I am thrilled and honored to podcast with Dr. Randy Jirtle. The field of epigenetics has exploded in the last decade, initiated almost exclusively by the groundbreaking research of Randy and his colleague Robert Waterland. Their 2003 study on the effects of nutrition on epigenetic gene regulation in agouti mice is the most cited paper in the history of science, and his trailblazing discoveries have expanded our understanding of human health and the etiology of disease. Listen to my fascinating conversation with Dr. Randy Jirtle.
Mike West: Stem Cells
Dan Pardi speaks with Dr. Mike West, CEO of AgeX Therapeutics. Here, we discuss a variety of important questions related to the science and potential of stem cells to positively influence human health including: The distinction between progenitor cells and stem cells; what goes wrong with stem cells during senescence; current clinical uses of stem cell therapies; what Dr. West’s team is working on at AgeX; and the future of stem cell therapies.
Aging is arguably the leading risk factor for chronic diseases in the modern world. We have historically thought of aging as an inexorable decline of function, driven by the passage of time – something that we simply have to accept, and that cannot be changed.
But what if aging were actually a modifiable risk factor?
Your chronological age, meaning the length of time that you have been alive, obviously cannot be changed. But we know that biological aging can vary significantly, even among individuals who are of similar chronological age. If we can better understand the fundamental mechanisms that underlie biological aging, we might be able to devise interventions that could prevent or delay age-related diseases.
One of the relevant processes is cellular senescence. Cellular senescence is a phenomenon through which normal cells irreversibly cease to divide in response to genomic damage. Senescent cells accumulate in the body as we get older, and they actually do a lot of bad stuff in the body. Senescent cells secrete pro-inflammatory factors, like cytokines, which induces a state of chronic low-grade inflammation. But it gets even worse. These senescent cells can also drive other healthy neighboring cells into senescence. So senescent cells are basically microscopic zombies!
This has driven interest in identifying senolytics – compounds that can selectively kill senescent cells (while leaving normal cells alone).
In this episode of humanOS Radio, Dan talks to Paul Robbins. Paul is the principal investigator at the Robbins Lab at Scripps Research Institute. Notably, his lab has been screening for drugs that can safely and effectively clear out senescent cells.
This research has produced some remarkable results in animal models. For example, he and colleagues found that older mice that were given senolytics became faster and stronger, and experienced a 36% increased median post-treatment lifespan, compared to a control group.
Davide D’Amico: Mitochondrial autophagy
We associate getting older with a loss of energy. On the molecular level, this is quite literally true, because one of the hallmarks of aging is mitochondrial dysfunction. Mitochondria are often referred to as “the powerhouse of the cell,” because they convert nutrients from the food we eat into usable energy, in the form of ATP. But as we age, mitochondria become less effective at generating the energy we need for various chemical processes.
So why does this happen? As with most things in biology, there are definitely multiple factors at work here. But one likely reason is a failure of quality control. As we age, mitochondrial autophagy (aka mitophagy) declines, and our body starts to accumulate broken and dysfunctional mitochondria. This becomes most obvious in tissues that consume a lot of energy, like skeletal muscle. Hence, mitochondrial dysfunction is linked to poor muscular strength in older people. If we could find a way to ramp up mitophagy, perhaps we could retain excellent mitochondrial function throughout our golden years.
In this episode of humanOS Radio, Dan Pardi welcomes Dr. Davide D’Amico to the show. Davide is a research scientist in the field of metabolism and aging. He was previously a post-doc at the Auwerx Laboratory of Integrative Systems Physiology at the École Polytechnique Fédérale de Lausanne (EPFL), where he investigated the role of mitochondrial function in health, disease, and the aging process.
Paleo: Interview with Michael Rose
Why do we age? The fundamental causes of aging at the molecular level are relatively well established. But the question of why aging happens in the first place is a more challenging one, one which has bedeviled evolutionary biologists and philosophers for years.
You might think, intuitively, that the process of natural selection would gradually eliminate senescence. Aging increases mortality, and organisms that experience impaired function and ultimately die would not be able to produce as many offspring as one that was able to live (and to reproduce) indefinitely, or at least for a much longer timespan. So, you would assume that this would result in selection for organisms that live much longer, generate more offspring, and ultimately the causes of age-related deterioration would fade from the genome. Yet aging is very commonly observed. Why is that?
Natural selection is strongest in early life. This makes sense – the natural environment is full of predators, disease, and other perils that often kill organisms when they are young and vulnerable. Consequently, genes and pathways that enhance survival and reproduction in early life are likely to be favored – even if they come at the cost of problems later in life, when selection is comparatively weak. But is aging inevitable? Can it be slowed, or postponed, or stopped altogether?
In this installment of humanOS, Dan Pardi talks with Michael Rose. Dr. Rose is a Distinguished Professor of Ecology and Evolutionary Biology at the University of California – Irvine. Rose’s laboratory has been testing the theory of antagonistic pleiotropy for nearly forty years, through artificial selection experiments in fruit flies.
In what was perhaps his most famous experiment, Rose allowed flies to only reproduce successfully if they laid their eggs late in life. He discarded the eggs of any flies that laid eggs before they reached a certain age. Over a few generations, this population of flies evolved longer lifespans. Why might this be? Remember that natural selection is strongest early in life, and becomes weak later on. In theory, if adults reproduce when they are older, natural selection is apt to favor genes that enhance resilience (and reproduction) later into the lifespan.
Dr. Rose’s research into aging has also drawn him to some interesting (and possibly controversial) notions about evolutionary changes in the human diet, and how our age may influence how adapted we are to modern agricultural foods.
Why is that we tend to see many diseases of aging occur around the same time in life? One reason is that we accumulate senescent cells with age, and these cells promote the aging process. There is, however, exciting new research that shows how these cells can be cleared as we age. Some of the compounds are drugs but others are natural compounds that could have a meaningful effect.
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