Gene P. Ables, Ph.D.
Dr. Ables received his degree of Doctor of Veterinary Medicine from the University of the Philippines. He then obtained his PhD from Hokkaido University (Japan). His post-doctoral research in Preventive Medicine and Nutrition at Columbia University focused on liver lipid metabolism. In 2006, he was appointed Associate Research Scientist at the Columbia University Medical Center. Dr. Ables joined OFAS in April 2011 as a Senior Scientist, and in 2015 he was appointed Associate Science Director. He leads staff in investigations of the methionine-restricted diet’s effects on metabolism, cancer, and epigenetics.
Our studies have demonstrated that a sulfur amino acid-restricted (SAAR) diet protects mice against fatty liver disease, obesity, and diabetes, does not affect cardiac function, and attenuates kidney injury, but reduces bone mass (Ables et al., 2015; Ables et al., 2012; Cooke et al., 2020; Cooke et al., 2018; Ouattara et al., 2016). Compared to their control-fed (CF) counterparts, the circulating profile of SAAR rodents indicates reduced glucose, insulin, IGF-1, and leptin, while adiponectin and FGF21 are elevated (Ables et al., 2015; Cooke et al., 2020; Malloy et al., 2006). In addition, we have also identified the molecular mechanisms by which a SAAR diet confers protection in the age-related disease models we have tested. For example, protection against fatty liver disease in mice fed a high-fat SAAR diet could be explained by upregulated glucose-sensitizing hepatic Pparg and Fgf21 genes and downregulated Scd1 gene (Ables et al., 2012). In addition, SAAR attenuated kidney injury in mice by downregulating renal genes that are involved during inflammation and fibrosis, such as Tnfa and Fn1, respectively (Cooke et al., 2018). Most recently, we demonstrated that reduced adipose tissue mass in obese mice activate autophagy independent of the actions of adiponectin and FGF21 (Cooke et al., 2020).
Dr. Ables continues to investigate the effects of SAAR on neurodegenerative diseases using a mouse model for amyotrophic lateral sclerosis amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease. ALS is a progressive and fatal neuromuscular disease characterized by neuroinflammation progressing to neurodegeneration. No cure for ALS has yet been identified, and there is a dearth of proven useful therapeutic interventions. One of the causes of neuronal death in ALS is oxidative damage, something SAAR in rodents has shown to beneficially effect. However, the effect of SAAR on neurological systems using a mouse disease model such as ALS has not yet been examined. To investigate this, Dr. Ables’s lab is conducting experiments on transgenic mice transfected with the ALS-associated G93A human superoxide dismutase 1 mutation, SOD1-G93A. They are in the process of analyzing data on the mechanisms by which SAAR effects the onset of disease, measured by various strength and agility tests. They are also analyzing whether SAAR suppresses disease progression by attenuation of inflammation and oxidative stress markers in neurons and muscle cells. Characterization of the effects of SAAR in SOD1-G93A mice is the first step that will direct future investigations of how SAAR may affect other neurological diseases.
D.V.M. University of the Philippines
- Sulfur Amino Acid-Restricted Diets: Mechanisms and Health Benefits
Encyclopedia of Biological Chemistry III (Third Edition) 2021; : 105-13| PubMed ID: Weight loss and concomitant adipose autophagy in methionine-restricted obese mice is not dependent on adiponectin or FGF21
Cooke D, Mattocks DAL, Nichenametla SN, Anunciado-Koza RP, Koza RA, Ables GP
Obesity 2020; 28 (6): 1075-1085| PubMed ID: 32348021Dietary methionine influences therapy in mouse cancer models and alters human metabolism.
Gao X, Sanderson SM, Dai Z, Reid MA, Cooper DE, Lu M, Richie JP Jr, Ciccarella A, Calcagnotto A, Mikhael PG, Mentch SJ, Liu J, Ables G, Kirsch DG, Hsu DS, Nichenametla SN, Locasale JW
Nature 2019; 572 (7769): 397-401| PubMed ID: 31367041Bone marrow adiposity: basic and clinical implications
Sebo ZL, Rendina-Ruedy E, Ables GP, Lindskog DM, Rodeheffer MS, Fazeli PK, Horowitz MC
Endocrine Reviews 2019; 40 (5): 1187-1206| PubMed ID: 31127816Identification and application of gene expression signatures associated with lifespan extension
Tyshkovskiy A, Bozaykut P, Borodinova AA, Gerashchenko MV, Ables GP, Garratt M, Khaitovich P, Clish CB, Miller RA, Gladyshev VN.
Cell Metabolism 2019; 30 (3): 573-593.e8| PubMed ID: 31353263 Bone marrow adipocytes.
Horowitz MC, Berry R, Holtrup B, Sebo Z, Nelson T, Fretz JA, Lindskog D, Kaplan JL, Ables GP, Rodeheffer MS, Rosen CJ.
