Research Projects

Aging is a multifactorial biological process which lead to alterations in the brain structure and function, causes cognitive decline and increased susceptibility to neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and dementia. In 2019, aging related deaths contributed 23.3 million deaths globally i.e. more than cancer, diabetes, and cardiovascular diseases combined. This burden will be expected to rise significantly in India due to the shift in the poor lifestyle choices. Furthermore, this deterioration is largely driven by molecular alterations, including increased oxidative stress, accumulation of advanced glycation end-products (AGEs), neuroinflammation, and impaired proteostasis. Among these, methylglyoxal (MGO) a reactive precursor of AGEs has emerged as a key molecule implicated in accelerating brain aging. However, many studies reported that exercise is a key element in combating the age-related cognitive decline by impeding oxidative stress, inflammation and enhancing neurogenesis. However still no study is able to demonstrate the exact mechanism through which brain aging works and how exercise will reverse the cognitive decline and decrease the vulnerability of neurodegenerative disease. To address this, we will develop accelerated aging diagnostic panel on the basis of biomarkers which will be evaluated through the multimodel approach including MGO induced aging in brain organoid and animal model, Human plasma samples of different age group with different lifestyle regimen). Therefore, this novel approach not only elucidating the mechanism of brain aging but also enable prediction of the cognitive age acceleration offering early intervention strategies against neurodegenerative disease. Hypothesis of the study: We hypothesize that by developing iPSC-derived brain organoids and animal aging model via treatment with MGO (methylglyoxal) known for accelerating aging, we can assess the modulated aging biomarkers in comparison to the GlyLow treated aging model that can mimic the beneficial effects of physical activity by counteracting the cellular and molecular effects of methylglyoxal (MGO)-induced accelerated aging. Therefore, this will lead us to an understanding of the specific biomarkers that are directly related to mitigation of aging. Moreover, the human samples from different lifestyles regimens will give us more comprehensive analysis of the aging biomarkers and enables us to develop an accelerated brain aging panel and to investigate the age-related cognitive decline and neurodegenerative disease markers. Main Experiments: • Generation of iPSC-derived 3D brain organoids and induction of aging using MGO, followed by treatment with GlyLow. • Establishment of mouse models of brain aging via chronic MGO administration and physical exercise regimens; evaluation of behavioral, molecular, and histological markers. • Proteomic profiling (mass spectrometry-based) of samples from organoids, mice brains, and human plasma to identify and validate conserved aging biomarkers. • Correlation of experimental data with human lifestyle parameters to construct a diagnostic panel for brain aging. Expected Significance: If successful, this study will yield the first integrated, India-specific diagnostic panel for accelerated brain aging, with broad application in early detection and prevention of cognitive decline. It will enhance our fundamental understanding of aging mechanisms, establish novel intervention targets, and promote non-pharmacological strategies such as exercise for healthy brain aging. The project also holds translational value for personalized medicine and geriatric healthcare planning.