Comprehensive study finds 238 genes that affect aging in yeast cells

October 8, 2015
A depiction of the double helical structure of DNA. Its four coding units (A, T, C, G) are color-coded in pink, orange, purple and yellow. Credit: NHGRI

Following an exhaustive, ten-year effort, scientists at the Buck Institute for Research on Aging and the University of Washington have identified 238 genes that, when removed, increase the replicative lifespan of S. cerevisiae yeast cells. This is the first time 189 of these genes have been linked to aging. These results provide new genomic targets that could eventually be used to improve human health. The research was published online on October 8th in the journal Cell Metabolism.

"This study looks at aging in the context of the whole genome and gives us a more complete picture of what aging is," said Brian Kennedy, PhD, lead author and the Buck Institute's president and CEO. "It also sets up a framework to define the entire network that influences aging in this organism."

The Kennedy lab collaborated closely with Matt Kaeberlein, PhD, a professor in the Department of Pathology at the University of Washington, and his team. The two groups began the painstaking process of examining 4,698 yeast strains, each with a single gene deletion. To determine which strains yielded increased lifespan, the researchers counted , logging how many daughter cells a mother produced before it stopped dividing.

"We had a small needle attached to a microscope, and we used that needle to tease out the away from the mother every time it divided and then count how many times the mother cells divides," said Dr. Kennedy. "We had several microscopes running all the time."

These efforts produced a wealth of information about how different genes, and their associated pathways, modulate aging in yeast. Deleting a gene called LOS1 produced particularly stunning results. LOS1 helps relocate transfer RNA (tRNA), which bring amino acids to ribosomes to build proteins. LOS1 is influenced by mTOR, a genetic master switch long associated with caloric restriction and increased lifespan. In turn, LOS1 influences Gcn4, a gene that helps govern DNA damage control.

"Calorie restriction has been known to extend lifespan for a long time." said Dr. Kennedy. "The DNA damage response is linked to aging as well. LOS1 may be connecting these different processes."

A number of the -extending genes the team identified are also found in C. elegans roundworms, indicating these mechanisms are conserved in higher organisms. In fact, many of the anti-aging pathways associated with yeast genes are maintained all the way to humans.

The research produced another positive result: exposing emerging scientists to advanced lab techniques, many for the first time.

"This project has been a great way to get new researchers into the field," said Dr. Kennedy. "We did a lot of the work by recruiting undergraduates, teaching them how to do experiments and how dedicated you have to be to get results. After a year of dissecting yeast cells, we move them into other projects."

Though quite extensive, this research is only part of a larger process to map the relationships between all the gene pathways that govern aging, illuminating this critical process in yeast, worms and mammals. The researchers hope that, ultimately, these efforts will produce new therapies.

"Almost half of the genes we found that affect aging are conserved in mammals," said Dr. Kennedy. "In theory, any of these factors could be therapeutic targets to extend healthspan. What we have to do now is figure out which ones are amenable to targeting."

Explore further: Cell aging slowed by putting brakes on noisy transcription

More information: A comprehensive analysis of replicative lifespan in 4,698 single-gene deletion strains uncovers novel mechanisms of aging, Cell Metabolism, 2015.

Related Stories

Cell aging slowed by putting brakes on noisy transcription

July 30, 2015

Working with yeast and worms, researchers found that incorrect gene expression is a hallmark of aged cells and that reducing such "noise" extends lifespan in these organisms. The team published their findings this month in ...

Slowing the ageing process—it's in your genes

September 5, 2013

Imagine being able to take a drug that can reduce the rate at which you age. Research by Massey University senior lecturer in genetics Dr Austen Ganley is making this dream one step closer to reality.

Turning off the 'aging genes'

January 2, 2014

Restricting calorie consumption is one of the few proven ways to combat aging. Though the underlying mechanism is unknown, calorie restriction has been shown to prolong lifespan in yeast, worms, flies, monkeys, and, in some ...

Penn yeast study identifies novel longevity pathway

May 8, 2014

Ancient philosophers looked to alchemy for clues to life everlasting. Today, researchers look to their yeast. These single-celled microbes have long served as model systems for the puzzle that is the aging process, and in ...

Recommended for you

These shrews have heads that shrink with the season

October 23, 2017

If any part of the body would seem ill equipped to shrink, it would probably be the head and skull. And, yet, researchers reporting in Current Biology on October 23 have found that the skulls of red-toothed shrews do shrink ...

Single-molecule dissection of developmental gene control

October 23, 2017

Scientists at EPFL and Max Plank have made significant discoveries on how developmental genes are controlled by the methyltransferase enzyme PRC2. The study is published in Nature Structural & Molecular Biology.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.