Adipocytes 2017; 6 (3): 193-204| PubMed ID: 28872979Dietary methionine restriction modulates renal response and attenuates kidney injury in mice
Cooke D, Ouattara A, Ables GP
The FASEB Journal 2017; 32 (2): 693-702| PubMed ID: 28970255Pleiotropic responses to methionine restriction
Ables GP, Johnson JE
Experimental Gerontology 2017; (94): 83-88| PubMed ID: 28108330Methionine restriction alters bone morphology and affects osteoblast differentiation
Ouattara A, Cooke D, Gopalakrishnan R, Huang TH, Ables GP
Bone Reports 2016; 5: 33-42| PubMed ID: 28326345Methionine restriction beyond life-span extension
Ables GP, Hens JR, Nichenametla SN
Annals of the New York Academy of Sciences 2016; 1363 (1): 68-79| PubMed ID: 26916321Dietary restrictions, bone density, and bone quality
Huang TH, Ables GP
Annals of the New York Academy of Sciences 2016; 1363 (1): 26-39| PubMed ID: 26881697Histone methylation dynamics and gene regulation occur through the sensing of one-carbon metabolism
Mentch SJ, Mehrmohamadi M, Huang L, Liu X, Gupta D, Mattocks D, Gόmez Padilla P, Ables G, Bamman MM, Thalacker-Mercer AE, Nichenametla SN, Locasale JW
Cell Metabolism 2015; 22 (5): 861-73| PubMed ID: 26411344Effects of methionine restriction and endurance exercise on bones of ovariectomized rats: a study of histomorphometry, densitometry, and biomechanical properties
Huang TH, Su IH, Lewis JL, Chang MS, Hsu AT, Perrone CE, Ables GP
Journal of Applied Physiology (Bethesda, Md. : 1985) 2015; 119 (5): 517-26| PubMed ID: 26159761Dietary methionine restriction in mice elicits an adaptive cardiovascular response to hyperhomocysteinemia
Ables GP, Ouattara A, Hampton TG, Cooke D, Perodin F, Augie I, Orentreich DS
Scientific Reports 2015; 5: 8886| PubMed ID: 25744495A methionine-restricted diet and endurance exercise decrease bone mass and extrinsic strength but increase intrinsic strength in growing male rats
Huang TH, Lewis JL, Lin HS, Kuo LT, Mao SW, Tai YS, Chang MS, Ables GP, Perrone CE, Yang RS
The Journal of Nutrition 2014; 144 (5): 621-30| PubMed ID: 24647387The First International Mini-Symposium on Methionine Restriction and Lifespan
Ables GP, Brown-Borg HM, Buffenstein R, Church CD, Elshorbagy AK, Gladyshev VN, Huang TH, Miller RA, Mitchell JR, Richie JP, Rogina B, Stipanuk MH, Orentreich DS, Orentreich N
Frontiers in Genetics 2014; 5: 122| PubMed ID: 24847356Methionine restriction prevents the progression of hepatic steatosis in leptin-deficient obese mice
Malloy VL, Perrone CE, Mattocks DA, Ables GP, Caliendo NS, Orentreich DS, Orentreich N
Metabolism: Clinical and Experimental 2013; 62 (11): 1651-61| PubMed ID: 23928105Intestinal DGAT1 deficiency reduces postprandial triglyceride and retinyl ester excursions by inhibiting chylomicron secretion and delaying gastric emptying
Ables GP, Yang KJ, Vogel S, Hernandez-Ono A, Yu S, Yuen JJ, Birtles S, Buckett LK, Turnbull AV, Goldberg IJ, Blaner WS, Huang LS, Ginsberg HN
Journal of Lipid Research 2012; 53 (11): 2364-79| PubMed ID: 22911105Update on pparγ and nonalcoholic Fatty liver disease
PPAR Research 2012; 2012: 912351| PubMed ID: 22966224Methionine-restricted C57BL/6J mice are resistant to diet-induced obesity and insulin resistance but have low bone density
Ables GP, Perrone CE, Orentreich D, Orentreich N
PloS One 2012; 7 (12): e51357| PubMed ID: 23236485DGAT1 deficiency decreases PPAR expression and does not lead to lipotoxicity in cardiac and skeletal muscle
Liu L, Yu S, Khan RS, Ables GP, Bharadwaj KG, Hu Y, Huggins LA, Eriksson JW, Buckett LK, Turnbull AV, Ginsberg HN, Blaner WS, Huang LS, Goldberg IJ
Journal of Lipid Research 2011; 52 (4): 732-44| PubMed ID: 21205704Hepatic overexpression of hormone-sensitive lipase and adipose triglyceride lipase promotes fatty acid oxidation, stimulates direct release of free fatty acids, and ameliorates steatosis
Reid BN, Ables GP, Otlivanchik OA, Schoiswohl G, Zechner R, Blaner WS, Goldberg IJ, Schwabe RF, Chua SC Jr, Huang LS
Journal of Biological Chemistry 2008; 283 (19): 13087-99| PubMed ID: 18337240Genetic polymorphisms and antiviral activity in the bovine MX1 gene
Nakatsu Y, Yamada K, Ueda J, Onogi A, Ables GP, Nishibori M, Hata H, Takada A, Sawai K, Tanabe Y, Morita M, Daikohara M, Watanabe T
Animal Genetics 2004; 35 (3): 182-7| PubMed ID: 15147388Sequence analysis of the NRAMP1 genes from different bovine and buffalo breeds
Ables GP, Nishibori M, Kanemaki M, Watanabe T
Journal of Veterinary Medical Science 2002; 64 (11): 1081-3| PubMed ID: 12499702Analysis of genetic factors associated with nitric oxide production in mice
Ables GP, Hamashima N, Watanabe T
Biochemical Genetics 2001; 39 (11-12): 379-94| PubMed ID: 11860201Male hybrid sterility of mice with the genomic region of the KitW mutation and the KitS allele from Mus spretus
el-Shazly S, Seo KW, el-Nahas A, Ables GP, Asano A, Watanabe T
Biochemical Genetics 2001; 39 (3-4): 127-37| PubMed ID: 11860201The roles of Nramp1 and Tnfa genes in nitric oxide production and their effect on the growth of Salmonella typhimurium in macrophages from Nramp1 congenic and tumor necrosis factor-alpha-/- mice
Ables GP, Takamatsu D, Noma H, El-Shazly S, Jin HK, Taniguchi T, Sekikawa K, Watanabe T
Journal of Interferon & Cytokine Research 2001; 21 (1): 53-62| PubMed ID: 11177581