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Category Archives: David Sinclair

Cancer. How close are we to winning the war? – Switzer

When I started my medical degree in the 1970s, a diagnosis of cancer was typically a death sentence. Occasionally, if cancer was detected early, there was some hope for surgical resection. The radiotherapy and chemotherapy used back in those days was rather primitive and certainly often extremely toxic to the body.

Now in the year 2020, despite significant emphasis being appropriately placed on improved therapies and vaccines for COVID-19, the medical world is closing in on a cure for cancer. Over the past decade, the widespread use of immunotherapy and the somewhat newer CAR-T therapies & their spinoffs have revolutionised the treatments of many cancers including haematologic cancers, such as leukaemia and lymphoma but also the common solid tumours such as breast, prostate, colon, lung and melanoma, to name a few.

One of the issues with cancers is that they form a shield around individual tumour cells making them almost invisible to the immune system. Many of the newer immunotherapies help break down the shield, allowing the bodys own immune system to attack the tumour cells.

One of the best group of tumour killing cells in the immune system are T cells known as Tumour Infiltrating Lymphocytes (TILs). Although these are probably the best soldiers of the immune system, once they enter the battlefield of the tumour micro-environment they are disabled by many of the stressors present in this situation. All cells, whether they be our own naturally occurring cells or those of tumours that have formed in our body, require a supply of nutrients and oxygen to function correctly.

Thus, when a TIL enters a tumour to do its work, it is competing with the tumour for local nutrients and oxygen. The tumour being extremely greedy steals these nutrients leading to a reduction in the function of a component of all cells known as the mitochondria. Mitochondria are the fuel supply of the cell creating energy for the cell, allowing it to do its work and exist. If we deprive the mitochondria of nutrients, the mitochondria are converted into a sluggish state known as terminal exhaustion. Also, when the T cells mitochondria are starting to age, there is a natural process that breaks down the cells and replaces them with younger, healthier T cells to continue the job of trying to destroy any tumours that are present.

The function of any living cell, including T cells and tumour cells, is to survive. Cancer cells create particular antigens which stimulate a protein known as PD-1, which suppresses the T-cell response. Thus, when you have cancer, there is this constant battle being waged inside your body between your own immune system and the tumour.

Now for the good news. Scientists from the US have discovered that a commonly used supplement for anti-ageing known as NAD-riboside enhances mitochondrial function in these failing T cells and allows them to recharge themselves to enhance their attack against tumours. When NAD-riboside was added to specific immunotherapy drugs, this significantly inhibited the growth of a variety of tumours in mice.

Professor David Sinclair from Harvard University has pioneered the use of NAD-riboside for anti-ageing demonstrating that this is a safe and effective supplement, prolonging the life of laboratory animals by 20%. Prof Sinclair has also demonstrated the same anti-ageing markers in human beings. There now appears to be another feather in the cap for this safe and seemingly effective supplement, which may become standard care to be added to all new cancer therapies.

A word of caution in that this has not been trialled in humans as additional therapy but, many people, including myself, already take NAD-riboside or a related supplement e.g. NMN; NAD plus, as a potential anti-ageing therapy. I have been saying for a number of years that vitamin B3 and its variety of analogues such as NAD-riboside are a vital part of good health. This is yet more evidence to support these claims. Although we have not achieved a cure for cancer in 2020, we are certainly edging closer.

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Brexit casts doubt over UK pension rights – Interactive Investor

Future retirees are facing uncertainty over the level of state pension they will receive if they move abroad and could miss out on around 140,000 of income once the Brexit transitional period ends, Aegon claims.

The pension company is warning that the outcome of Brexit negotiations could have a huge impact on the retirement prospects of UK citizens who plan to move to and retire in the European Union (EU) or Switzerland.

Currently, those who are already living in the EU before 31 December 2020 have been reassured that they will receive the same increases to UK state pensions as paid to those living in the UK.

This is based on the triple lock, which guarantees the state pension will rise by the highest of earnings growth, price inflation or 2.5% each year.

However, aside from those who move to Ireland, there has been no guarantee from the UK on the level of the state pension for those retiring and living in other countries.

Steven Cameron, pensions director at Aegon, says: The outcome of last-minute Brexit negotiations could have a huge impact on those who may be planning to retire abroad to another EU country.

With many people living 20 or more years after state pension age, any form of inflation proofing is highly valuable, with the triple lock particularly so.

An inflation linked state pension of 175.20 a week is worth 336,500 whereas one that doesnt increase is worth 191,000 which is 145,500 less.

