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What It Will Be Like to Be an 85-Year-Old in the 2070s – Article by Scott Emptage

What It Will Be Like to Be an 85-Year-Old in the 2070s – Article by Scott Emptage

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Scott Emptage


I will be 85 sometime in the early 2070s. It seems like a mirage, an impossible thing, but the future eventually arrives regardless of whatever you or I might think about it. We all have a vision of what it is to be 85 today, informed by our interactions with elder family members, if nothing else. People at that age are greatly impacted by aging. They falter, their minds are often slowed. They are physically weak, in need of aid. Perhaps that is why we find it hard to put ourselves into that position; it isn’t a pleasant topic to think about. Four decades out into the future may as well be a science-fiction novel, a faraway land, a tale told to children, for all the influence it has on our present considerations. There is no weight to it.

When I am 85, there will have been next to no senescent cells in my body for going on thirty years. I bear only a small fraction of the inflammatory burden of older people of past generations. I paid for the products of companies descended from Oisin Biotechnologies and Unity Biotechnology, every few years wiping away the accumulation of senescent cells, each new approach more effective than the last. Eventually, I took one of the permanent gene therapy options, made possible by biochemical discrimination between short-term beneficial senescence and long-term harmful senescence, and then there was little need for ongoing treatments. Artificial DNA machinery floats in every cell, a backup for the normal mechanisms of apoptosis, triggered by lingering senescence.

When I am 85, the senolytic DNA machinery will be far from the only addition to my cells. I underwent a half dozen gene therapies over the years. I picked the most useful of the many more that were available, starting once the price fell into the affordable-but-painful range, after the initial frenzy of high-cost treatments subsided into business as usual. My cholesterol transport system is enhanced to attack atherosclerotic lesions, my muscle maintenance and neurogenesis operate at levels far above what was once a normal range for my age, and my mitochondria are both enhanced in operation and well-protected against damage by additional copies of mitochondrial genes backed up elsewhere in the cell. Some of these additions were rendered moot by later advances in medicine, but they get the job done.

When I am 85, my thymus will be as active as that of a 10-year-old child. Gene and cell therapies were applied over the past few decades, and as a result my immune system is well-gardened, in good shape. A combination of replacement hematopoietic stem cells, applied once a decade, the enhanced thymus, and periodic targeted destruction of problem immune cells keeps at bay most of the age-related decline in immune function, most of the growth in inflammation. The downside is that age-related autoimmunity has now become a whole lot more complex when it does occur, but even that can be dealt with by destroying and recreating the immune system. By the 2030s this was a day-long procedure with little accompanying risk, and the price fell thereafter.

When I am 85, atherosclerosis will be curable, preventable, and reversible, and that will have been the case for a few decades. There are five or six different viable approaches in the marketplace, all of which basically work. I used several of their predecessors back in the day, as well. Most people in the wealthier parts of the world have arteries nearly free from the buildup of fat and calcification. Cardiovascular disease with age now has a very different character, focused more failure of tissue maintenance and muscle strength and the remaining small portions of hypertension that are still problematic for some individuals. But that too can be effectively postponed through a variety of regenerative therapies.

When I am 85, there will be an insignificant level of cross-linking in most of my tissues, as was the case since my early 60s. My skin has the old-young look of someone who went a fair way down the path before being rescued. Not that I care much about that – I’m much more interested in the state of my blood vessels, the degree to which they are stiff and dysfunctional. That is why removal of cross-links is valuable. That is the reason to keep on taking the yearly treatments of cross-link breakers, or undergo one of the permanent gene therapies to have your cells produce protective enzymes as needed.

When I am 85, I will have a three-decade patchwork history of treatments to partially clear this form of amyloid or that component of lipofuscin. I will not suffer Alzheimer’s disease. I will not suffer any of the common forms of amyloidosis. They are controlled. There is such a breadth of molecular waste, however: while the important ones are addressed, plenty more remain. This is one of the continuing serious impacts to the health of older individuals, and a highly active area of research and development.

