Can We Build a Longevity Therapy Atop Mitoptosis?
As you might have noticed, PubMed entries for papers in the next issue of Rejuvenation Research have been showing up of late. One of those papers looks at the prospects for harnessing mitoptosis as a longevity intervention, a topic guaranteed to catch my attention. What is mitoptosis? You can find a discussion thread on the topic with references over at the Immortality Institute. In essence, keeping it short, mitoptosis is the programmed destruction of mitochondria in your cells, a process analogous to apoptosis, or programmed cell death.
Mitoptosis: different pathways for mitochondrial execution
Mitoptosis was described as a sort of mitochondrial death program. It could be associated with both necrosis and apoptosis, although degenerating mitochondria are also found in autophagic vacuoles. It was demonstrated that several molecules might contribute to the remodeling and rearrangement of mitochondrial membranes, leading to mitochondria rupture and disruption. Here, we hypothesize that, at least in T cells, two main pathways of mitoptosis can occur: an inner membrane mitoptosis (IMM), in which only the internal matrix and cristae are lost while the external mitochondrial envelope remains unaltered, and an outer membrane mitoptosis (OMM) where only swollen internal cristae are detected as remnants.
But back to the Rejuvenation Research paper:
There is an imperative need for exploring and implementing mitochondria-rejuvenative interventions that can bridge the current gap toward the step-by step realization of strategies for engineered negligible senescence (SENS) agenda. Recently discovered in mammals, natural mechanism mitoptosis - a selective "suicide" of mutated mitochondria - can facilitate continuous purification of mitochondrial pool in an organism from the most reactive oxygen species (ROS)-producing mitochondria.Mitoptosis, which is considered to be the first stage of ROS-induced apoptosis, underlies follicular atresia (a "quality control" mechanism in female germline cells that eliminates most germinal follicles in female embryos). Mitoptosis can be also activated in adult postmitotic somatic cells by evolutionary conserved phenotypic adaptations to intermittent oxygen restriction (IOR) and synergistically acting intermittent caloric restriction (ICR).
IOR and ICR are common in mammals and seem to underlie extraordinary longevity and augmented cancer resistance in bowhead whales (Balena mysticetus) and naked mole rats (Heterocephalus glaber). Furthermore, in mammals IOR can facilitate continuous stromal stem cells-dependent tissue repair. A comparative analysis of IOR and ICR mechanisms in both mammals, in conjunction with the experience of decades of biomedical and clinical research on emerging preventative, therapeutic, and rehabilitative modality - the intermittent hypoxic training/therapy (IHT) - indicates that the notable clinical efficiency of IHT is based on the universal adaptational mechanisms that are common in mammals. Further exploration of natural mitochondria-preserving and -rejuvenating strategies can help refinement of IOR- and ICR-based synergistic protocols, having value in clinical human rejuvenation.
To understand why this is interesting, you'll want to wander back in the Fight Aging! archives and read up on the mitochondrial free radical theory of aging. To cut a long story short, damaged mitochondria in a cell will breed more damaged mitochondria in that cell. Repeated over and over, this eventually causes a small but significant number of cells to export damaging free radicals throughout your body, causing great harm to health and life span over time. One focus of SENS and SENS-like research is to cut this process short at the "damaged mitochondria" phase. Eliminate the damaged mitochondria aggressively and often, and that portion of the aging process is gone.
Mitoptosis may be an existing mechanism that can be adapted to this end - though whether this is the case, and whether it is at the root of some exception longevity in the animal kingdom, remains to accumulate greater weight of evidence. For example, much of the recent published work on naked mole-rat biochemistry has suggested that crucial cellular components are more resistant to oxidative damage than those in other rodents, being built of a different mix of biochemicals, rather than being more aggressively recycled and repaired.
The greater the number of potential avenues of approach to each aspect of SENS, each facet of a true therapeutic approach to rejuvenation and the repair of aging, the better off we are. Competition drives the wheel of progress, and choice of approach is a sign of real progress in science. So I am always pleased to see new additions to the stable of potential future medical technologies.