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Microbes and Metabolites Fuel an Ambitious Aging Project

Craig Venter’s new company wants to improve human longevity by creating the world’s largest, most comprehensive database of genetic and physiological information.

Last week, genomics entrepreneur Craig Venter announced his latest venture: a company that will create what it calls the most comprehensive and complete data set on human health to tackle diseases of aging.

Human Longevity, based in San Diego, says it will sequence some 40,000 human genomes per year to start, using Illumina’s new high-throughput sequencing machines (see “Does Illumina Have the First $1,000 Genome?”). Eventually, it plans to work its way up to 100,000 genomes per year. The company will also sequence the genomes of the body’s multitudes of microbial inhabitants, called the microbiome, and analyze the thousands of metabolites that can be found in blood and other patient samples.

By combining these disparate types of data, the new company hopes to make inroads into the enigmatic process of aging and the many diseases, including cancer and heart disease, that are strongly associated with it. “Aging is exerting a force on humans that is exposing us to diseases, and the diseases are idiosyncratic, partly based on genetics, partly on environment,” says Leonard Guarente, who researches aging at MIT and is not involved in the company. “The hope for many of us who study aging is that by having interventions that hit key pathways in aging, we can affect disease.”

But despite decades of research on aging and age-related diseases, there are no treatments to slow aging, and diseases like cancer, heart disease, and Alzheimer’s continue to plague patients. A more comprehensive approach to studying human aging could help, says Guarente. The key is to go beyond genome sequencing by looking at gene activity and changes in the array of proteins and other molecules found in patient samples.

To that end, Human Longevity will collaborate with Metabolon, a company based in Durham, North Carolina, to profile the metabolites circulating in the bloodstreams of study participants. Metabolon was an early pioneer in the field of metabolomics, which catalogues the amino acids, fats, and other small molecules in a blood or other sample to develop more accurate diagnostic tests for diseases (see “10 Emerging Technologies 2005: Metabolomics”).

Metabolon uses mass spectrometry to identify small molecules in a sample. In a human blood sample, there are around 1,200 different types; Metabolon’s process can also determine the amount of each one present. While genome sequencing can provide information about inherited risk of disease and some hints of the likelihood that a person will have a long life, metabolic data provides information on how environment, diet, and other features of an individual’s life affect health.

Metabolic data can also help researchers interpret the results of genome-based studies, which can often pinpoint a particular gene as important in a disease or a normal cellular process without clarifying what that gene actually does. If a particular metabolite is found to correlate with a particular genetic signal in a study, then researchers have a clue as to the function of the DNA signal.

And changes in blood metabolites are not just caused by changes in human cell behavior: the microbes that live in our bodies produce metabolites that can be detected in blood, says John Ryals, CEO and founder of Metabolon. “When you get certain diseases, we believe your gut microbiome is changing its composition, and that leads to changes in what molecules are being made,” he says.

Ryals says his company, working with collaborators, has already shown that blood biochemistry changes with aging: “You can tell how old someone is just by looking at their metabolites.”

Human Longevity says it will license information from its databases to pharmaceutical and biotechnology companies as well as academics.

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