2020’s journey to extending healthy human Longevity.
The journey to Longevity has many stages, whether it’s a clinical pipeline, gaining regulatory approval for a drug, or finding the appropriate collaborators to progress research. The Longevity field is a market in development, an iterative process dedicated to extending life one healthy year or month at a time.
Here are some of our favourite stories from 2020 that illustrate that journey.
The importance of geroprotectors in clinical trials
The Lancet launched its own journal on Longevity, publishing clinically-focused Longevity and healthy aging research; in the first edition, Dr Lynne Cox, et al., published a commentary calling for use of geroprotectors in clinical trials in older people especially in the context of COVID protection.
Dr Cox told us it is critical that we start using therapeutics shown to be effective through geroscience studies to improve the health and resilience of older people to infectious and other diseases. “We have come together as an international group of geroscientists and clinicians to call for older people, even those with significant pre-existing health conditions, to be included in clinical trials,” she explained, “and in particular for the rapid deployment of geroprotective drugs with good safety profiles that have already shown promise in older people with respiratory tract infections – drugs such as mTOR inhibitors, statins and metformin.
“There is also likely to be a role for senolytic drugs that selectively kill senescent cells in treating ‘long COVID’, particularly dealing with the lung fibrosis that appears to be a key pathological feature of COVID-19. Geroscience has a major role to play during a pandemic that hits predominantly older people the hardest.”
Biomarkers for Alzheimer’s Disease
As the world’s population ages, there is a focus on preventing and curing Alzheimer’s, and although Biogen’s aducanumab is moving a step forward to FDA approval, the National Institute on Aging and the Alzheimer’s Association are suggesting changes to the research definition of Alzheimer’s disease in order to better aid progress.
The criteria for defining what Alzheimer’s disease actually is for use in clinical trials and research would change to being defined by the presence of biomarkers, critical tools in drug development R&D, personalised healthcare and targeted therapies. Using these biomarkers to define Alzheimer’s would mean that sensitive clinical and neuropsychological assessments to help detect and track the early stage of the disease could be developed and refined and a model of Alzheimer’s disease progression over decades, from its earliest, pre-symptomatic stage right through to crippling dementia could be built.
Understanding the trigger for cellular senescence
Cellular senescence is a contributory factor in aging and its related diseases. Understanding it is the key to preventing it, rather just trying to reverse or ameliorate it. We were excited by a study by Sanford Burnham Prebys Medical Discovery Institute and Harvard University team that discovered that it is mitochondria, the powerhouses of cells, that trigger the zombie-like senescent state by communicating with the cell’s nucleus and that an FDA-approved HDAC inhibitor that is currently used as a cancer therapy, has the ability to transform senescent cells from their enlarged flattened state back to one that appeared younger and healthier.
“This study provides the first concrete link between several known hallmarks of aging – dysfunctional mitochondria, inflammation and senescent cells – which historically were studied as separate events,” said lead researcher Dr Peter Adams. “We are hopeful that targeting the molecular drivers of senescence will lead us to safe and effective medicines that help more people stay as healthy as possible, for as long as possible.”
Rapamycin moves closer to therapy
Will 2020 be remembered as the year in which the bacterial metabolite rapamycin began to edge ahead of the diabetes medicine metformin in terms of Longevity potential? A study identified that late‐life rapamycin treatment extended mouse lifespan and the ability of rapamycin to prolong survival has previously been shown in fruit flies.
Showing translation from mice to human studies is the next challenge, and AgelessRX is set to launch the Participatory Evaluation of Aging with Rapamycin for Longevity (PEARL) trial in collaboration with the University of California to systematically investigate the efficacy and safety of rapamycin use to promote Longevity.
“We’ll be doing close to $3,000 of testing per person,” Anar Isman, co-founder & CEO of AgelessRx told us about the IRB-approved PEARL trial. “This includes the Horvath clock and methylation peak testing, to see if rapamycin slows down your biological age.” We hope to report on the results next year.
Profiling plasma proteomes for Longevity
Understanding the profile of a plasma proteome creates a picture of protein expression in health and disease and the entire pathophysiological status of a living organism, leading to advances in disease diagnosis and therapeutic monitoring. The ability to detect and analyse proteins that are present at extremely low concentrations in plasma, coupled with the amount of the pathophysiological information it contains make the plasma proteome the ultimate target for biomarker discovery.
Two papers published this year furthered knowledge in the field, correlating proteins that were significantly associated with chronological age, demonstrating that the biology of aging overlapped with complex age-associated diseases and other age-related traits and deciphering the proteomic signature of frailty.
“It is important that biomarkers will distinguish biological age from chronological age,” Dr Barzilai told us, commenting on the papers. “If you take a test when you are 50 years old, but biologically you are only 40, you may not need a colonoscopy! It is even more important because biomarkers change with gerotherapeutics, so we know a therapy works as soon as possible without spending lots of resources. Proteomes like those in these papers reflect tissue breakdown are likely to change with any therapy, so they are great biomarkers to understand.”