News in brief
Authors: Jack Williamson
Journal: The Lancet Healthy Longevity (2021)

Beyond the age of 50 years, 15–20% of human muscle mass is lost each decade. Sarcopenia, an age-related skeletal-muscle wasting syndrome, is associated with a large health-care burden and currently has no approved therapy. In a study using muscle samples from aged mice, Helen Blau (Stanford School of Medicine, Stanford, CA, USA) and colleagues investigated the role of 15-PGDH, the enzyme that degrades prostaglandin E2 (PGE2), in muscle atrophy and strength. Overexpression of 15-PGDH was shown to be a hallmark of aged muscles in both mice and human samples, as well as for aged heart, skin, colon, and skin tissues. Moreover, in aged mice, inhibition of 15-PGDH (via either genetic knockdown or small molecule inhibition) countered muscle atrophy and significantly increased muscle mass, strength, and endurance after a month. These results implicate 15-PGDH as a marker of aged muscles in both mice and humans, and as a potential therapeutic target for sarcopenia-associated muscle deterioration. “I can't remember winning the world cup”, said Steve Thompson, the 2003 English Rugby World Cup champion, aged 42 years. The statement was made after being diagnosed with early-onset dementia, with probable chronic traumatic encephalopathy, as a result of repeated collisions to the head that top players of the sport are required to undergo. Thompson and eight other former players have brought legal proceedings against World Rugby—the sport's governing body—and the English and Welsh rugby unions, for their failure to protect players from brain damage caused by repeated concussions. As well as seeking personal compensation for medical injuries associated with dementia, costs of care, and diminished future employment prospects, the former players are calling for 15 key changes to the game. These suggestions include reduced contact in training, fewer tactical substitutions, and compulsory brain tests for players who have had concussions, and draw from beneficial changes made to the American National Football League (NFL) after the successful 2012 appeal to compensate similarly injured players. The human cost of head-collision sports, such as rugby, must be recognised. As the example of the NFL has shown, injuries can be substantially reduced without reducing the game itself. Cardiovascular diseases (CVDs) account for approximately 18 million deaths worldwide per year, 80% of which occur in low-income and middle-income countries. In The International Polycap Study-3 (TIPS-3), the largest randomised controlled trial of a quadruple fixed-dose drug combination (known as a polypill) for CVD up to now, Salim Yusuf (McMaster University, Hamilton, ON, Canada) and Prem Pais (St John's Research Institute, Bangalore, India) and colleagues analysed four common cardiovascular medications that, if proven safe and effective, could be mass produced for as little as US$0·10 per dose per day. Comparing 5713 participants without CVD who were randomly assigned to either the polypill (containing a statin and three blood-pressure lowering drugs), aspirin, both the polypill and aspirin, or double placebo, the study showed that the polypill plus aspirin combination led to a 31% lower relative risk of cardiovascular events after 4·6 years than in the placebo group. For primary prevention in people without CVD but who have at least one risk factor for CVD (eg, elevated cholesterol), the polypill with aspirin combination could represent a cost-effective and simple treatment to save millions of lives worldwide. Changes over time in DNA methylation patterns that affect gene expression, known as epigenetic patterns, is a putative mechanism of ageing. The unidirectionality of these changes is now being called into question. Is it possible, for instance, that underneath this epigenetic noise there remains a faithful copy of the youthful epigenetic signature? If so, would restoration of this signature reverse phenotypic ageing? These questions were asked by Yuancheng Lu (Harvard Medical School, Boston, MA, USA) and colleagues who, using murine retinal ganglion cells, restored youthful DNA methylation patterns by ectopically expressing three of the so-called Yamanaka factor genes (Oct4, Sox2, and Klf4 [OSK]). In addition, OSK-induced reprogramming promoted axon regeneration after injury in an optic-nerve crush injury model, and reversed vision loss in aged mice and in a mouse glaucoma model, providing in vivo evidence that OSK reprogramming could help recover vision loss and improve tissue function and regeneration. Although overinterpretation of in vivo results to human trials must be avoided, these important findings provide new insights into the mechanisms of ageing and novel possible therapies for age-related degenerative conditions. For Lu and colleagues' study see Nature 2020; 588: 124–29For more on Yamanaka factor genes see Nature 2020; 588: 34–36 For Lu and colleagues' study see Nature 2020; 588: 124–29 For more on Yamanaka factor genes see Nature 2020; 588: 34–36