Cameron adds that while the treatment of state pensions may not be top of the agenda for last minute Brexit negotiations, he warns decisions in these areas could make a huge difference to those planning to move abroad in future for their retirement years.

David Sinclair, director of thinktank the International Longevity Centre, says: For some older people, the state pension provides a significant part of their retirement income.

These people in particular will want to be confident that they can afford their retirement aspirations irrespective of whether they stay in the UK or move abroad.Older people who want to move abroad need to be confident that value of their savings alongside their pension will be adequate.

Sinclair adds that retirees will need to make their wealth last 20-plus years and says this uncertainty is unhelpful for those who want to plan for the long term.

These articles are provided for information purposes only. Occasionally, an opinion about whether to buy or sell a specific investment may be provided by third parties. The content is not intended to be a personal recommendation to buy or sell any financial instrument or product, or to adopt any investment strategy as it is not provided based on an assessment of your investing knowledge and experience, your financial situation or your investment objectives. The value of your investments, and the income derived from them, may go down as well as up. You may not get back all the money that you invest. The investments referred to in this article may not be suitable for all investors, and if in doubt, an investor should seek advice from a qualified investment adviser.

Full performance can be found on the company or index summary page on the interactive investor website. Simply click on the company's or index name highlighted in the article.

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100 years old will be the new 60 | Health & Wellness – CL Charlotte

For the first time in history, leading scientists and entrepreneurs believe theres a way to slow aging and maybe even reverseit.

The latest research on longevity suggests there is no reason that people born today cant live to at least 120 years old... perhaps even to 150 and beyond.

How would you change your life if you could live to 120 years old and remain healthy?

What would you do differently today?

Last week we explored the Longevity Mindset. Today and next week, Ill do a quick review of the latest advancements toward rewiring the biology of aging.

Every year, I take a group of my Abundance 360 Members on a Platinum Longevity Trip to meet with the cutting-edge researchers and companies. Following are some of the companies and technologies we observed that have the potential to increase your healthspan the amount of time you have to live a healthy and functional life, avoiding expensive end-of-life care.

Todays blog will be part one of a two-part series covering these developments.

Lets dive in

Over the past two decades, the cost of sequencing the human genome has dropped 100,000-fold: from $100 million per genome, to below $1,000 per genome (current estimates are as low as $300).

Genome sequencing can uncover disease susceptibilities years before symptoms present, allowing for personalized preventative care to begin sooner than ever before.

For example, the Cancer Genome Atlas Program at the NIH is currently using gene sequencing to decode the genetic underpinnings of 30 cancer types.

Perhaps the most impactful potential of low-cost genome sequencing is its ability to be used in what is called a liquid biopsy the ability to find free-flowing cancer DNA in your bloodstream that might indicate the existence of an undetected cancer in your body. And, as we know, finding cancer at stage-zero or stage-one is the key to survival.

There are two major companies we visited with during our Platinum Longevity Trip:

Cancer detection company GRAILanalyzes the mutated, fractionated DNA and RNA from cancer cells in your blood (from a simple blood draw) to diagnose over 50 cancer types in early stages. GRAIL recently received an $8 billion buy-out offer from biotech giant Illumina.

Freenometakes a similar approach to early cancer diagnosis from a real-time blood draw (called a liquid biopsy), initially focused on colon cancer. Freenomes multiomics platform analyzes fragments of DNA, RNA, and protein from the cancer and from the host response. This form of precision medicine bridges early detection and early intervention to boost human healthspan.

One of the most powerful technologies now available in the fight for longevity is called gene therapy a technology theorized in the 1980s that has taken almost 40 years to mature. Gene therapy allows scientists to use a vector (typically an Adeno Associated Virus) to carry a desired gene to a set of desired cells in an organism. Want a specific gene put into retinal cells, or bone marrow, or neurons? No problem, there's a gene therapy approach for that.

A new biotech start-up called Gordian Biotechnologyis using the convergence of gene therapy and single cell sequencing to run hundreds of thousands of independent experiments in a single animal to determine the therapeutic effects of specific gene additions on specific cells of interest. Because aging is such a multifactorial process, this approach can run thousands of parallel experiments to tackle the many complexities of age-related diseases simultaneously.

Next week, well learn about a company called Rejuvenate Bio, and an extraordinary researcher named Dr. David Sinclair who is using gene therapy to potentially rejuvenate animals with the ultimate goal of age reversal in humans.

In addition to Gene Therapy, the other incredible tool in our longevity research arsenal is CRISPR.

