‘You can blame your mother for how you age’

• Donor mitochondria could influence metabolism, ageing
• Mouse study has implications for three-parent babies
• IVF doesn’t up long-term breast cancer risk, study finds

Are mothers to be blamed for how we age?

A new research has shown that for a ‘three-parent baby,’ getting disease-free mitochondrial Deoxyribonucleic Acid (DNA)/genetic material from a surrogate may do more than just avert disease.

Mitochondria are the energy factories of the cells, in which the biochemical processes of respiration and energy production occur.

DNA is a molecule that carries the genetic instructions used in the growth, development, functioning and reproduction of all known living organisms and many viruses.

Surrogate is a woman who gets artificially inseminated with the father’s sperm. She then carries the baby and delivers it for another woman and her partner to raise.

The researchers reported online July 6 in Nature that for better or for worse, a donor’s mitochondria could also affect the course of ageing and that two strains of mice – genetically identical except for the source of their mitochondria, the energy centers of cells – aged very differently.

They found that even though both mouse strains had healthy mitochondrial DNA, the mice with mitochondria that did not come from the same source as the rest of their DNA fared better later in life: After two years, these mice showed fewer signs of ageing and had a lower incidence of tumors.

The researchers cautioned that the results don’t necessarily mean that mitochondria transplant leads to a healthier life, that this is just one case. Other DNA mixes and matches could turn out differently. But the study’s finding does point to a larger relationship between mitochondrial DNA and aging and raises new questions about the long-term effects of creating three-parent babies.

Also, a long-term study has shown that women who underwent in vitro fertilization (IVF) are not significantly more likely to develop breast cancer than women in the general public or women who opted for other fertility treatments.

The results are reported July 19 in JAMA.

The fertility treatment alters progesterone and estradiol levels in women trying to get pregnant. Yo-yoing hormones have been linked to an increase in a woman’s odds of developing breast cancer, but studies are divided on whether IVF itself actually ups cancer risk.

A neurologist at Columbia University, United States (U.S.), Michio Hirano, who was not involved in the study, said: “What the new results mean for people is still unclear, but if the findings do apply to humans. You can blame your mother for how you age.”

Mitochondrial DNA is passed down from mother to child. Three-parent babies are created through an in-vitro fertilization (IVF) technique that substitutes a mother’s diseased mitochondria for the healthy mitochondria of a surrogate. In the procedure, which is legal in the United Kingdom and deemed ethical by a U.S. panel of experts this year, a baby inherits its nuclear DNA- the majority of its genetic fingerprint- from mom and dad. But a small amount of DNA, just 37 genes, comes from the mitochondria of a second, healthy woman.

Mitochondria do more than just power cells; they also play big roles in cell-to-cell communication and metabolism. Over the last two decades, mitochondria have also been implicated in aging but without conclusive evidence. The new research fuels to this debate.

Mitochondrial donation (sometimes called mitochondrial manipulation technology or MMT) is a special form of IVF in which the future baby’s mitochondrial DNA comes from a third party. This technique is used in cases when mothers carry genetic mitochondrial diseases, and conventional in vitro fertilization techniques do not work. Mitochondrial diseases often involve energy production issues, and ultimately muscular issues down the road for people affected.

The two most common techniques in mitochondrial donation are pronuclear transfer and maternal spindle transfer. What this implies is that a baby is being produced with the DNA of both parents, as well as some DNA from a healthy donor of mitochondrial contents. Due to the uncharted nature of producing a child with three sources of DNA, this subject is currently quite contentious in the field of bioethics, as is the case with many other gene therapies.

Currently, mitochondrial donation techniques are legal in the United Kingdom (U.K.). In February 2016, a report was issued by the U.S. Food and Drug administration (F.D.A.) declaring that further research into mitochondrial donation is ethically permissible. There are many active debates on the matter, as of 2016.

Meanwhile, in the current study, José Enríquez of the Spanish National Center for Cardiovascular Research in Madrid and colleagues bred two strains of mice. The original strain was called C57/Black 6. A second strain of C57/Black 6 carried mitochondria from another kind of mouse called NZB. This mismatch mimicked the effects of a mitochondrial transplant. Early in life, normal C57 mice bulked up faster than those carrying NZB mitochondria and had 11 percent longer telomeres (protective caps at the ends of chromosomes that get shorter over time, so are used as a proxy for aging). But later in life, the mice with NZB mitochondria had longer telomeres, less fat in their muscles and lower risk of having liver tumors at the end of their lives.

Enríquez said: “Young C57 mice tend to be stronger, probably because their mitochondrial and nuclear DNA are a good match and make efficient mitochondria. The weaker batteries in the mice with mismatched mitochondria may cause more cellular stress early on, which may toughen up these mice to age more gracefully.”

Since the study was done in mice, researchers don’t know how mitochondrial substitution would affect ageing in humans. Enríquez urged caution, to avoid unforeseen and unwanted consequences.

He said: “Before we understand it better, a mitochondrial transplant should mimic natural conditions. Why don’t we match the mitochondrial DNA of the donor and receptor?”

Alexandra van den Belt-Dusebout of the Netherlands Cancer Institute in Amsterdam and her colleagues tracked 19,158 women who underwent in vitro fertilization treatment between 1983 and 1995 and 5,950 women who underwent other fertility treatments between 1980 and 1995.

Following up two decades later, the team found that 948 of the women had developed breast cancer. But breast cancer rates didn’t differ much between groups: 163.5 per 100,000 women for those who had IVF compared to 167.2 women on other fertility treatments and 163.3 women in the general public.