Does Alpha-ketoglutarate Supplementation Lower BiologicaL agE in Middle- Aged Adults?

Geroscience is an emerging interdisciplinary field of study in gerontological sciences. With emphasis on understanding the mechanistic drivers of aging, it seeks translational approaches that could eventually be applied to improve human healthspan and delay age-associated chronic diseases. Contrary to popular opinion that aging is irreversible, advances in geroscience research have demonstrated that aging is modifiable and inhibiting or activating specific molecular pathways can improve healthspan and extend lifespan in model organisms. Advocates of geroscience take the view that age-related chronic diseases are best treated by slowing the aging process, rather than using the prevailing disease-centric approach of addressing each disease alone. Thus, the concept is that biological aging, rather than chronological aging, is amenable to intervention.In this regard, geroscientists are at the forefront of longevity medicine in rigorously testing novel supplements, drugs and other prophylactics that can enhance healthspan. Some of these interventions involve repurposing existing drugs such as rapamycin, a well-known immunosuppressant, at different dosing regimens to specifically target biological hallmarks of aging.This study will investigate the effects of alpha-ketoglutarate (AKG), an endogenous metabolite, on biomarkers of aging in middle-aged residents of Singapore.

Inclusion Criteria:participants whose biological age (as measured by blood DNA methylation) is greater than their chronological ageExclusion Criteria:pregnant womenmore than ONE of the following chronic medical conditions (based on the medical history and during screening), they are NOT eligible to participate in the study:Waist circumference more than or equal to 90 cm for males or more than or equal to 80 cm for femalesFasting triglycerides more than or equal to 1.7 mmol/lHigh-density lipoprotein less than 1.0 mmol/l in men or less than 1.3 mmol/l in womenBlood pressure more than or equal to 130/85 mmHg or use of antihypertensive medicationFasting glucose more than or equal to 6.0 mmol/lOsteopeniaMild Osteoarthritis not interfering in daily activitiesFatty liverParticipants will NOT be recruited if they fall in the following categories:Pre-existing, or history of major CVD (coronary artery disease, heart failure, stroke, peripheral vascular disease, pulmonary hypertension), severe/uncontrolled hypertension (under 3 or more than 3 prescribed medications), rheumatic heart disease, congenital heart disease, deep vein thrombosis, pulmonary embolismType 1 diabetes and Type 2 diabetes under oral metformin or insulin therapy and with diabetic complications such as diabetic retinopathy, diabetic nephropathyActive cancer or treatment of cancer in the last 3 yearsChronic obstructive pulmonary disease (COPD), severe asthma (taking daily medications)Pregnant women will not be recruited into this study because of the safety issues associated with X-ray irradiation during DXA scanPotential female participants who plan on pregnancy within the next 9 months of study periodMultiple sclerosis and autoimmune/immune deficiency diseases such as Rheumatic arthritis, HIV, Crohn's diseaseRecent history of sepsis or infection (within 3 months of in-patient hospitalization)Any psychiatric disease or neurodegenerative diseases such as Alzheimer's Disease, Parkinson's Disease, Lewy body dementia, and any eating disordersAny metal implants in the bodyHepatitis and Liver cirrhosis (independent of severity)Severe kidney disease (GFR less than 30 ml/min/1.73 m2)Skin disease (on oral or systemic medication for immune system)Subjects receiving any other similar investigational product within 60 days or 5 halflives before the screening, whichever that is longerAny serious medical illness which in the PI's judgment may jeopardize the subject by his or her participation in this study or may hamper his or her ability to perform and complete procedures required in the study