Abstract Objections to life extension often focus on its effects for individual well-being. Prominent amongst these concerns is the possibility that life extending technologies will extend lifespan without preventing the ageing of the mind. Writers on the subject express the fear that life extending drugs will keep us physically youthful whilst our minds decay, succumbing to dementia, boredom, and loneliness. Generally these fears remain speculative, in part due to the absence of genuine life extending technologies. In this paper, however, I (...) examine the implications of an existing life extension technology. Caloric restriction (CR) and drugs that mimic its effects, such as rapamycin, metformin and resveratrol have been shown to increase average and maximum lifespan in a wide variety of organisms, and seem likely to do so in humans. Moreover, some CR mimetic drugs (CRMs) are already widely used. This means that they present a pressing test case for fears about mental ageing in an extended life. Misgivings about mental ageing can be divided into biomedical factors such as the likelihood of brain ageing, and psychological factors such as loss of meaning and boredom. I argue that studies of CR suggest that brain ageing will be beneficially slowed. However, it is less clear that deleterious aspects of psychological ageing can be similarly retarded. I argue that this reduces the desirability of life extension unless major social changes can be made. (shrink)

Rationale, aims and objectives To compare the pharmacotherapeutic approaches to diabetic hypertension of family physicians (FPs) and general practitioners (GPs). Methods A retrospective prescription-based study was conducted in 15 out of a total of 20 health centres, involving 115 primary care physicians – 77 FPs and 38 GPs, representing 74% of the primary care physicians of Bahrain. Prescriptions were collected during May and June 2000 to comprise a study population of 1266 diabetic-hypertensive patients. Results As monotherapy, angiotensin-converting enzyme (ACE) inhibitors (...) (37.9%) and β-blockers (38.3%) were the most commonly prescribed classes of antihypertensives by FPs and GPs, respectively. Calcium channel blockers (CCBs) were ranked third by both categories of physicians. For two-drug combinations, a β-blocker and an ACE inhibitor was the combination of choice for both physician categories. Patients managed by the FPs were more likely to receive a β-blocker–CCB combination (17.4 vs. 14.9%) or a diuretic–ACE inhibitor combination (16.7 vs. 11.4%) and less likely to receive a β-blocker–diuretic combination (11.8 vs. 16.7%) than those managed by the GPs. The proportion of patients receiving antihypertensive combinations was 40.6 and 38.5% for FPs and GPs, respectively. While the GPs prescribed CCB as a monotherapy to the elderly most often, the FPs choice was a β-blocker. Diuretics were less preferred by both FPs and GPs. β-Blocker–ACE inhibitor was again the most preferred combination of both FPs and GPs. FPs prescribed CCB–β-blocker combinations more often than GPs (P = 0.01), whereas CCB–ACE inhibitor combinations were less preferred (P = 0.09). A trend towards excessive use of short-acting nifedipine as monotherapy for elderly patients, both by FPs and by GPs, was noticed. Glibenclamide, alone or in combination with metformin, was the foremost antidiabetic drug prescribed by FPs and GPs. Middle-aged (45–64 years) patients seen by GPs were more likely to receive glibenclamide than those treated by FPs (P = 0.001) and less likely to receive gliclazide (P = 0.01). Combinations of a β-blocker with either glibenclamide or insulin were prescribed considerably more often by GPs.Conclusions Within the same practice setting, a substantial difference was observed between FPs and GPs in terms of preference for different classes of drugs in the management of diabetic hypertension. The compliance of both FPs and GPs was suboptimal; overall, the compliance of the FPs was closer to the recommended guidelines, however. Educational programmes should specifically address these inadequacies in order to improve the quality of health care. (shrink)

After retirement, older people often find themselves far from their children and grandchildren, and many spend their last years isolated and alone. As traditional concepts of family and social institutions fragment, social networks weaken, leading to an epidemic of loneliness, and substance abuse and suicide in developed countries. In fact, life expectancy in the US has dropped for the past few years, in large part due to a dramatic increase in suicide and drug overdose. None of these social problems is (...) likely to be solved by metformin. They point to a crisis of identity and meaning, an existential crisis. In this context, one might wonder if we are already seeing the effects of tinkering with our lifespan. There are many more conclusions one could draw about the implications of longevity, many of which have been elegantly described in Beyond Therapy: Biotechnology and the Pursuit of Happiness, published by the President’s Council on Bioethics, which I used as a reference for this talk. I hope I have been successful in providing a 10,000-foot view of the questions of efforts to extend human longevity and its implications that will provoke thought and discussion. I would like to end these reflections by turning back to my favorite transhumans. The reason we love superheroes is not for their superior strength or intelligence, but their characters. They use their powers to protect and serve humanity rather than dominate or annihilate it. It is not their gadgetry that makes them great, but how they use it to save the vulnerable. Even as a small child I knew that if everyone acted the way they did, the world would be a better place. The moral of every story was that the “enhancement” humanity needed would not come as the fruit of technology, but of virtue. (shrink)

An abundance of data unequivocally shows that exercise can be an effective tool in the fight against obesity and its associated co-morbidities. Indeed, physical activity can be more effective than widely-used pharmaceutical interventions. Whilst metformin reduces the incidence of diabetes by 31% (as compared with a placebo) in both men and women across different racial and ethnic groups, lifestyle intervention (including exercise) reduces the incidence by 58%. In this context, it is notable that a group of prominent medics and (...) exercise scientists recently sent a well-publicised letter to the General Medical Council and Medical Schools Council calling for the introduction of evidence-based lifestyle education into all medical curricula. The letter warns that there is a lack of understanding of the impact that exercise and nutrition can have on physical health amongst doctors. In the absence of an educational overhaul, the signatories warn that the government is likely to fail to reach its goal of preventing tens of thousands of premature deaths from heart disease and cancer by 2020. Whilst we agree with the need to address this apparent lack of understanding, we argue that the ethical justification of doing so is not limited to this broadly beneficence-based justification. There is also a justification grounded in the duty of non-maleficence, that is, the duty to avoid unreasonably harming patients. This duty requires that doctors refrain from (i) preventing patients from undergoing beneficial treatment without good reason, (ii) exposing patients to unreasonable risks and (iii) reducing the therapeutic effect of an effective medical intervention. This requires an understanding of the physical impact of exercise. (shrink)

AMP‐activated protein kinase (AMPK) is an evolutionarily conserved cellular switch that activates catabolic pathways and turns off anabolic processes. In this way, AMPK activation can restore the perturbation of cellular energy levels. In physiological situations, AMPK senses energy deficiency (in the form of an increased AMP/ATP ratio), but it is also activated by metabolic insults, such as glucose or oxygen deprivation. Metformin, one of the most widely prescribed anti‐diabetic drugs, exerts its actions by AMPK activation. However, while the functions (...) of AMPK as a metabolic regulator are fairly well understood, its actions in neuronal cells only recently gained attention. This review will discuss newly emerged functions of AMPK in neuroprotection and neurodegeneration. Additionally, recent views on the role of AMPK in autophagy, an important catabolic process that is also involved in neurodegeneration and cancer, will be highlighted. (shrink)