Today's review paper is a look at views on aging on the other side of the world, a counterpoint to commentaries from US and European sources. It is interesting to compare the intersection between science and policy in different regions of the world, when it comes to perspectives on degenerative aging, the enormous costs of age-related disease, and what is to be done about it. It is only comparatively recently that scientific advances have offered the potential for aging to become anything other than an inevitable, enormous cost to be suffered. Governments with entrenched and growing entitlement programs (such as the US Social Security) or command and control health systems (such as the UK NHS) - both transfers of wealth to the old - face insolvency and collapse as the fraction of the population that is old and expecting not to work expands over time.
Regardless of entitlement programs, everyone in every country faces a future of personal decline, pain, loss, and death. While much of the literature is focused on funding and the collapse of government programs, the real reason to make progress is this point about individual suffering. A world in which people did not decline with age would be a world in which people can support themselves through multiple careers and a life worth living. It is a goal to aim for, step by step, via the development of new medical technologies.
Still, few government bodies have waded in to talk in earnest about funding research to prevent and reverse degenerative aging. Where discussion takes place, it is largely focused on approaches such as calorie restriction mimetic drugs, unlikely to do much more than very modestly slow aging in humans. Policy is stuck in the era of aging as a costly inevitability, and the cause of a future collapse due to unsustainable entitlements. There is always considerable lag between an expansion of the bounds of the possible, driven by new technology, and policy white papers, of course. But still, the first rejuvenation therapies exist, in the form of first generation senolytic drugs, and it won't be too many years before their use becomes widespread. The world at large has a great deal of catching up to do in present thinking on the future of aging and its treatment.
One of the key issues facing public healthcare is the global trend of an increasingly ageing society which continues to present policy makers and caregivers with formidable healthcare and socio-economic challenges. Ageing is the primary contributor to a broad spectrum of chronic disorders all associated with a lower quality of life in the elderly. In 2019, the Chinese population constituted 18% of the world population, with 164.5 million Chinese citizens aged 65 and above (65+), and 26 million aged 80 or above (80+). China has become an ageing society, and as it continues to age it will continue to exacerbate the burden borne by current family and public healthcare systems.
Europe is characterized by three types of care provision: 1) 'crowding out', whereby the state largely replaces family care; 2) 'crowding in', whereby the state promotes family care; 3) 'mixed responsibility', whereby both the state and the family take a joint responsibility for care, yet have separate functions. In China, family is still the traditional provider for elderly care. In order to deal with the ongoing boom in the elderly population, the Chinese government has put more effort into funding research on ageing and its related diseases in recent decades. More attention has been placed on the development of pharmacological strategies against ageing, organ degeneration and major ageing-related diseases.
Targeting classic longevity pathways
Calorie restriction (CR) was first demonstrated as an effective way to extend lifespan in rodents, however the physiological mechanisms behind its anti-ageing effectiveness were not fully understood at the time, and remain uncertain. Later studies have suggested that CR might extend lifespan by regulating insulin-like growth factor (IGF) and mammalian target of rapamycin (mTOR) pathways. Metformin is primarily known for treating type 2 diabetes, with its underlying molecular mechanisms leading to the to down-regulation of IGF-1 signaling, and the inhibition of cellular proliferation, mitochondrial biogenesis, reactive oxygen species (ROS) production, DNA damage, activity of the mTOR pathway, etc. Acarbose has been shown to partially mimic the effects of CR and extend lifespan in mice by controlling blood sugar and slowing carbohydrate digestion. Rapamycin, a well-known inhibitor of mTOR, has shown life-extending effects in all model organisms and postpones the onset of age-associated diseases.
Nicotinamide adenine dinucleotide (NAD+) is a fundamental molecule in human life and health; while there is an age-dependent reduction of NAD+, NAD+ augmentation extends lifespan and improves healthspan in different animal models as well as shows potential to treat different neurodegenerative diseases based on phase I clinical trials. NAD+ precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) have emerged as promising approaches for intervention against ageing phenotypes and age-related diseases. Supplementation via these precursors can elevate NAD+ level in vivo and improve glucose metabolism, mitochondria biogenesis, DNA repair, neovascularization, and neuroprotection.
Senescent cells accumulate in aged tissues and this accumulation is considered one of the driving forces of ageing. Senolytics are a class of molecules specifically designed to induce apoptosis of these senescent cells. Clearing senescent cells in mice has been shown to substantially alleviate ageing phenotypes, producing potent therapeutic effects in ageing-related diseases such as Alzheimer's disease, atherosclerosis, and osteoarthritis. The senolytic cocktail of dasatinib plus quercetin (DQ) decreased naturally occurring senescent cells, improved mobility, and reduced the risk of mortality. While clinical trials on senolytic drugs are mainly conducted in the USA, the concept of reducing senescent cells to delay the ageing progress has attracted interest from all over the world. Since 2016, the National Natural Science Foundation of China (NSFC) has set up special programs, providing millions to support research on cellular senescence and organ degeneration.