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1 day ago · And though aging while still young has forever been a silly topic for Smith, the now-65 Cure curator has caught up to his epoch years during the 10-minute long “Endsong.” Rather than reminisce, Smith remembers the “hopes and dreams” of a not-so-lost world — all he had and all that he set out to do — bittersweetly.
Jul 15, 2023 · Reversing methylation doesn’t cure aging. Even if we can control senescent cells, extend telomeres, restore healthy mitochondria, and restore the thymus gland. None of the aging scientists have a plan for repairing DNA errors.
This paper highlights important clinical implications for the use of reminiscence as a therapy for older adults. The life review process is a meaningful part of late-life well-being, and understanding factors that impede it can facilitate both the treatment of depression and anxiety and their prevention.
Oct 1, 2014 · Reminiscence therapy is an evidence-based treatment for geriatric depression. This chapter reviews the literature on the definition of reminiscence and its use as a therapy for older adults. It also reviews the evidence for the efficacy of various types of reminiscence therapies for older adults with dementia and depression.
- Overview
- Clearing out the zombies
- Table 1 | Selected companies targeting senescent cells
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Delaying aging, restoring youth, regenerative medicine… whatever term is used, research aiming to target fundamental mechanisms of aging to increase life expectancy and quality has flourished in recent years.
Over time, processes such as DNA damage, infection, and oxidative stress can lead to cells not functioning properly, but also not dying as they should and instead remaining in a zombie-like state. It is thought that these damaged cells, known as senescent cells, enter this state as a way of not becoming cancerous, but this also has a downside. The senescent cells can accumulate in various tissues and organs, and they are not just passive clutter—they secrete pro-inflammatory molecules such as cytokines, chemokines, growth factors, and proteases.
The phenomenon is known as the senescence-associated secretory phenotype (SASP) and leads to an inflammatory environment that can result in chronic tissue damage and contributes to a range of diseases (Fig. 1), including liver and lung fibrosis, atherosclerosis, diabetes, and osteoarthritis3. Consequently, these cells have become a target for the development of anti-aging therapeutics. Among the companies exploring this approach, some are developing senolytic drugs that directly target senescent cells, while others are manipulating mechanisms that modulate senescent cells.
One of the longest-established companies, Unity Biotechnology, was founded in San Francisco in the United States (US) in 2011 by academic leaders in the field including Jan van Deursen at the Mayo Clinic, US, and Judith Campisi at the Buck Institute for Research on Aging, Novato, California, US, and is backed by high-profile investors such as Jeff Bezos and Peter Thiel (Table 1). The company is focused on developing small-molecule drugs that clear senescent cells in diseased tissues, achieving this by targeting pathways involved in apoptotic cell death that have also been pursued to kill cancer cells.
Unity’s original lead candidate, UBX0101, was a small-molecule inhibitor of MDM2 designed to boost the activity of the pro-apoptotic protein p53. However, its development was abandoned in 2020, when it failed to surpass a placebo in reducing joint pain and stiffness in a phase 2 trial involving patients with osteoarthritis of the knee. The results cast a pall over the senolytics field, but with researchers noting various potential reasons for failure including a sub-optimal biological target, a compound with weak senolytic activity and a high placebo response2, the company has regrouped and persisted.
Unity is now developing UBX1325, a potent small-molecule inhibitor of the anti-apoptotic protein BCL-XL, on which senescent cells rely to survive. Unity accessed the compound through a collaboration established in 2016 with the China-based biopharma company Ascentage Pharma, and it is currently in phase 2 trials for the treatment of age-related diseases of the eye. In April 2023, Unity announced positive top-line results from a phase 2 study of UBX1325 in patients with diabetic macular edema, showing improvements in visual acuity over 48 weeks following a single intravitreal injection of the compound.
Another senolytic approach that has reached clinical trials is treatment with the combination of dasatinib, an approved anticancer drug that targets multiple kinases, and quercetin, a flavonoid that is found in fruit skin. The ‘D+Q’ combination has been shown to selectively clear senescent cells in animal models and humans, and a phase 2 trial known as SToMP-AD to assess the combination in patients with mild cognitive impairment or early-stage Alzheimer’s disease was started in 2021. A phase 1 trial supporting the combination’s safety and tolerability was published earlier this year4.
Company
Location
Therapeutics and platforms in development
Unity Biotechnology
- Raveena Bhambra
10 breakthroughs that could soon slow or reverse your biological age. The biggest killers in the modern world, like dementia and cancer, are down to ageing. Is it possible to tackle the ageing process so we can live for longer and stay healthier too? Andrew Steele. Published: May 25, 2024 at 9:14 am.
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Sep 3, 2020 · 1. Nostalgia is usually a yearning for our past selves, not just for a time and place. We crave to feel the positive emotions that we felt, to connect to the version of ourselves we were at the...
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