You may know CRISPR as the molecular scissors that can edit genes think CTRL X (cut) and CTRL V (paste). But beyond cutting and pasting, CRISPR can also be used to help find and identify a sequence of DNA in your cell, sort of a CTRL F functionality. This discovery is so important and transformative that the Nobel Prize was just awarded this month to Dr. Jennifer Doudna of Gladstone Institutes for its discovery.

Here are several other exciting CRISPR developments:

Gladstone-UCSF Institute of Genomic Immunologyis using CRISPR to edit the T-cells of the immune system that play critical roles in cancer, infection, and autoimmunity. CRISPR can delete mutated genes or add new DNA to reprogram the T-cells. This personalized approach takes advantage of the bodys own immune system to tackle complex diseases.

Rather than snipping and replacing genes, Mammoth Bioscienceshas programmed CRISPR proteins to locate and cleave target genes, acting as molecular shredders. The cleaved gene serves as a molecular readout if the target is successfully bound, enabling CRISPR to serve as a diagnostic tool. Additionally, the companys novel CRISPR proteins (cas14, casV) exist in the micro and nano scales, opening the door for new delivery systems at smaller scales than ever before.

With the recent breakthroughs in CRISPR and Gene Therapy technologies, a variety of strategies for reversing disease have been tried. Yet countlessexperiments remain, and thats where AI can help.

The explosion of novel imaging, sensing, and sequencing tools has unleashed an abundance of patient data.

But bringing together this information across millions of patients to form actionable insights can only be achieved with Artificial Intelligence.

One of the leading companies in this area is Insilico Medicine, which is leveraging AI in its end-to-end drug pipeline, extending healthy longevity through drug discovery and aging research.

In their comprehensive drug discovery engine, Insilico uses millions of samples and multiple data types to A) discover signatures of diseases, and B) identify the most promising targets for billions of molecules. These molecules either already exist or can be generated de novo with the desired set of parameters.

Insilico uses an AI technique called generative adversarial networks (GANs) to imagine novel molecular structures. With reinforcement learning, Insilicos system lets you generate a molecule with any of up to 20 different properties to hit a specified target.

Thanks to converging breakthroughs in machine learning, drug discovery and molecular biology, companies like Insilico can now do with 50 people what the pharmaceutical industry can barely do with an army of 5,000.

Another extraordinary company on the Longevity Platinum Trip was a company out of the Buck Institute called Edifice Health, which has developed the ability to determine your inflammatory age using advanced AI to score biomarkers of immune health. Inflammation is a leading contributor to most chronic illnesses, and greater awareness of this symptom will enhance preventative care. Even more important than measuring inflammatory age, Edifice Health is screening thousands of molecules to determine which can quell such inflammation.

An additional company out of the Buck Institute is Gerostate Alpha, a pharmaceutical company that is using large-scale AI to test millions of compounds for their ability to extend the life of a worm-like creature called the nematode. Once they get a hit in nematodes (rather short-lived creatures), they will then test the molecules in mice and eventually in humans. The company is testing millions of compounds in parallel, hoping to literally discover the pharmaceutical fountain of youth.

In next weeks blog, well continue to review other exciting companies on the cutting-edge of longevity science, diving more into gene therapy, senolytic medicines, vaccines, and stem cells.

If tracking the latest breakthroughs in longevity is something you desire If developing a Longevity Mindset is important to you, then consider joining my Abundance 360Mastermind.

Every year, my team and I select a group of 360 entrepreneurs and CEOs to coach over the course of a year-long program. A360 starts each January with a live event and continues every two months with Implementation Workshops, in which I personally coach members in small groups over Zoom. (In January 2021, you have a choice of live in-person or virtual participation. See the A360 website for more info.)

My mission is to help A360 members identify their massively transformative purpose, select their moonshot, and hone an Abundance, Exponential, and Longevity Mindset. Together we will actively select and reinforce your preferred mindsets.

To learn more and apply, visit abundance360.com

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How newly unemployed over-50s can start-up again – The Guardian

Max Wallace, a former professional boxer with an interest in art, wants to set up his own wellbeing centre. Sunil Jindal plans to set up a Mumsnet for older men while Sharon Thomas has a business model to monetise her mini artwork greetings cards.

But these entrepreneurs face one problem: theyre over 50 and although the state pension age rises to 66 on Tuesday, 54-year-old Jindal said they already risk being perceived to be over the hill by everyone from banks to, occasionally, themselves.

Ive had a very successful career in computer science, reaching director level, but when my last employer and I went our separate ways in July, I found it a real shock to be back in the job market, Jindal said.

Im applying for jobs but Im planning my own business too because I cant help asking myself: Will I find something at my age? Theres so much stigma around older people out there and I find I doubt myself too; can I reposition my USP at my age, deal with the technology, sustain the energy? he added.