When I am 85, I will be the experienced veteran of several potentially serious incidences of cancer, all of which were identified early and eradicated by a targeted therapy that produced minimal side-effects. The therapies evolve rapidly over the years: a bewildering range of hyper-efficient immunotherapies, as well as treatments that sabotage telomere lengthening or other commonalities shared by all cancer cells. They were outpatient procedures, simple and quick, with a few follow-up visits, so routine that they obscured the point that I would be dead several times over without them. The individual rejuvenation technologies I availed myself of over the years were narrowly focused, not perfect, and not available as early as I would have liked. Cancer is an inevitable side-effect of decades of a mix of greater tissue maintenance and unrepaired damage.

Do we know today what the state of health of a well-kept 85-year-old will be in the 2050s? No. It is next to impossible to say how the differences noted above will perform in the real world. They are all on the near horizon, however. The major causes of age-related death today will be largely controlled and cured in the 2050s, at least for those in wealthier regions. If you are in your 40s today, and fortunate enough to live in one of those wealthier region, then it is a given that you will not die from Alzheimer’s disease. You will not suffer from other common age-related amyloidosis conditions. Atherosclerosis will be reliably controlled before it might kill you. Inflammatory conditions of aging will be a shadow of what they once were, because of senolytic therapies presently under development. Your immune system will be restored and bolstered. The stem cells in at least your bone marrow and muscles will be periodically augmented. The cross-links that cause stiffening of tissues will be removed. Scores of other issues in aging process, both large and small, will have useful solutions available in the broader medical marketplace. We will all live longer and in better health as a result, but no-one will be able to say for just how long until this all is tried.

Scott Emptage is an anti-aging activist in the United Kingdom. 

Induced Cell Turnover: A Proposed Modality for In Situ Tissue Regeneration and Repair – Press Release by Biogerontology Research Foundation

Induced Cell Turnover: A Proposed Modality for In Situ Tissue Regeneration and Repair – Press Release by Biogerontology Research Foundation

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Biogerontology Research Foundation


Scientists at the Biogerontology Research FoundationFeinberg School of Medicine at Northwestern University and Swammerdam Institute of Life Sciences at the University of Amsterdam have published a paper on a proposed method of in situ tissue regeneration called Induced Cell Turnover (ICT) in the journal Human Gene Therapy. The proposed therapeutic modality would aim to coordinate the targeted ablation of endogenous cells with the administration of minimally-differentiated, hPSC-derived cells in a gradual and multi-phasic manner so as to extrinsically mediate the turnover and replacement of whole tissues and organs with stem-cell derived cells.

“One of the major hurdles limiting traditional cell therapies is low levels of engraftment and retention, which is caused in part by cells only being able to engraft at locations of existing cell loss, and by the fact that many of those vacancies have already become occupied by ECM and fibroblasts (i.e. scar tissue) by the time the cells are administered, long after the actual occurrence of cell loss. The crux underlying ICT is to coordinate endogenous cell ablation (i.e. induced apoptosis) with replacement cell administration so as to manually vacate niches for new cells to engraft, coordinating these two events in space and time so as to minimize the ability for sites of cell loss to become occupied by ECM and fibroblasts. This would be done in a gradual and multi-phasic manner so as to avoid acute tissue failure resulting from the transient absence of too many cells at any one time. While the notion of endogenous cell clearance prior to replacement cell administration has become routine for bone marrow transplants, it isn’t really on the horizon of researchers and clinicians working with solid tissues, and this is something we’d like to change,” said Franco Cortese, Deputy Director and Trustee of the Biogerontology Research Foundation, and lead author on the paper.

Cell-type and tissue-specific rates of induced turnover could be achieved using cell-type specific pro-apoptotic small molecule cocktails, peptide mimetics, and/or tissue-tropic AAV-delivered suicide genes driven by cell-type specific promoters. Because these sites of ablation would still be “fresh” when replacement cells are administered, the presumption is that the patterns of ablation will make administered cells more likely to engraft where they should, in freshly vacated niches where the signals promoting cell migration and engraftment are still active. By varying the dose of cell-type targeted ablative agents, cell type and tissue-specific rates of induced turnover could be achieved, allowing for the rate and spatial distribution of turnover to be tuned to the size of the tissue in order to avoid ablating too many cells at once and inadvertently inducing acute tissue failure.

