The week’s most astounding developments from the neobiological frontier.

March 10, 2022

The hibernation-aging hypothesis of longevity

The yellow-bellied marmot sounds like a spineless rodent only its mammalian mother would love, but the longevity community may soon embrace this aggressive, fat little ground squirrel for what it’s teaching us about metabolism. Species that hibernate are known to live longer than expected based on their body size, and a team of researchers at University of California, Los Angeles has proposed that this is due to the suspension of biological aging mechanisms as the animals cycle between long periods of metabolic suppression and short periods of bursting metabolism during their winter slumbers. The UCLA researchers call this the “hibernation–aging hypothesis,” and to demonstrate it, they collected blood samples of 73 female yellow-bellied marmots of different ages that were living freely in Gunnison National Forest, Colorado, and they measured their epigenetic ages with a Horvath clock. (The team was led by Steve Horvath, who pioneered the use of epigenetic markers to measure aging.) Understanding the biological connections between hibernation and longevity has huge implications for humans because it could point to ways to slow metabolism for long-haul, deep-space travel—or simply help people live longer here on Earth. Nature Ecology & Evolution

Immaculate conception achieved in mice

Despite what atheists may think of virgin births, the spontaneous development of an embryo from an unfertilized egg (technically known as “parthenogenesis”) is a common form of asexual reproduction seen in nature—in everything from worms, wasps, sharks, scorpions, and Komodo dragons—though never in mammals. Artificial mammalian parthenogenesis has been achieved in the lab, but with limited success because of something known as genomic imprinting, an epigenetic process in early development where the genes from one parent or the other are turned off. But when you inherit all your genes from your mother, that can cause genetic disease. Now a team of researchers at Shanghai Jiao Tong University in China found a way to rewire the process, allowing them to create 192 fatherless mouse embryos, resulting in 14 successful pregnancies and three live births. Only one pup survived to adulthood, but it wound up giving birth to its own litter, which the researchers say, “opens many opportunities in agriculture, research, and medicine.” PNAS

An “parthenogenetic” mouse born to a mother and no father, as an adult with pups of her own. Courtesy Yanchang Wei.

A protein atlas for human cells

Researchers at the Chan Zuckerberg Biohub in San Francisco announced today they have created a new research tool to help uncover how the ~20,000 proteins coded in the human genome are expressed and arranged in space and time within human cells—one of the major challenges of the post-genomic era as we seek to understand how human health and disease manifest at the micro- and nano-scale. Using CRISPR to manipulate the genomes of 1,310 different human cell lines, they engineered 1,310 different fluorescently tagged proteins into those cells and then they systematically analyzed their whereabouts and their interactions with other proteins using live-cell microscopy and mass spectrometry. Calling their basic research tool “OpenCell,” it has an associated, interactive website with tons of available data (and images), which is searchable for whatever cell type, protein, or interaction of interest. Check it out—it’s cool. Science

Long-term use of Yamanaka factors for aging

In 2006, Shinya Yamanaka showed that exposing an already differentiated, mature cell to four transcription factors (OCT4, SOX2, MYC, and KLF4) could convert it into a “pluripotent” embryonic state, for which he won the Nobel prize. Building on that idea, other researchers showed in recent years that these factors could reverse the effects of aging and extend lifespans when given to prematurely aging mice for short periods of time. Now researchers at Genentech in South San Francisco and Altos Labs in San Diego have tested long-term regimens of Yamanaka factors in normal, wild-type mice. They found the treatments to be safe and effective at preventing age-related physiological changes—though they didn’t test whether it actually helped the animals live longer. Nature Aging

Mice hold key to understanding why people make irrational choices

Why do consumers ignore good data and make inconsistent, biased, or otherwise irrational decisions against their own best interests? One popular explanation in economics is called “rational inattention theory,” which holds that humans are often awash in too much information and unable to process it all. When presented with a decision, they simplify their choice by limiting the information they take into account. Even though it has profound implications for everything from investment portfolios to political populism to central bank rate policies, our understanding of rational inattention theory is limited because it’s mainly been studied in people. There are no animal models of it, which would allow researchers to explore the influence of genes or probe the brain with neuronal implants. Now that may be possible. Researchers at ETH Zurich have developed a mouse model of rational inattention based on a split screen, ever-so-slightly different patterns, a wheel for the mouse to turn and choose a side, and a little sip of strawberry milkshake if they make the right choice. Oh if only real-world decision making were so simple—and its rewards as sweet! Science Advances