News | Spanish Study Warns That Mixed Mitochondrial DNA May Affect Health and Longevity
A study by Spain's Centro Nacional de Investigaciones Cardiovasculares (CNIC) has identified potentially serious long-term health effects when mitochondrial DNA (mtDNA) from different sources is mixed. Published in Circulation, the findings provide important scientific evidence and a safety warning for mitochondrial interventions.
Concerns Behind "Three-Parent Baby" Technology
Mitochondrial DNA is maternally inherited genetic material found in cellular mitochondria and consists of 37 genes. In recent years, advanced reproductive technologies such as Mitochondrial Replacement Therapy (MRT) and cytoplasmic injection have been used to prevent the transmission of maternally inherited diseases or to treat infertility. These techniques generally involve introducing donor mitochondria into a patient's egg, creating what is commonly called a "three-parent baby."
Study leader Dr. José Antonio Enríquez, head of the Genetics of the Oxidative Phosphorylation System (GENOXPHOS) group, said, "This technology initially appeared successful in animal models, with healthy young individuals. Long-term observation, however, found serious problems in adulthood, including heart failure, pulmonary hypertension, muscle loss, frailty, and even premature death."
Metabolic Harm from Mixing Different Sources of Mitochondrial DNA
Under normal conditions, mtDNA in cells usually comes from a single source, a state called homoplasmy. Mixed mtDNA, called heteroplasmy, is very rare, is often caused by mutations, and can lead to various diseases.
In this study, researchers introduced two completely normal but differently sourced types of mtDNA into mice for the first time. Long-term monitoring showed that:
Most tissues gradually eliminated one mtDNA type to maintain homoplasmy;
However, key organs such as the heart, lungs, and skeletal muscles could not effectively remove the foreign mtDNA, causing ongoing mitochondrial dysfunction;
These tissues could not adapt to mixed mtDNA, resulting in metabolic deterioration, accelerated tissue aging, and higher mortality.
The mice showed no obvious symptoms when young, but their mitochondrial metabolism declined over time and they developed clear organ damage, confirming the potential long-term toxicity of mixed mtDNA.
Why Is Mitochondrial DNA Inherited Only from the Mother? Science Finds Part of the Answer
Lead author Dr. Ana Victoria Lechuga-Vieco said, "It remains unclear why mtDNA is inherited only through the maternal line, but this study shows for the first time that breaking this natural barrier and mixing mtDNA poses a substantial health risk."
The study also found that cells "select" between two mtDNA versions, a process influenced by cellular metabolic state, gene function, medication, and dietary changes. This means that even an apparently healthy combination of mtDNA may be incompatible because of differences in metabolic regulation.
Implications and Recommendations for Mitochondrial Treatments
Despite identifying new biological risks, Dr. Enríquez does not believe mitochondrial replacement therapy should be abandoned. He emphasized, "Just as blood type and tissue matching are required for transfusions or organ transplants, mitochondrial treatments must also ensure a high degree of mtDNA compatibility between donor and recipient."
The study also noted:
Even when replacing abnormal mitochondria, 100% replacement may not be achieved because recipient cells may preferentially retain their original mtDNA;
Cytoplasmic injection carries similar risks and may also result in mixed mtDNA;
Mitochondrial injection therapies for cardiopulmonary or neurological conditions should also account for these potential adverse effects.
Future interventions involving mtDNA must therefore fully consider genetic compatibility, tissue selectivity, and long-term safety in their design.
Study Background and Publication
The study was led by the GENOXPHOS group at Spain's Centro Nacional de Investigaciones Cardiovasculares. The paper, titled "Wild-Type Mitochondrial DNA Heteroplasmy Results in Metabolic Heart Disease, Pulmonary Hypertension, and Frailty," was published in Circulation in 2022.
News | Spanish Study Warns That Mixed Mitochondrial DNA May Affect Health and Longevity
News | Spanish Study Warns That Mixed Mitochondrial DNA May Affect Health and Longevity
A study by Spain's Centro Nacional de Investigaciones Cardiovasculares (CNIC) has identified potentially serious long-term health effects when mitochondrial DNA (mtDNA) from different sources is mixed. Published in Circulation, the findings provide important scientific evidence and a safety warning for mitochondrial interventions.
Concerns Behind "Three-Parent Baby" Technology
Mitochondrial DNA is maternally inherited genetic material found in cellular mitochondria and consists of 37 genes. In recent years, advanced reproductive technologies such as Mitochondrial Replacement Therapy (MRT) and cytoplasmic injection have been used to prevent the transmission of maternally inherited diseases or to treat infertility. These techniques generally involve introducing donor mitochondria into a patient's egg, creating what is commonly called a "three-parent baby."
Study leader Dr. José Antonio Enríquez, head of the Genetics of the Oxidative Phosphorylation System (GENOXPHOS) group, said, "This technology initially appeared successful in animal models, with healthy young individuals. Long-term observation, however, found serious problems in adulthood, including heart failure, pulmonary hypertension, muscle loss, frailty, and even premature death."
Metabolic Harm from Mixing Different Sources of Mitochondrial DNA
Under normal conditions, mtDNA in cells usually comes from a single source, a state called homoplasmy. Mixed mtDNA, called heteroplasmy, is very rare, is often caused by mutations, and can lead to various diseases.
In this study, researchers introduced two completely normal but differently sourced types of mtDNA into mice for the first time. Long-term monitoring showed that:
Most tissues gradually eliminated one mtDNA type to maintain homoplasmy;
However, key organs such as the heart, lungs, and skeletal muscles could not effectively remove the foreign mtDNA, causing ongoing mitochondrial dysfunction;
These tissues could not adapt to mixed mtDNA, resulting in metabolic deterioration, accelerated tissue aging, and higher mortality.
The mice showed no obvious symptoms when young, but their mitochondrial metabolism declined over time and they developed clear organ damage, confirming the potential long-term toxicity of mixed mtDNA.
Why Is Mitochondrial DNA Inherited Only from the Mother? Science Finds Part of the Answer
Lead author Dr. Ana Victoria Lechuga-Vieco said, "It remains unclear why mtDNA is inherited only through the maternal line, but this study shows for the first time that breaking this natural barrier and mixing mtDNA poses a substantial health risk."
The study also found that cells "select" between two mtDNA versions, a process influenced by cellular metabolic state, gene function, medication, and dietary changes. This means that even an apparently healthy combination of mtDNA may be incompatible because of differences in metabolic regulation.
Implications and Recommendations for Mitochondrial Treatments
Despite identifying new biological risks, Dr. Enríquez does not believe mitochondrial replacement therapy should be abandoned. He emphasized, "Just as blood type and tissue matching are required for transfusions or organ transplants, mitochondrial treatments must also ensure a high degree of mtDNA compatibility between donor and recipient."
The study also noted:
Even when replacing abnormal mitochondria, 100% replacement may not be achieved because recipient cells may preferentially retain their original mtDNA;
Cytoplasmic injection carries similar risks and may also result in mixed mtDNA;
Mitochondrial injection therapies for cardiopulmonary or neurological conditions should also account for these potential adverse effects.
Future interventions involving mtDNA must therefore fully consider genetic compatibility, tissue selectivity, and long-term safety in their design.
Study Background and Publication
The study was led by the GENOXPHOS group at Spain's Centro Nacional de Investigaciones Cardiovasculares. The paper, titled "Wild-Type Mitochondrial DNA Heteroplasmy Results in Metabolic Heart Disease, Pulmonary Hypertension, and Frailty," was published in Circulation in 2022.
Source:
Compiled from online sources