While individuals universally desire a lengthy existence, the utmost coveted aspect is an extended period of vitality and good health, known as “healthspan,” which precedes the inevitable deterioration that accompanies older age. Scholars at UC Santa Barbara have uncovered that the cellular mechanisms responsible for inducing cell death in times of distress actually contribute to a prolonged and healthier life by revitalizing specialized cellular compartments called mitochondria.
Mitochondria are responsible for generating the energy required for all bodily functions, from basic movements to cognitive processes. These energy-producing powerhouses, housed within our cells, originated from ancient free-living bacteria.
Joel Rothman, a professor of molecular biology who conducted the research, highlights the dual evolutionary origin of our cells. He notes that humans are a unique hybrid creature resulting from the fusion of two independent evolutionary lineages: mitochondria, which were once bacteria, and the surrounding cellular environment.
Consequently, our DNA is located in two distinct compartments within each cell: the nucleus, where most of our genetic material is situated, and the mitochondria, which retain their own DNA as a vestige of their bacterial ancestry.
Rothman explains that as we age, DNA damage accumulates within these cellular powerhouses, contributing to age-related decline. The team’s discovery unveils a mechanism through which defective mitochondria are eliminated, leading to cell rejuvenation.
The research, recently published in the journal eLife, brings to light that the biological machinery responsible for triggering cellular death in potentially harmful cells, such as cancerous ones, is also involved in removing defective mitochondrial DNA.
Pradeep Joshi, a senior scientist and co-author of the publication, describes mitochondria as having both positive and negative aspects. While these powerhouses produce the energy necessary for sustaining life, they also generate reactive oxygen species, harmful molecules that inflict damage upon DNA and other cellular components.
Consequently, the longer we live, the more extensive the damage becomes. This damage impairs energy production by mitochondria, resulting in adverse effects on our healthspan. As the heart, muscles, and brain have the highest energy requirements, aging inevitably brings heart failure, loss of muscle function, and cognitive impairment.
Joshi suggests that aging can be perceived as a form of mitochondrial disease. If mitochondrial damage could be cleared, an improvement in healthspan and longevity could be achieved.
To investigate the removal of damaged mitochondria, the research team utilized a tiny worm called C. elegans, renowned for its contributions to biomedical advances and the recipient of six Nobel prizes.
The team discovered that the enzymes responsible for cell death are also crucial for eliminating damaged mitochondrial DNA. Without these enzymes, defective mitochondria accumulate.
Surprisingly, Rothman and his colleagues found that although some proteins play similar roles, the overall mechanism for eliminating damaged mitochondria differs from the process involved in removing surplus cells. Joshi observes that the machinery responsible for cell death appears to have adapted to eliminate dysfunctional mitochondria, thus restoring vitality to these essential powerhouses.
In humans, mitochondrial DNA is solely inherited from the mother, a pattern also observed in the animals used in this study. The researchers determined that the burden of defective mitochondria in mothers increases with age, and unfortunately, these faulty mitochondria are passed down to their offspring.
However, there is encouraging news. The team discovered that a single genetic alteration, which slows down the aging process and extends lifespan, reduces the accumulation and inheritance of defective mitochondria.
Rothman, who is also the founding Director of the Center for Aging and Longevity at UCSB, notes that slowing down the “aging clock” leads to a gradual build-up of defective mitochondria. This raises the possibility that anti-aging interventions could result in healthier mitochondria.
These remarkable findings open up avenues for future strategies to eliminate impaired mitochondria and rejuvenate cells. Ultimately, these advancements pave the way for additional years of vibrant, disease-free life for all individuals to enjoy.