A research team led by experts from Brock University has discovered an immunotherapy that can enhance the health span of naturally aged mice and extend their lifespan by reducing chronic inflammation.
Chemical Processes Involved in Aging
Aging is a complex process that involves a decline in key biological functions that result in increased susceptibility to chronic diseases and reduced lifespan. It was previously believed that at the molecular level, aging is supported by progressive biomolecular damage caused by degenerative protein modifications (DPMs). These include glycation, deamidation, oxidation, and other non-enzymatic structural changes.
Modern technology has allowed scientists to recognize that aging results from deleterious chemical processes that impair biomolecules and damage the homeostatic functions programmed by our DNA. However, it remains unclear whether therapeutic targeting of the damaged biomolecules effectively maintains tissue function and extends a healthy lifespan.
The functional impact of DPMs depends on the mode of modification and the target molecule involved. However, "gain of function structural changes caused by DPMs could play equally important roles in human pathology.
READ ALSO: Age and Environment Influence Gene Expression More Than Genetics as a Person Gets Older
Anti-isoDGR Immunotherapy
An international research team has discovered an immunotherapy that has the potential to add years to healthy aging. In the study "Immunotherapy targeting isoDGR-protein damage extends lifespan in a mouse model of protein deamidation", the experts introduced an innovative method that addresses health issues arising from poor lifestyle choices that can damage biomolecules and contribute to developing diseases later in life.
Health Sciences professor Newman Sze led the research. As Canada Research Chair, he studies diseases people experience as they age, particularly those related to the brain and damaged blood vessels. His laboratory has developed new methods that study the deterioration of body tissues over time and created new drugs that help the immune system eliminate abnormal biomolecules.
Environmental stresses and physiological conditions can cause biomolecular damage in tissues. One such change is called isoDGR (isoAsp-Gly-Arg) which triggers chronic inflammation in the body, resulting in tissue degeneration. The accumulation of isoDGR has been recognized as a "molecular clock" of aging, but the benefits of targeting these structures with specific immunotherapies remain unknown.
Sze and his colleagues developed monoclonal antibodies known as isoDGR-mAb. They are laboratory-engineered proteins designed to boost the ability of the immune system to attack abnormal molecules or unhealthy cells. The approach involves directing the immune system to clear out accumulated proteins damaged by stress, unhealthy diets, inactive lifestyles, and genetic factors that cause aging and age-related diseases.
Using animal models, it was found that treatment with isoDGR-mAb doubled the subjects' lifespan and preserved their behavior and coordination functions. Additionally, the monoclonal drug reduced the level of pro-inflammatory cytokine in the circulation and body tissues.
Existing treatments for age-related diseases mainly focus on symptoms. The pioneering mAb by Sze and his team uniquely targets the root causes of chronic diseases to extend the human health span substantially.
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