Wallace has no shortage of energy, having set up a community interest company called Health Defence which offers fitness programmes, aimed at combatting ill health in the community. He now hopes to open a micro wellbeing centre in Hammersmith, west London, where people can access his boxing/kickboxing fitness programme, along with healthy eating workshops, massages and free health checks.

Around 377,000 older workers one in 10 male, and eight in 10 female workers in their 50s and 60s face a significant risk of losing their jobs as the governments furlough scheme is wound down this month, according to the Centre for Ageing Better and the Learning and Work Institute.

That is in addition to the recent doubling in the number of people over-50s already claiming unemployment-related benefits between March and May. According to an analysis of official data by Rest Less, a jobs, money and lifestyle site for the over-50s, numbers rose from 304,000 in March to 588,000 in June. This means that more over-50s are claiming universal credit than under-25s.

Additional analysis of Department for Work and Pensions data by the Centre for Ageing Better found that over-50s are less likely to bounce back from unemployment than any other age group: just 35% who lose their job return to work quickly, with 29% remaining unemployed for more than 12 months.

These statistics are causing concern among experts. Last week, the International Longevity Centre UK (ILC), the UKs specialist thinktank on the impact of longevity on society, urged the government to introduce a scheme akin to Kickstart but focused on the needs of older workers.

The long-term growth in employment of those aged over 50 has stalled, with too many people forced out of the workforce too early, said David Sinclair, ILC director. These older workers contribute to economic growth but are likely to find it much more difficult than other ages to get themselves another job.

Andy Briggs, group CEO at Phoenix Group and Government Business Champion for Older Workers, agreed. We know that if you become unemployed over the age of 50 you are less likely than any other group to get another job.

Suzanne Noble, who co-founded Advantages of Age with Rose Rouse, said this is a problem for which there are limited solutions. Noble, who has co-founded the Startup School for Seniors which launched on Monday, said a move into self-employment is one of the most positive and realistic choices available.

Lack of confidence is the key challenge for this age group, said Noble, who has also launched Silver Sharers, a website that matches homeowners aged 50-plus with lodgers of any age. We know, from previous work done with over-50s, that when an older person loses their job it can take a real toll on their mental health.

If youve been working for decades in a career, the expectation is that will deliver you into a comfortable retirement, she added. When that outcome is taken away from you, it can be crushing. Many feel that their work experience no longer has any value and that theres nowhere for them in the modern workplace.

But thats simply not the case, said Noble. Experience is one of the most important USPs of this group, so ignore it at your peril, she said. We have a more relaxed attitude to other people and their opinion about us: the No Fucks Given-movement stole the idea from their elders and betters.

The statistics show the value of that experience: businesses started by those aged over 45 are more likely to be successful than those created by those aged 18-25 years.

Mark Elliott, Nobles co-founder of the free, eight-week online Startup School for Seniors whose 60 participants are aged between 50 to 75 pointed out that modern technology is easier to use than it ever has been. If Covid-19 has taught us nothing else, its that many more older people have become digitally savvy through using Zoom and other video conferencing software, he said.

Theres no reason to assume that someone 50-plus hasnt got the aim or ambition of building a fast-scaling tech business but older entrepreneurs need to be realistic, he said.

Theyre not going to suddenly become Richard Branson but then, would they want to? he asked. On top of what opportunities there are, is the extra question, what sort of opportunities are people this age usually looking for?

With one in five people over 50 being informal carers, flexibility is key, said Elliott. Added to which, older people are often seeking a job that provides them with satisfaction as well as a pay cheque. At this stage in our lives, we need to build a business that we want to work in ourselves. Thats exciting.

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Immetas Therapeutics Announces Series A Financing to Advance Research on Inflammation Pathways in Aging and Develop Therapeutics for Cancer and…

EAST HANOVER, N.J.--(BUSINESS WIRE)--Immetas Therapeutics today announced it has raised a Series A financing of $11 million to advance research on inflammation pathways in aging and the development of novel, immune modulating treatments for cancer and inflammatory disease. Morningside Ventures was the sole investor in the financing round.

Morningsides investment is a significant endorsement of our approach to targeting inflammation pathways in aging and our clinical evidence-based discovery strategy, said J. Gene Wang, MD, PhD, co-founder and CEO. Emerging research that molecular pathways driving both aging and age-related diseases converge around chronic, low grade inflammation is creating a new set of opportunities to treat cancer and other serious diseases. Immetas is well positioned to capitalize on these new advances.

