Healthy Aging > Research > Molecular Aging

Molecular and Cellular: Molecular Aging

A major hypothesis of aging is that oxidative processes gradually damage cellular macromolecules leading to defects in energy metabolism in mitochondria. Normal metabolic processes generate potentially deleterious reactive oxygen species leading to oxidative damage and inflammation, which increase with age and may contribute to senescence. Aging is associated with low-grade elevation of circulating inflammatory cytokines, which leads to disease-associated morbidity and mortality. However, it is presently unclear whether chronic inflammation is a consequence of deregulation of the immune system in older individuals or if it is a consequence of increased cell stress and cellular senescence.

We are studying oxidative stress using various model systems and approaches, one of which exploits human progeroid diseases, such as Werner's syndrome, Cockayne syndrome and Sjøgrens syndrome, that are characterized by premature aging. We are examining whether oxidation and inflammation are particularly prominent and whether cellular stress causes major increases in aging-related parameters. This is done by examining oxidation of DNA and other macromolecules and by measuring mitochondrial functions such as respiration and energy output in cell lines and in cells and materials from individuals affected by a progeroid disease or normal controls.

A clinical protocol was developed for studying these parameters in blood samples obtained from the Copenhagen Aging and Midlife Biobank (CAMB) cohort, which is associated with the CEHA center. This cohort, and additional studies of this cohort, are described in research Program 3. We are asking whether cellular oxidation increases with aging and whether it is significantly increased in patients with frailty and cognitive deficiencies, which are clinical entities associated with aging. We will coordinate our studies with MRI scanning studies performed in Program 1b and muscle function studies in Program 2. These studies encompass molecular, clinical and epidemiological approaches.