Metabolon Mines Data for Causes of Frailty in the Elderly

Maggie Kuhn, founder of the Gray Panthers movement, famously said that one of the myths about old age is that it’s a disease. It isn’t. Another is that elderly people are all alike. They aren’t.

Some people age with relative ease, while others become medically frail. They lose strength, fatigue more easily, or their health, social and psychological challenges accumulate, and they must depend on others for assistance with activities of daily living.

Metabolon, a Morrisville-based precision health company specializing in a technology called metabolomics, is teaming with three Canadian research groups to discover humans’ frailty biomarkers, determine the severity of frailty and what can be done to help avoid the condition.

Together, they’re developing a $4 million longitudinal research program to perform large-scale metabolomic profiling and biomarker identification on samples from Canada’s largest and most comprehensive study on aging.

Metabolomics is the large-scale study of small molecules, commonly known as metabolites, within cells, biofluids, tissues or organisms. Collectively, the biochemistry of these small molecules and their interactions within a biological system are known as the metabolome. Metabolon’s proprietary Precision Metabolomics technology provides researchers with the ability to profile a subject’s or patient’s metabolome for applications in precision medicine and to advance understanding of the metabolic basis of disease, disease progression and treatment mechanisms.

The goal of this project is to develop a research program to understand the influence of the metabolome, microbiome, genes, diet, lifestyle and drug treatments on the health and well-being of aging populations.

This is one of many large population health studies to use metabolomics to get at the causes, predictors and progression of disease through genomics and biomarkers and accelerate precision medicine, said Rohan F. Hastie, Ph.D., president and CEO of Metabolon.

Hastie cited the 2015 launch of the Precision Medicine Initiative, which is enrolling 3 million participants in the U.S., a third of whom are military veterans seeking care in the Veterans Administration health system for the Million Veteran Program (MVP). The MVP is employing Metabolon’s technology. Another study in the U.K. is enrolling 500,000 participants.

Frailty Prevalence and Impact

The prevalence of medically frail older adults varies by which definitions are used. By one estimate, more than 1 million older Canadians are medically frail, or more than 25% of Canadians aged 65 to 84, and over 50% over the age of 85. By 2025, estimates are that more than 2 million Canadians will be living with frailty.

In the U.S., the population of adults ages 65 and over is projected to nearly double from 51 million in 2017 to 95 million by 2060. Therefore, insights from this study and future research based upon it has important applications here as well.

Frailty also impacts family and friend caregivers and places large burdens on health and social care systems to meet the growing demand.

Mechanics of the Study

The other partners in the project are:

Canadian Frailty Network (CFN), Canada’s sole network devoted to improving care for older Canadians living with frailty and their families;

Canadian Longitudinal Study on Aging (CLSA), a national research platform on aging involving 50,000 men and women in Canada;

McMaster Institute for Research on Aging (MIRA) at McMaster University, which seeks to optimize the health and longevity of the aging population through leading-edge research, education and stakeholder collaborations.

CLSA will soon initiate analysis on 10,000 blood samples to establish baseline metabolomic measures. This will allow researchers to identify metabolites that will help to improve not only early prediction of frailty, but also lead to further research on treatments addressing specific aspects of frailty.

CLSA participants will undergo waves of data collection every three years and be followed for 20 years or until death. The last cycle of data collection will finish in 2033, said Parminder Raina, Ph.D., professor in the Department of Health Research Methods, Evidence and Impact at McMaster, lead principal investigator of the CLSA and scientific director of MIRA.

“CFN’s mission is to improve care for older Canadians to avoid or live with frailty,” said John Muscedere, M.D., scientific director of CFN and a professor of critical care medicine at Queen’s University/Kingston Health Sciences Centre. “Our work is based on creating scientific evidence that can be translated into practices and policies to avoid or delay frailty.”

Metabolomics Provides Broader View

“Historically, people have looked at the genetics and thought that was enough,” said Metabolon’s Hastie. “People are realizing now that you need to understand the biochemistry. You need to understand the metabolite profile and metabolism of these patients to see how they can go on and develop disease.” He noted that recently the U.K.’s National Health Service classified obesity as the greater cause of some cancers than smoking.

Metabolomics has a huge role to play in a systems approach to studying disease, he said.

“What makes this partnership so powerful is that it is a longitudinal study,” said Greg Michelotti, Ph.D., scientific director of Metabolon. “Many of the large population health studies out there are cross-sectional, from one time point. The CLSA is powerful in that it is one of the largest studies conducting longitudinal sampling of the population. We will be able to see changes over time.”

“Your genome is your genome. It doesn’t change. It’s the biochemical processes within an individual that are what are changing over time. You need to be able to follow a patient over a long period of time to see how a disease is progressing,” added Hastie.

Interestingly, though the technology to mine the data of the metabolome has advanced with recent innovations in big data analysis, scientists have been studying the metabolome for over 140 years, said Michelotti.

About Metabolon

Metabolon was founded in 2000 and has 200 employees, including nearly 40 who have Ph.D.s from diverse backgrounds in data science, molecular biology and biochemistry, and a staff of statistics, bioinformatics, healthcare, chemistry and software development experts, according to its website. Previously chief business officer at Metabolon, Hastie was named CEO a year ago following the retirement of co-founder John Ryals, Ph.D. Hastie said Metabolon has already been working on similar projects of this type about which the company will make public announcements in the coming months.