Lifelong mating made old female killifish livers look younger

Diet and exercise are well-known influences on how the body ages. Sexual reproduction is a much less studied one, especially in animals with a backbone. In worms and fruit flies, mating can shorten life. A team led from Stanford University asked what lifelong mating does to the organs of a vertebrate, and found that in old female fish it seemed to slow some signs of liver aging.

The animal is the African turquoise killifish, a small fish that lives only four to six months, which makes it possible to study a whole lifetime in a few months. Its eggs are fertilised and develop outside the body, with no pregnancy and no parental care. That lets researchers look at mating itself, separately from pregnancy and raising young, which can't be separated in mice.

The study is a preprint, not yet peer-reviewed.

What they did

• Two groups of fish. From sexual maturity until death, pairs of one male and one female were put together for four-hour mating sessions twice a week. Fish of the same age in the control group went through exactly the same handling, but never met a partner.
• Looking at the liver. The team chose the liver because it is closely tied to reproduction in vertebrates. In young (about 2 months) and old (about 4.5 months) fish, they measured which genes were active in single liver cells, counted immune cells under the microscope and measured fats.
• A stress test. Old females were exposed to an overdose of acetaminophen (paracetamol), a common cause of liver failure in people, to see how well their livers coped.
• Other organs. They also measured gene activity in the brain, gut and kidney.
• A look at people. Using blood-protein data from the UK Biobank, they estimated the "biological age" of different cell types in women who had never given birth and compared those who had had sex with 165 women who reported never having had sex.

What they found

• Younger-looking liver cells, in females only. A computer model trained to tell young from old cells rated a larger share of liver cells from old mated females as "young" than from old unmated females. Most of the gene changes that came with age in unmated females went in the opposite direction in mated ones. In males, no clear effect was seen.
• Less inflammation. Old mated females had fewer immune cells in the liver, including macrophages and neutrophils, and lower levels of an inflammation marker in ordinary liver cells.
• Less fat in the liver. Several classes of lipids (fats and fat-like molecules) were lower in the livers of old mated fish, in both sexes.
• Coping with poison. After the acetaminophen overdose, old mated females survived better in all three groups of fish tested, but the overall difference just missed the usual threshold for being statistically significant.
• Eggs may matter. In females with a gene change that made their eggs infertile, mating no longer lowered liver immune cells. This hints that something linked to egg maturation, rather than simply contact with a male, drives the effect.
• Other organs. Gene activity linked to inflammation was lower in the brain and gut of old mated fish of both sexes.
• In women, those who had had sex (without pregnancy or birth) had a younger estimated age for liver cells and several other cell types. This difference wasn't explained by overall health, smoking, drinking or loneliness.

What to keep in mind

• Fish are not people. Killifish reproduce very differently from humans, most obviously without pregnancy. The study didn't measure whether mating changed how long the fish lived.
• Small groups. Most measurements used 4 to 7 fish per group. The survival benefit in the poison test was consistent but not statistically significant.
• Mostly gene activity. Much of the "younger" signal comes from gene activity patterns, which are a sign of aging but not the same as a healthier organ. The fat and survival results are the more direct functional tests.
• The human analysis is a snapshot. It compares 165 women with a much larger group and, as the authors say, cannot show which way the relationship runs. They also note that factors such as contraceptives, medications and income may play a part.
• Not yet peer-reviewed.

Why it matters

Mating status is rarely recorded in laboratory studies of aging, and this study suggests it may matter, at least in fish. It also cuts against a common expectation: in worms, flies and female mice, mating has been linked to shorter lives, but here it seemed to ease some signs of liver aging in females. The authors suggest that mating may have both good and bad effects on different organs. The human data is only a first hint, and nothing in the study tells anyone how to live.