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

September 29, 2022

The genetic determinants of longevity: A fresh glance

An eagerly awaited, massively parallel mouse study on the genetics of longevity dropped results today, and as expected, they open new doors. Led by researchers from EPFL in Lausanne, Switzerland, and the University of Tennessee Health Science Center in Memphis, the study followed 3,276 mice from the National Institute on Aging’s Interventions Testing Program over the 800+ days of their lives. Researchers looked at sex- or age-specific genetic longevity effects, correlated that with distinct genes that influence body weight variation, and explored influences like litter size and early access to nutrients as a young pup. Drug hunters will applaud the experimentally validated longevity genes they identified—Hipk1DdostHspg2Fgd6, and Pdk1, which could help identify new pharmaceutical targets. Systems biologists will dig the cross-species, hypothesis-building online interactive resource they compiled for prioritizing longevity genes. We love the deepening mystery: Is longevity driven by small impacts from a large number of known genes, large impacts of a few as-yet-unknown genes, or the mysterious interaction of all those genes and the environment put together? Science

New LSD-like drugs with no psychedelic effects

As we have reported in the past, high interest in psychedelic medicine is revealing a growing divide in psychiatry. There are two distinct visions of the future: One of sober neurochemistry that seeks to develop LSD-like chemicals that render therapy without hallucination, and another of spiritual interconnectedness, where psychedelics are administered to full effect and tripping is seen as integral to healing. A new study published yesterday suggests the chemists could be winning. A team of researchers at UCSF, Yale, UNC, Duke, and Stanford universities built a structure-based drug-design library of 75 million virtual chemicals and searched for molecules that could bind to the serotonin 5-HT2A receptor (a key protein in the human brain that mediates hallucinations). They identified, synthesized, and optimized two molecules as potential lead compounds for new therapeutics. Tested in mice, both were potent antidepressants, with the same efficacy as Prozac at 1/40th the dose—but with no psychedelic activity. Nature

Strength training + aerobics for longer life

An analysis of questionnaires given to nearly 100,000 adults involved in a 30-year-old U.S. study known as the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial has found lower mortality risk for people who do twice-weekly muscle-strengthening activities like weight lifting or who achieve the recommended amount of aerobic exercise—about 150–300 minutes per week of moderate-intensity activity, 75–150 minutes per week of vigorous activity, or some combination thereof. According to researchers at the National Cancer Institute and the University of Utah, both types of exercise were associated with a lower risk of all-cause mortality and cardiovascular disease mortality, and “appeared to be lowest for those who participated in both types of exercise.” British Journal of Sports Medicine

Big win for the bionic pancreas

Doctors at Massachusetts General Hospital in Boston have completed a 13-week randomized clinical trial involving 219 adults and children with type 1 diabetes, two-thirds of whom tested a device known as a bionic pancreas. The trial compared how well the device can maintain blood sugar compared to the current generation of real-time continuous glucose monitoring systems. The advantage of the bionic pancreas is that it more fully automates treatment compared to existing “closed-loop system” devices on the market. Those devices monitor blood glucose and release insulin automatically, but they still take daily user input and attention, requiring people to hand-enter the estimated number of grams of carbohydrate at each meal and initiate needed doses of insulin at times. The bionic pancreas promises to be much easier, dispensing insulin on its own and demanding less user input. The trial showed that it was better at maintaining gold-standard medically recommended reduced levels of glycated hemoglobin—something only 20 percent of people with type 1 diabetes in the United States are typically able to achieve. NEJM

Non-genetic “epigenetic” inheritance seen in worms

Researchers at the University of California Santa Cruz have demonstrated how a type of non-genetic chemical change to a specific protein involved in packaging the DNA of C. elegans worms can be passed along from a parent to its offspring and later inherited by the next generation as well. An example of “transgenerational epigenetic inheritance,” the work involves a specific epigenetic modification known as H3K27me3, which alters a protein in the nucleus of worm cells. The demonstration that this change can be passed on and inherited by multiple generations is relevant to human health because there may be similar mechanisms at play in people, allowing your health and development to be impacted by experiences your parents or grandparents had years ago. PNAS

New biochemical aging clock highlights impact of psychology

Using data collected from 4,451 healthy adults enrolled in the China Health and Retirement Longitudinal Study, researchers at the Hong Kong-based biotech company Deep Longevity Limited have developed a new type of “clock” for measuring biological age. Based on a deep learning AI trained on a set of 16 blood biomarkers, the clock highlights the importance of your psychological condition in your rate of aging. It predicts some psychological factors, like depression or loneliness, may contribute significantly to your age—work which highlights the need for “a psychologically pleasant environment for healthy longevity,” the researchers write. Aging