SC Connecticut News

The aging process affects various organs, including the heart and kidneys, leading to health issues and reduced quality of life. Despite its universality, the underlying causes of aging remain largely unknown.

Daniel Jane-Wit, MD, PhD, an associate professor of medicine (cardiovascular medicine) and immunobiology at Yale University, is exploring how certain proteins might influence aging. Supported by a grant from the American Federation for Aging Research (AFAR) and in collaboration with Yale's Y-AGE Institute and the Yale Pepper Older Americans Independence Center, Jane-Wit aims to uncover mechanisms behind aging and potential interventions.

Jane-Wit's research focuses on nine immune proteins known as complement proteins. Produced in the liver and circulating in the bloodstream, these proteins form membrane attack complexes (MACs) when activated. Traditionally studied for their role in bacterial infections, MACs were thought to cause inflammation during aging by killing cells.

"Our research found that the MAC proteins can become internalized into aging cells," Jane-Wit explained. "This overwhelms the cell’s ability to effectively cope with these proteins." The resulting protein aggregates inside cells can impair function and are linked to diseases like Alzheimer's and Parkinson's. Thus, rather than killing cells, MAC proteins may accelerate aging through aggregation.

Jane-Wit's interest in this topic stems from his background in studying solid organ transplants where complement protein activity plays a significant role. His experience treating older adults exposed to ischemic injury, trauma, and toxins also influenced his focus on how these exposures might activate complement proteins and contribute to advanced aging.

Recently published findings in Kidney International revealed that a protein called ZFYVE21, activated by complement aggregates, accelerates aging and significantly declines renal function. Jane-Wit's team is investigating how these aggregates cause inflammation and how cells detect their presence. Understanding this could lead to strategies for blocking or slowing protein aggregation.

Future research will involve collaborations within Yale and the VA to leverage resources related to aging beyond current lab capabilities. Jane-Wit hopes other researchers will validate his findings on complement's role in aging.

"I feel that complement is an underappreciated area of research," he stated. He also envisions new diagnostic strategies emerging from this work. Notably, FDA-approved drugs targeting protein aggregates for Alzheimer's disease suggest potential treatments for older patients with complement aggregates.

Acknowledging support from colleagues Drs. Eric Velazquez and Steven Pfau in Cardiovascular Medicine, Dr. Thomas Gill and Denise Acampora from the Yale Pepper Center, and Dr. Vishwa Deep Dixit of Y-AGE initiative, Jane-Wit expressed hope that contributions from Hevolution funding award recipients would advance these research centers' success.