“Cell therapies are limited by low levels of engraftment, and in principle their ability to improve clinical outcomes is limited by the fact that they can only engraft at locations of existing cell loss. Conversely, therapeutic tissue and organ engineering requires surgery, is more likely to introduce biochemical and mechanical abnormalities to tissue ultrastructure through the decellularization process, and is fundamentally incapable of replacing distributed tissues and structures with a high degree of interconnectivity to other tissues in the body. The aim of ICT is to form a bridge between these two main pillars of regenerative medicine, extending the efficacy of cell therapies beyond a patch for existing cell loss and accomplishing the aim of tissue and organ engineering (i.e. the replacement and regeneration of whole tissues and organs) while potentially remaining free of some of their present limitations,” said Giovanni Santostasi, co-author on the paper and a researcher at the Feinberg School of Medicine, Northwestern University.

While future iterations of the therapy could use patient-derived cells, such as ESCs derived via somatic cell nuclear transfer (SCNT) or iPSCs derived from nuclear reprogramming, shorter-term applications would likely use existing stem cell lines immunologically matched to the patient via HLA matching. The authors contend that the cloning of adult organisms with normal lifespans from adult somatic cells testifies to the fact that adult cells can be rejuvenated and used to produce a sufficient quantity of daughter cells to replace the sum of cells constituting adult organisms, and that serial cloning experiments (in which this process is done iteratively, using an adult cell of each subsequent generation to derive the next) attests to this fact even more strongly.

“ICT could theoretically enable the controlled turnover and rejuvenation of aged tissues. The technique is particularly applicable to tissues that are not amenable to growth ex vivo and implantation (as with solid organs) – such as the vascular, lymphatic, and nervous systems. The method relies upon targeted ablation of old, damaged and/or senescent cells, coupled with a titrated replacement with patient-derived semi-differentiated stem and progenitor cells. By gradually replacing the old cells with new cells, entire tissues can be replaced in situ. The body naturally turns over tissues, but not all tissues and perhaps not optimally. I am reminded of the quote attributed to Heraclitus: ‘No man ever steps in the same river twice, for it’s not the same river and he’s not the same man,'” said Sebastian Aguiar, a coauthor on the paper and researcher at the Swammerdam Institute of Life Sciences, University of Amsterdam.

“Reversing aging in humans will require a multi-step approach at multiple levels of the organismal organization. In situ targeted ablation of the senescent cells and regeneration will be an important component of comprehensive anti-aging therapies,” said Alex Zhavoronkov, Chief Science Officer of the Biogerontology Research Foundation.

The researchers originally proposed ICT in 2016 in the context of biomedical gerontology as a possible means of preventing and/or negating age-related phenotypic deviation for the purposes of healthspan extension, and in this new paper they refine the methodological underpinnings of the approach, take a closer look at potential complications and strategies for their deterrence, and analyze ICT in the context of regenerative medicine as an intervention for a broader range of conditions based on disease or dysfunction at the cellular and intercellular level, with potential utilities absent from traditional cell therapies and tissue/organ engineering, the two main pillars of regenerative medicine. The intervention is still very much conceptual, and any potential utilities over other therapeutic modalities within regenerative medicine would need to be verified via preclinical studies, but their hope is to stimulate further research at this interface between geroscience and regenerative medicine.

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The paper is available here.

About the Biogerontology Research Foundation:

The Biogerontology Research Foundation is a UK non-profit research foundation and public policy center seeking to fill a gap within the research community, whereby the current scientific understanding of the ageing process is not yet being sufficiently exploited to produce effective medical interventions. The BGRF funds and conducts research which, building on the body of knowledge about how ageing happens, aims to develop biotechnological interventions to remediate the molecular and cellular deficits which accumulate with age and which underlie the ill-health of old age. Addressing ageing damage at this most fundamental level will provide an important opportunity to produce the effective, lasting treatments for the diseases and disabilities of ageing, required to improve quality of life in the elderly. The BGRF seeks to use the entire scope of modern biotechnology to attack the changes that take place in the course of ageing, and to address not just the symptoms of age-related diseases but also the mechanisms of those diseases.