sirtuin gene and keep a considering higher serum BDNF level. Consequently, individuals are necessary higher lean body mass doing with hypertrophied resistance exercise and take a food with higher protein, vitamins with dieting fibers and appropriate supplements to enhance BDNF expression. The higher BDNF levels are good for cognition and depression, and also good for prevention of locomotor syndrome and for frailty.
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Citation: Hachisu M, Hashizume M, Kogo M, Ihara K (2019) Psychosomatic Health and Serum BDNF, Brain-Derived Neurotrophic Factor, in Elderly People. J Gerontol Geriatr Med 5: 028.
Copyright: © 2019 Mitsugu Hachisu, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.