Dr Rajkumar s/o Dorajoo Image

Dr Rajkumar s/o Dorajoo

Senior Research Scientist Laboratory of Metabolic Disease & Ageing Genomics Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR)

Rajkumar s/o Dorajoo is a Senior Research Scientist at the Genome Institute of Singapore (GIS) and leads the Laboratory of Metabolic Diseases and Ageing Genomics. He is also the PI of the genetics sub-cohort of the Singapore Chinese Health Study, a collection of over 25,000 local Singaporean Chinese participants with rich genetic data and extensive longitudinal data on age-related traits and health outcomes that have been curated for over 25 years. His work has been tailored towards using a breath of genomic data to understand biological processes of accelerated ageing and understanding how genetic predispositions and lifestyle exposures, earlier in life, impacts upon age-related health outcomes, later in life.

PHOM 2024 Talk details

Midlife Obesity and Mobility Dysfunction in Late Life

Human life expectancy has increased remarkably over the last two centuries. Although we live longer, this is often not matched by healthy life expectancy, indicating that an increasing proportion of old age may be lived in poor health. How exposures such as obesity levels, earlier in life, predisposes to subsequent adverse health outcomes is not well understood, especially in Asian populations. In this talk, I’ll present data that indicates on the pernicious effects of excess weight on mobility dysfunction. We evaluated genetic predispositions for body mass index (BMI) in 8,342 Singapore Chinese participants from the Singapore Chinese Health Study, who were followed up from measurement of BMI at midlife (average 53 years), to measurements of Timed Up-and-Go (TUG) test (as a functional mobility measure) 20 years later. A robust 75.83% of genetically determined BMI effects on TUG was mediated through midlife BMI (P = 9.24×10-21). Utilizing Mendelian randomization, we demonstrated a causal effect between BMI and functional mobility (P = 0.001). Secondary gene enrichment evaluations highlighted down-regulation of genes at BMI risk loci that were correlated with poorer functional mobility in the substantia nigra and amygdala regions as compared to all other tissues. These genes also exhibit differential expression patterns during human brain development. In sum, our data highlights that midlife obesity impacts on mobility dysfunction later in life and suggests potential overlap of neuronal pathways that regulate predispositions to obesity and mobility dysfunction.