Dr. Wang added, Our approach prioritizes clinical evidence and a deep interrogation of disease mechanisms to guide drug discovery. This strategy is designed to reduce development risk resulting from the translational gap between laboratory findings and patients and ensure the development of superior and well-differentiated drugs.

Dr. Wang co-founded Immetas after a 20-year career at large pharmaceutical companies, including Merck, Abbott, GSK and Novartis, where he played integral roles in the successful development of major drugs, including Humira (adalimumab), Varubi (rolapitant), Zolinza (vorinostat) and Gardasil (human papilloma virus vaccine), and led multiple programs from discovery to clinical proof-of-concept. Dr. Wang received his M.D. from Peking University Medical Center and Ph.D. in Immunobiology from Yale University, followed by medical residency training at Yale New Haven Hospital.

Immetas other co-founder, Dr. David Sinclair, is an internationally recognized scientist known for his research on genes and small molecules that delay aging, including Sirtuin genes, resveratrol and NAD precursors. He was among TIME magazines 50 Most Influential People in Healthcare in 2018. Dr. Sinclair is Professor of Genetics at Harvard Medical School and co-Director of the Paul F. Glenn Center for Biology of Aging Research at Harvard and he serves as a science advisor to the Company.

We have a shared vision that inflammation is the fundamental and ultimate process driving aging and age-related cancers and inflammatory diseases, said Dr. Sinclair. Our approach is distinct from others that have targeted conventional age-related pathways and to date have proved challenging.

The Company is building a pipeline of biologic and small molecule drugs internally and through collaborations. Immetas lead program is aimed at designing a series of bi-specific antibodies to regulate inflammation in the tumor microenvironment and overcome resistance to conventional immune checkpoint therapies.

In connection with the financing, Dr. Lu Huang, MD, MBA, Managing Director at Morningside Ventures, joined the Immetas board of directors. Since joining Morningside in 2003, Dr. Huang has led nearly three dozen healthcare / life science investments in China and the United States.

About Immetas TherapeuticsImmetas discovers and develops novel therapeutics that modulate the innate immune system to treat age-related cancers and inflammatory diseases. The companys approach is based on emerging evidence that chronic low-grade inflammation is a fundamental process governing aging and age-related diseases and anchored in clinical evidence to mitigate development risk. Immetas was founded by J. Gene Wang, MD, PhD, a veteran in discovery and translational drug development in immunology/ inflammation and oncology, and David Sinclair, PhD, Professor of Genetics at Harvard Medical School and a leader in the molecular mechanisms of aging. The lead program in the companys growing pipeline is focused on engineering bispecific antibodies to modulate inflammation in the tumor microenvironment and overcome resistance to the conventional immune checkpoint therapies. Learn more at http://www.immetas.com

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DS4 to rock Morden live at The Sound Lounge – Your Local Guardian

After their shows were cancelled due to the pandemic, DS4 will return to music by headlining at The Sound Lounge this weekend.

Rock band DS4 is set to headline at the grassroots music venue in Morden on Saturday September 25.

The audience at the Sound Lounge can expect a "rock and roll show with a vintage touch" between 7.00 pm to 9.30 pm.

Singer, songwriter and guitarist David Sinclair,says the performance is the groups lifeline.

DS4 came together when David Sinclair hooked up with guitarist Geoff Peel, a sage of the London blues circuit.

Together with Jos Mendoza, ex bass player Jack Sinclair and a cast of special guests, they recorded the album 4 in 2015. Gigging around London venues, including The Borderline, 100 Club and Half Moon Putney, and festivals such as Cornbury and North Wales Blues and Soul Fest, the DS4 has built up a dedicated following.

And won glowing testimonials for a show full of good time rock and roll energy, stirring personal blues ballads and wry narrative wit.The band featuring drummer Rory, has sold-out gigs at the Crawdaddy Club in Richmond, Dustys Blues Club in High Wycombe, Portobello Live and Gunnersbury Triangle Club.Their latest album Sweet Georgina has received ecstatic reviews, with their track 'The Rolling People' featuring on the CD covermount of Classic Rock magazine last year.

With years of entertaining and months of having to stay inside, the band are "over the moon" to be back in front of an audience.

A spokesperson for DS4 said: "The Sound Lounge can look forward to a glorious show featuring original songs from our first five albums.

"Mixed with classic covers of songs by Lou Reed, Chuck Berry and the Red Hot Chili Peppers.

"Live performances are the oxygen that keeps a band like us alive.

Its been a long time to manage without it, and this show is a lifeline for us.

"Zoom and Spotify are all very well.

"But we just cant wait to make contact with hearts and minds in the outside world again.

For ticket information visit http://www.thesoundlounge.org.uk/whats-on

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