These studies have provided evidence that α-ketoglutarate contributes to regulating: kidney function;[7] the benefits that resistance exercise has in reducing obesity, strengthening muscles, and preventing muscle atrophy;[8] glucose tolerance as defined in glucose tolerance tests;[9] aging and the development of changes that are associated with aging including old age-related disorders and diseases;[10] the development and/or progression of certain types of cancer and inflammations;[11] and the differentiation of immature T cells into mature T cells.

Additionally, α-ketoglutarate increases the activity of superoxide dismutase, which converts the highly toxic (O−2) radical to molecular oxygen (i.e., O2) and H2O2.

[4][5] A study conducted on the GABAergic neurons (i.e., nerve cells) in the neocortex of rat brains reported that the cytosolic form of the aspartate transaminase enzyme metabolizes α-ketoglutarate to glutamate which in turn is metabolized by glutamic acid decarboxylase to the inhibitory neurotransmitter gamma-aminobutyric acid.

To make this distinction, studies have shown that the action of an OXGR1-activating agent on cultured cells, cultured tissues, or animals does not occur or is reduced when these cells, tissues, or animals have been altered so that they do not express or express greatly reduced levels of the OXGR1 protein,[18][19][20][22] or when their actions are inhibited by an OXGR1 receptor antagonists.

This study also showed that the α-ketoglutarate in the blood of mice filtered through their kidney's glomeruli into the proximal tubules and loops of Henle where it was reabsorbed.

[24] Another study showed that a) In silico computer simulations strongly suggested that α-ketoglutarate bound to mouse OXGPR1; b) suspensions of canal duct cells isolated from the collecting ducts, loops of Henle, vasa recta, and interstitium of mouse kidneys raised their cytosolic ionic calcium, i.e., Ca2+ levels in response to α-ketoglutarate but this response (which is an indicator of cell activation) was blocked by pretreating the cells with Montelukast; and c) compared to mice not treated with streptozotocin, streptozotocin-induced diabetic mice (an animal disease model of diabetes) urinated only a small amount of the ionic sodium (Na+) that they drank or received by intravenous injections; Montelukast reversed this defect in the streptozotocin-pretreated mice.

[22] These results indicate that in mice: a) α-ketoglutarate stimulates kidney OXGR1 to activate pendrin-mediated reabsorption of sodium and chloride by type B and non-A–non-B intercalated cells; b) high alkaline (i.e., sodium bicarbonate) intake produces significant increases in urine pH and α-ketoglutarate levels and impairs secretion of bicarbonate into the CDS tubules' lumens; c) the acid–base balance (i.e., levels of acids relative to their bases) in the face of high alkali intake depends on the activation of OXGR1 by α-ketoglutarate;[7][24] d) alkaline loading directly or indirectly stimulates α-ketoglutarate secretion into the kidney's proximal tubules where further down these tubules it activates OXGR1 and thereby the absorption and secretion of various agents that contribute to restoring a physiologically normal acid-base balance;[24] and e) α-ketoglutarate stimulates OXGR1-bearing CDS cells to raise their levels of cytosolic Ca2+) and in diabetic mice (and presumably other conditions involving high levels of blood and/or urine glucose) to increase these cells uptake of Na+.

These findings indicate that in mice resistance exercise increases muscle production as well as serum levels of α-ketoglutarate which in turn suppresses diet-induced obesity (i.e., low body fat and high lean body masses) at least in part by stimulating the OXGR1 on adrenal gland chromaffin cells to release epinephrine.

This study indicates that α-ketoglutarate regulates body fat mass and insulin sensitivity in rats as well as mice.

α-Ketoglutarate has been reported to increase the life span and/or delay the development of old age-related diseases in a species of roundworms and in mice.

It nearly doubled the life span and delayed age-related deteriorations (e.g., decline in rapid, coordinated body movements) of Caenorhabditis elegans roundworms when added to their cell cultures.

[3][28] Similarly, mice fed a diet high in calcium-bound α-ketoglutarate had a longer life span and shorter length of time in which they suffered old age-related morbidities (e.g., increased frailty, hair loss, and changes in body weight).

Assays (termed epigenetic clock tests) that determine the presence of methylations of cystines in CpG islands for genes have been used to define an individual's biological age.

[15][33] Overall, the combined group of males and females showed an average fall in biological age of 8 years compared to before treatment.

This superfamily consists of two groups, the FAD-dependent amine oxidases which do not require α-ketoglutarate for activation and the Fe2+/α-ketoglutarate-dependent dioxygenases (Fe2+ is the ferrous form of iron, i.e., Fe2+).

They function as dioxygenases or hydroxylases to remove methyl groups from the lysine residues on the histones enveloping DNA and thereby alter the expression of diverse genes.

These demethylations have a variety of effects including, similar to the Fe2+/α-ketoglutarate-dependent dioxygenases, alteration of the development and/or progression of various cancers, immune responses, and other disorders (see functions of TET enzymes).