Relation of DNA methylation and molecular markers to health and well-being in aging

Awardee Recipient

  • Olivia Okereke, MD, MS

    Olivia Okereke, MD, MS

    Olivia Okereke, MD, MS is a Board-certified geriatric psychiatrist and Associate Professor of Psychiatry and Associate Professor of Epidemiology at Harvard Medical School and the Harvard T. H. Chan School of Public Health.  She is Director of...

Award

  • 2016 - Pilot Grant

Background and Significance

Knowledge gaps exist regarding the biological mechanisms that are involved in trajectories of health and aging. DNA methylation – the addition of a methyl group to the CpG dinucleotide – is an epigenetic mechanism involved in switching genes on and off (gene expression), and it may provide critical insights regarding mechanisms in stress and aging. Epigenetic (meaning “above genetic”) regulation by DNA methylation (covalent addition of a methyl group to the C-5 position of a cytosine base in the 5’-CG’3’ or CpG sequence context) induces mitotically heritable alterations in gene expression without modification of the DNA sequence. Changes in DNA methylation within CpG dinucleotides may represent biological mechanisms that mediate the effects of age on chronic disease and may also provide an explanatory biologic link between psychosocial stress and health outcomes in aging. We hypothesize that psychosocial stress may accelerate cellular aging and may be associated with changes in DNA methylation, which we hypothesize will be correlated with two other molecular markers of aging – telomere length and mitochondrial DNA copy number.

Specific Aims

  1. To obtain DNA methylation markers in a well-characterized, in-clinic sample of participants and to evaluate correlations of DNA methylation with other molecular markers (telomere length [TL] and mitochondrial DNA copy number [mtCN]).
  1. To evaluate relations of psychological and social stress to DNA methylation at CpG dinucleotides.

In Aim 1, we hypothesize that the epigenetic (DNA methylation) and genetic markers of aging (TL and mtCN) will be positively correlated. In Aim 2, we hypothesize that higher burden of psychosocial stress factors (determined by higher index of depressive symptoms, anxiety, low social support and caregiving strain) will be related to epigenetic acceleration of aging. Using candidate epigenetic biomarkers of aging based on DNA methylation (DNAm) levels – a DNAm age concept developed and applied previously by Horvath – we will conduct a novel examination of the associations of DNAm with both TL and mtCN.

 

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Outcomes

The Osher Pilot Grant directly resulted in new funding from the NIH:

Title: Neuropsychiatric symptoms, cognitive aging and DNA methylation age in the VITAL-DEP cohort
Grant Number: 3 R01 MH091448-09S1
Funding agency: NIH/NIMH
Total Award: $341,815