Ethical perspectives on advances in biogerontology

摘要

Worldwide populations are aging with economic development as a result of public health initiatives and advances in therapeutic discoveries. Since 1850, life expectancy has advanced by 1 year for every four.1 Accompanying this change is the rapid development of anti-aging science. There are three schools of thought in the field of aging science. One perspective is the life course approach, which considers that aging is a good and natural process to be embraced as a necessary and positive aspect of life, where the aim is to improve the quality of existing lifespan and “compress” morbidity. Another view is that aging is undesirable, and that rejuvenation and indeed immortality are possible since the biological basis of aging is understood, and therefore, strategies are possible for engineering negligible senescence. Finally, a hybrid approach is that life span can be extended by anti-aging medicines but with uncertain effects on health. While these advances offer much promise, the ethical perspectives are seldom discussed in cross-disciplinary settings. This article discusses some of the key ethical issues arising from recent advances in biogerontology. The biological basis of aging is increasingly understood, and myriad ways of altering aging are now known. One cause of aging is the accumulation of molecular damage, such as DNA mutations and misfolded proteins. Damage can further lead to “meta-effects,” such as the emergence of senescent cells or dysfunctional mitochondria, which contribute to a feedback loop of damage and dysfunction.2 These deleterious causes of aging are offset by endogenous repair and rejuvenation pathways, many of which are linked to nutrition and metabolism. Dozens of genetic, pharmacological, and other interventions can slow aging in the laboratory, in species ranging from yeast to non-human primates. Two major classes of interventions are currently entering human clinical trials. One class activates nutrient signaling pathways to turn on endogenous repair and rejuvenation pathways. The other class targets deleterious meta-effects of aging, such as senescent cells or stem cell dysfunction. Metformin is a diabetes drug that appears to activate aging-related nutrient signaling pathways.3 A large randomized controlled trial to test if metformin can delay age-related multimorbidity is being planned in the United States. Inhibitors of the protein-sensing TOR complex can activate protein repair pathways and extend lifespan in the laboratory,4 and a clinical trial recently showed that TOR inhibitors can prevent respiratory infections in vulnerable elderly patients.5 Drugs that restore the metabolic signaling molecule NAD6 and activate NAD-dependent sirtuin enzymes are also under investigation.7, 8 Eliminating senescent cells extends healthy lifespan in the laboratory by reducing damaging inflammation,9, 10 and a number of drugs to target senescent cells are entering clinical trials.11 Stem cells can be rejuvenated in the laboratory with factors derived from young blood,12 or by direct infusion of healthy stem cells. Both approaches are now being studied in clinical trials to treat physical frailty13 and dementia.14 In the future, direct genome editing could be used to treat aging.15 An international consortium is working to move anti-aging therapies more rapidly into clinical trials.16 If maintenance of function rather than life extension is a key desirable outcome during the aging process, then technology has an important role in achieving this goal in the presence of physical disabilities as well as cognitive function impairments. Stroke is a commonly encountered disease that increases with age and is a major contributor to disability burden. Advances in technology-assisted rehabilitation are developing rapidly in augmenting neuroplasticity during the recovery period through the use of exoskeleton robotics. Robotics are also being used for surgical procedures to improve accuracy, and to a smaller extent, servi