What the young can give to the old

Paul Bert, a pioneering 19th-century French physiologist, added a gruesome new procedure to laboratory experimentation: grafting mice together rather as a gardener grafts branches onto a tree. Part of the idea was to discover what qualities could be passed from one mouse to the other through the blood they now shared. In the 1950s such “parabiosis” experiments led to the suggestion that one such thing was youth. Older rats, after several weeks grafted to younger rats, showed signs of rejuvenation.

The experiments were widely ignored until new interest in the science of ageing brought them to light in the 2000s. Since then the phenomenon has attracted new interest among both scientists and a number of people who might charitably be described as chancers. Young-to-old transfusions of human blood plasma allow wealthy clients to take a punt on the blood of hard-up students.

There may be substances in young blood that help the old, such as taurine or humanin. However it seems quite likely that the effect seen in older rats owes more to the removal of detritus than an influx of the essence of youth. In 2020 Irina Conboy of the University of California, Berkeley, and her colleagues found that replacing half of an old mouse’s blood with just albumin, a blood protein, and saline solution had the same rejuvenating effect as young-mouse blood. Old blood may need filtering and dilution, not supplementing.

Intriguingly, blood is not the only thing which, if transfused between old and young animals, has an effect on how they age. Gut microbes do so, too. A body’s microbial inhabitants are not mere hangers-on; evolution has built them a role in their host’s well-being. Gut bacteria liberate inaccessible nutrients from food and synthesise molecules their host cannot.

Some of the parabiosis experiments in the 1950s were aimed at discovering whether the microbiome of the old mouse would be rejuvenated by young blood. (It was not.) But taking poo (and the microbes it contains) out of the digestive tract of a young mouse and putting it into the gut of an older one seems to enhance both lifespan and healthspan in “progeric” mice engineered for early ageing.

A study of 9,000 individuals aged between 18 and 101 by a team of investigators at the Institute for Systems Biology, in Seattle, revealed three things about the ageing microbiomes in their guts.

First, in middle age people’s microbiomes become increasingly dissimilar from individual to individual. Second, this process of increasing distinctiveness continues in healthy people as they get older but stops in those who are unhealthy. Third, in those aged 85 or more, lack of such distinctiveness is a harbinger of earlier death.

There are broad hints as to which microbes are the ones that matter. Lactobacillus plantarum both extends lifespan and alleviates cognitive decline in progeric mice. Its presence is also, intriguingly, boosted by calorie-restricted diets. Conversely, retention into old age of lots of bacteria of the genus Bacteroides is a known predictor of mortality. But the key message of the institute’s studies is that an old-age-friendly microbiome is one well adjusted to its unique circumstances. More fundamental insights into how the microbiome adapts to its host, and vice versa, may be necessary before a road to an enduring old age through the gut can be established.■