Writing this blog has introduced me to a community (that\u2019s you) with which I have shared a great deal of information, and from which I have learned more. \u00a0You have become dear to me. \u00a0Now I\u2019ve been away for many weeks, away from my home (Philadelphia) and away from this blog. \u00a0I\u2019ve been in California and Switzerland and (now) China. \u00a0Here are some snippets of what I\u2019ve learned and what I\u2019ve been thinking.<\/p>\n
My mother was proud of me when I was a physicist, but since I took up the study of aging she only shakes her head and stops just short of calling my work immoral. \u00a0She has been a lifelong advocate for population control and family planning. \u00a0\u201cThere are already too many people in the world. \u00a0When people started living longer, the population started booming.\u201d<\/p>\n
She is 95, posts a living will on her refrigerator, in her purse and in her car. \u00a0She wears beaded jewelry that says, \u201cDo Not Resuscitate\u201d. \u00a0But when she had a stroke last month, a neighbor called 911, and the medics did what they are trained to do. \u00a0I spent several weeks by her bedside, and making arrangements for her rehabilitation and physical therapy. \u00a0Her mind and speech seem unaffected, but she sees it as a grave injustice that she is still alive.<\/p>\n
This has been an opportunity for me to examine my attitudes toward death and the prejudices of my culture. \u00a0Still raw, I have only questions, not answers\u2026<\/p>\n
My encounter with hospitals and insurance served to instantiate and reinforce my dim views of the American system. \u00a0Limitation of liability everywhere impedes effective care for individuals. \u00a0\u201cWhat is covered\u201d is more important than \u201cwhat is best for the patient,\u201d and coverage is maddeningly arbitrary and variable from one policy to the next. Doctors, by and large, are kindly with the best of intentions, but their brains are fried by quotas and schedules; they have no time to work with a patient, to listen to symptoms, to explore diagnostic possibilities and treatment options. \u00a0Most know less about diet, exercise and supplements than you do, dear reader. \u00a0Hospitals will do everything to keep the patient from dying on their watch, but nothing to put individuals under their care on a path to long-term health and wellbeing.<\/p>\n
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Back to Biology<\/b><\/p>\n
While in California for my Mom, I had a chance to make three visits to colleagues in the biology of aging.<\/p>\n
From Andy Mendelsohn<\/a>, I learned that a stem cell can be made to differentiate into a particular kind of somatic cell by one or a few transcription factors. Furthermore, you don\u2019t have to start with a stem cell; applying these same factors to a different kind of somatic cell re-directs it toward the target of the transcription factors. \u00a0For example, applying the nerve cell TFs to a skin cell can turn a skin cell into a nerve cell. \u00a0Andy raised the possibility that this re-programming process is rejuvenating. \u00a0What would happen if you applied the skin cell TFs to an old skin cell? \u00a0Would it become a young skin cell? \u00a0This is an area ripe for experiment!<\/p>\n Andy also reminded me of a topic I wrote about 4 years ago<\/a>: the hypothalamus as an endocrine aging clock, and the role of inflammation in suppressing two anti-aging hormones, to wit, GnRH and NPY (gonadotropin-releasing hormone and neuropeptide Y). \u00a0If there is a centralized clock at the root of aging, the hypothalamus is currently our best candidate for its location [ref<\/a>, ref<\/a>]. \u00a0Both these are small proteins. \u00a0NPY has a short residency time in the blood, and there is yet no practical way to increase its level, but GnRH is normally released in pulses, and might it might be easy to enhance these artificially; in fact, there are several synthetic variations of GnRH<\/a> sold as drugs. \u00a0The fact that they suppress male sexuality is a deterrent to experimentation by most men.<\/p>\n I learned that Elissa Epel<\/a> has begun a long-term project to collect and share data on lifestyle habits for health and longevity. \u00a0She plans to develop a cell phone app both to remind and encourage and also to record metabolic responses. \u00a0Users will be able to learn what is working for their own individual bodies, and to share information so that others can benefit from their experience. \u00a0For Epel as a researcher, the payoff is crowdsourced data from which to study correlates of good health and long life. \u00a0I signed up on the spot to be her statistician. TrackYourLyf.com<\/a> is under development.<\/p>\n The third visit was with Mike and Irina Conboy – see below.<\/p>\n <\/p>\n Geneva Symposium on Anti-aging Medicine<\/b><\/p>\n I was honored to be invited to a small symposium in Geneva<\/a> last week, sponsored by the St Petersburg laboratory of Vladimir Anisimov and Vladimir Khavinson. \u00a0I spoke on my favorite topic these days<\/a>: the potential value of quick-and-dirty screening for combinations of age treatments that might synergize to induce major increases in lifespan. \u00a0I proposed<\/a> a medium-scale experiment with 1300 mice that would test all combinations of 3 treatments among a pre-selected universe of 15. This size of experiment seems to be a statistical sweet spot for combinatorics.<\/p>\n The most revealing talk from my vantage was Claudio Franceschi<\/a>\u2019s glimpse into broad effects of the gut microbiome, a topic which I\u2019ve written about recently<\/a>. \u00a0Diversity of our intestinal flora decreases with age. \u00a0Centenarians seem to have different microbiomes from the rest of us, with an enhanced role for allochtonous flora<\/a>, which just means niche-adapted bacteria [ref<\/a>]. \u00a0We are used to thinking of allochtonous\u00a0bacteria as associated with infections and pathology. \u00a0They prompt an inflammatory response in the host (that\u2019s us) to a greater extent than other bacteria. \u00a0Why would there be more of these in centenarians?