There is enthusiasm in the research community for in vivo cellular reprogramming as a path to treat aging. Reprogramming somatic cells to pluripotency recaptures some of the processes that take place in the developing embryo, and has been shown to restore youthful patterns of gene expression, leading to improved mitochondrial function.
Reprogramming can't do much for DNA damage or forms of persistent molecular waste in long-lived cells, but forms of reprogramming may be able to improve tissue function to a sizable enough degree to be worth the effort. Early results in mice are promising. There is a long way to go in order to produce systems of reprogramming that are safe enough and sophisticated enough to be used systemically, however, rather than in comparatively small and isolated areas of the body, such as the retina.
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As we age, we become increasingly vulnerable to age-related diseases. The progressive aging of the population makes this issue one of, if not the, major current scientific concern in the field of medicine. Aging is an intricate process that increases the likelihood of cancer, cardiovascular disorders, diabetes, atherosclerosis, neurodegeneration, and age-related macular degeneration. The regenerative capacity of cells and tissues diminishes over time and they thus become vulnerable to age-related malfunctions that can precipitate death.
Developing prophylactic strategies to increase the duration of healthy life and promote healthy aging is challenging, as the mechanisms causing aging are poorly understood, even if great progress has been made from studying naturally occurring or accelerated-aging phenomena. We now know that aging inculcates many changes, or 'hallmarks': genomic instability, telomere shortening, epigenetic alterations, loss of proteostasis, cellular senescence, mitochondrial dysfunction, deregulated nutrient sensing, altered intercellular communication, and stem cell compromise and exhaustion. These various hallmarks of aging are all active fields of molecular mechanistic study with much promise but relatively few tangible results have been translated into therapy.
Perhaps the most effective strategies so far have been those that focus on the removal of senescent cells with 'senolytic' drugs. In some ways, however, we feel this is too focused on the symptoms of aging whereas perhaps the most promising strategy for the future would be to focus on the causes of aging and its corollary, the rejuvenative capacity of stem cells.
Simply expressing four transcription factors, OCT4, SOX2, KLF4 and c-MYC (OSKM), converts somatic cells into induced pluripotent stem cells (iPSCs). Reprogramming occurs through a global remodeling of the epigenetic landscape that ultimately reverts the cell to a pluripotent embryonic-like state, with properties similar to embryonic stem cells (ESCs). This cellular reprogramming allows us to imagine cell therapies that restore organ and tissue function. Indeed, by reprogramming a somatic cell, from a donor into iPSCs, these cells can then be modified or corrected before redifferentiation, to produce 'rejuvenated' cells, tissues or organs, for replacement in the same donor or an immune-compatible person.
In recent years, emerging results have led to new ideas demonstrating that the mechanics of cellular reprogramming can be used to reduce the deleterious effects of aging and to delay these effects by increasing regenerative capacity, either at the cellular or the whole-organism level.
Link: https://doi.org/10.3390/ijms22083990
Source: Fight Aging!