The Aging GABAergic System and Its Nutritional Support

Abstract

Aging is associated with a decline in hormones and an associated decline in GABAergic function and calcium and ion current dysregulation. Neurosteroid hormones act as direct calcium channel blockers, or they can act indirectly on calcium channels through their interaction with GABA receptors. The calcium channel dysfunction associated with hormone loss further leads to an excitatory cell state, which can ultimately lead to cell death. The calcium theory of aging posits that cellular mechanisms, which maintain the homeostasis of cytosol Ca2+ concentration, play a key role in brain aging and that sustained changes in Ca2+ homeostasis provide the final common pathway for age-associated brain changes. There is a link between hormone loss and calcium dysregulation. Loss of calcium regulation associated with aging can lead to an excitatory cell state, primarily in the mitochondria and nerve cells, which can ultimately lead to cell death if not kept in check. A decline in GABAergic function can also be specifically tied to declines in progesterone, allopregnanolone, and DHEA levels associated with aging. This decline in GABAergic function associated with hormone loss ultimately affects GABAergic inhibition or excitement and calcium regulation throughout the body. In addition, declines in GABAergic function can also be tied to vitamin status and to toxic chemicals in the food supply. The decline in GABAergic function associated with aging has an effect on just about every body organ system. Nutritional support of the GABAergic system with supportive foods, vitamins, and GABA or similar GABA receptor ligands may address some of the GABAergic dysfunction associated with aging.

γ-Aminobutyric acids (GABA) and serum GABA/AABA (G/A) ratio as potential biomarkers of physical performance and aging

“…GABA possesses an excitatory effect mediated by GABA-A receptors, while activation of presynaptical GABA-B receptors impedes opening of voltage-activated Ca 2+ channels and reduces neurotransmitter release, thus GABA can inhibit its own release through a negative feedback loop via GABA-B receptors present on GABAergic axons (31). This dual action of GABA could be dose-dependent and inhibitory at low concentrations and excitatory to some GABA receptors at higher concentrations (32). Currently most studies on aging -related GABA changes focus on altered brain GABA levels (33,34), while the associations between circulating GABA levels, age, and aging-related physical performance are seldom reported.…”

“…Exercise can increase myo ber size, whole muscle mass, muscle quality, and attenuates age-related decreases in muscle strength (8). Elevated GABA level in serum induced by physical activity may help enhance muscle hypertrophy, then assist muscle growth and maintain the physical performance during aging, and GABA also plays key roles in maintaining optimal muscle tonicity (32).…”

“…To be included in the current analyses, individuals needed to be 20-85 years of age, self-reported white and non-Hispanic, and without a self-reported major chronic disease. Individuals within each sex and each 15 year age group (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)35-50, 50-65, and 65+ yrs) were ranked for their performance on the FIT Core's hand grip strength test and test of the number of chair stands completed in 30 seconds. The 5 individuals within each sex and age range with the lowest, average, and highest composite rank were selected and grouped as low (LP), average (AP), and high (HP) performers, respectively (Table 1).…”

Recent advances in the biosynthesis and industrial biotechnology of Gamma-amino butyric acid

“…It plays a crucial inhibitory function within the central nervous system (Patten et al 2016 ). Collectively, these diverse mechanisms highlight the significant impact of GABA on cardiovascular health, particularly in addressing the complex challenges associated with cardiovascular conditions in aging populations (Mills 2021 ).…”

Neuronal C/EBPβ/AEP pathway shortens life span via selective GABAnergic neuronal degeneration by FOXO repression

“…Furthermore, C/EBPβ is age-dependently up-regulated in hippocampal neurons, implicated in neurogenesis and excitotoxicity ( 24 , 25 ). GABAnergic (Gamma-Aminobutyric Acid-nergic) neurons are the most important negative regulator in excitatory and inhibitory balance in aging and AD ( 26 , 27 ). To better understand the mechanism how neuronal C/EBPβ/AEP signaling contributes to life span, we generated neuronal specific Thy1-human C/EBPβ Tg mice and neuronal specific cebp-2 and lgmn-1 overexpression worms.…”