<\/p>\n There is a powerful interaction between the microbiome, the immune system, the endocrine system, and the central nervous system [ref<\/a>]. \u00a0Presently, high fiber diets are the only generally-agreed path toward healthy microbiomes. \u00a0Fecal transplants<\/a> and probiotics are of uncertain value with respect to long-term health. \u00a0Here\u2019s a paper from 6 years ago<\/a> in which a particular strain of yoghurt bacteria (LKM512<\/a>) was introduced into intestines of mice with dramatic effect on their mortality. \u00a0The field is developing rapidly now that people appreciate how important it is.<\/p>\n Given the sponsors of the one-day symposium<\/a>, I was not surprised to see an emphasis on short peptides. \u00a0These are micro proteins, just 3 or 4 amino acids strung together, that have been studied in St Petersburg with remarkable results: extension of lifespan in mice, and halving the mortality rate among older experimental subjects who receive peptide supplements. \u00a0Why isn\u2019t anyone trying to replicate these studies in the West? \u00a0Khavinson has leapt ahead to open a clinic in St Petersburg<\/a>\u00a0where various peptides are prescribed for various ailments, and one of the peptide docs has a satellite clinic in Italy. \u00a0I met an American doctor<\/a> who runs a clinic in Alaska where you can buy oral versions of epitalon and other peptides from a British company<\/a>. \u00a0But the British web site does not list chemical compositions of their brand-name peptides, and though Dr Lawrence is full of enthusiasm and anecdotes, there is no data nor plan to collect data on their effectiveness in humans. \u00a0To my mind, this is a case of commercialism leaving science behind.<\/p>\n Which brings me to one more topic…<\/p>\n <\/p>\n Plasma Transfusions for Rejuvenation, Ready or Not<\/b><\/p>\n In the news this week<\/a> is Ambrosia, Jesse Karmazin\u2019s company which provides transfusions of blood plasma from young donors to old recipients, who pay about $8,000 for 1.5 liters of blood. \u00a0When I first spoke with Karmazin nearly two years ago, he told me he had analyzed Stanford Hospital data on hundreds of patients who had received transfusions for various reasons. \u00a0He made the remarkable claim that he was able to trace the source of the blood in these transfusions, and found that patients who had received transfusions from young donors had had lower mortality and significantly better outcomes than those who had been paired with older donors. \u00a0This is an impressive finding if true, but Karmazin refused to share his data with me, claiming \u201cpatient privacy\u201d, even if all personal identifiers were redacted. \u00a0At the time, he said that his motivation was to boost research in the field, that plasma transfusions were already an approved procedure and needed no special FDA approval, and that he thought he could fund the project by charging costs to the experimental subjects. \u00a0When I exchanged emails with him this week, he said that the data generated by his company would be treated as \u201cintellectual property\u201d and not shared openly with the scientific community.<\/p>\n My opinion is that, based on mouse studies, plasma transfusions are a promising procedure, but we have yet to explore how much is needed, the frequency and severity of complications, what are the benefits and how long they last. \u00a0A medium-sized body has about 5 liters in circulation. \u00a0Is 1.5 enough to make a difference? \u00a0That these experiments will be done is a huge step forward, but the benefit depends on data that is made available to the scientific community. \u00a0If the result is dramatic age reversal, we will all know about it pronto. \u00a0But if (more likely) the result is nuanced, we might be starved for balanced information.<\/p>\n One other company experimenting with human subjects is Alkahest, founded by Tony Wyss-Coray of Stanford. \u00a0Alkahest has received approval<\/a> to do a trial with early-stage Alzheimer\u2019s patients, using 2 liters of blood from a young donor, spread over 4 weeks. \u00a0The endpoints they will be examining involve cognitive function.<\/p>\n Wyss-Coray has voiced scathing charges<\/a> of irresponsibility against Ambrosia. \u00a0Meanwhile, Berkeley\u2019s Irina Conboy (in a private conversation last month) has been highly critical of Alkahest. \u00a0It was Conboy who originally brought the idea of parabiosis experiments to a Stanford lab<\/a> 15 years ago, where she and her husband Mike and Wyss-Coray and Amy Wagers (now at Harvard) were all students together. \u00a0She said that Alzheimer\u2019s was the wrong target, that the amount of blood being provided would not be enough to make a difference, and that repeat transfusions exposed patients to the risk of anaphylactic shock if some patients\u2019 immune response to the alien proteins got out of hand.<\/p>\n The Conboys have been working on isolating the active ingredients that make old blood harmful and young blood beneficial. \u00a0I asked how that work was progressing. \u00a0While they would not share details, they said that early hopes for a small, manageable number of active factors had not panned out. \u00a0They were hopeful, however, that all the necessary factors belong to a few major pathways, and that transcription factors could be identified that would selectively activate these pathways. \u00a0From a New Scientist article<\/a>:<\/p>\n Older people who received transfusions of young blood plasma have shown improvements in biomarkers related to cancer, Alzheimer’s disease and heart disease. Since August 2016, Ambrosia has been transfusing people aged 35 and older with plasma – the liquid component of blood – taken from people aged between 16 and 25. So far, 70 people have been treated, all of whom paid Ambrosia to be included in the study. The first results come from blood tests conducted before and a month after plasma treatment, and imply young blood transfusions may reduce the risk of several major diseases associated with ageing.<\/em><\/p>\n