Will Rejuvenation Therapies Be Useful for Progeria Patients?
Progeroid conditions are colloquially described as accelerated aging, but they are not in fact accelerated aging. They are only tangentially related to normal aging, in the sense that they are a form of molecular damage run rampant, and such damage tends to produce tissue and organ dysfunction that broadly resembles aging. It is not the same, however. Some progerias arguably involve forms of damage that do exist in normal aging and do contribute to normal aging, but when that damage represents near 100% of the total damage burden, rather than the normal much lesser fraction, the outcome ceases to be something that we can legitimately call aging. We cannot use it to teach us much about normal aging, and most of the rejuvenation treatments that will be beneficial to normally aged individuals will likely do little for a progeria patient. Only where the form of damage in a progeria aligns with a specific approach to rejuvenation through damage repair might there be utility.
All of the so-called "premature aging" diseases are in one critical sense entirely different from aging, inasmuch as they are the result of a relatively simple, unitary problem: patients carry just one key mutation in their cells. By contrast, real aging is the result of many different kinds of damage - and that damage accumulates as an unintended result of normal, healthy genes carrying out normal, life-sustaining metabolic processes that unfortunately inflict damage on previously healthy, non-mutated cells. In aging, there is no underlying mutation to fix, and we interfere with normal metabolic processes at our peril. So repairing the many different kinds of cellular and molecular aging damage is our best path to a future where we can live free of age-related ill-health.
"Damage-repair" rejuvenation biotechnologies might very well help progeria patients by removing, repairing, or replacing the subset of their cellular abnormalities that occur in their bodies and line up closely enough with forms of cellular and molecular aging damage targeted by these SENS-like damage-repair approaches. For instance, the high burden of what appear to be senescent cells in Hutchinson-Gilford Progeria Syndrome (HGPS) patients and mouse models is the result of a mutation in the gene for LMNA, whose encoded proteins are important structural components of the nuclear envelope, leading to senescent-cell-like phenotypes. The accumulation of senescent cells is, of course, involved in normal aging.
Even if the abnormal cells accumulating in HGPS patients' bodies aren't true senescent cells, there's still every reason to expect these patients to benefit from destroying the aberrant cells. This isn't just a reasonable prediction from first principles: it has proof-of-concept. In an animal study, scientists destroyed large numbers of the senescent-like cells in the tissues of mice with the same mutation as HGPS patients engineered into their genome. However, even after this senolytic treatment, however, these mice still aren't nearly as healthy or as long-lived as normal mice. HGPS causes other abnormalities in non-"senescent" cells, and both these mice and HGPS patients are rapidly accumulating these abnormal cells in comparison to normal individuals.
Link: https://www.sens.org/will-sens-benefit-progeria-patients/