Anti-ageing: hope or hype Centre on Ageing Spring Symposium 2009 Patrick Montgomery The dream of eternal youth • One of mankind’s oldest quests • Recurring promise of charlatans and scam artists throughout the ages • Slowing or reversing ageing is not the same as treating or preventing disease; both can extend longevity but in different ways Moral, Ethical and Societal Implications of Increased Longevity • Average lifespan has increased 3-4 fold over the past 200 years • Average lifespan continues to increase by 0.25 years for every calendar year with no sign of stopping • Scientific and medical interventions into the aging process is a reality Moral, Ethical and Societal Implications of Increased Longevity Objections have been raised about the wisdom of extending the lifespan: – World is already over-populated – Keeping resources for the senior population – Extending the phase of dependency – Redefining the meaning of being human Is there any scientific validity to claims that we can slow ageing? • Depends upon an understanding of the fundamental causes of the ageing process • There has been an explosion of knowlegde in this area… • But no definite proof as to the cause of ageing or a therapy for this Telomeric Biology • Telomeres are down-regulated in most tissues from 20th week embryonic life, but can be induced • Telomerase knock-out mice eventually develop senescent changes (after multiple generations) • Clinical syndrome “dyskeratosis congenita” due to telomerase deficency Telomeric Biology • Some evidence that telomeres may shorten with chronic stress (caregivers of children with disabilities) or elderly caregivers • Telomeres may lengthen again if stress is relieved • Mechanism of shortening may be through cytokines, stress hormones or oxidative stress Telomerase-based therapeutics • Sponsored by Geron Corp • Screened many natural products for substances which activate telomerase • Found 2 candidates – TAT1 and TAT2 • Being developed as both topical and systemic drugs to counter aging • Telomerase inhibitor in phase 1 and 2 trials Roy Walford – proponent of caloric restriction for life extension Nature Nov 2006: Resveratrol improves health and survival of mice on a high-calorie diet • Resveratrol (3,5,4'-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. • In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction Gerontologic “party line” • "position paper" on aging research, titled "The Truth about Human Aging", which appeared in Scientific American in May of 2002, • Olshansky, Perls and others wrote that while some hormones appear to ameliorate certain problems associated with aging in some studies, none "has been proved to slow, stop or reverse aging” S. Jay Olshansky • Michigan State University, Lansing B.S. 1975 Psychology • University of Chicago M.A. 1982 Sociology • University of Chicago Ph.D. 1984 Sociology Tom Perls • Internal Medicine (residency: Harbor UCLA Medical Center) and Geriatrics (fellowships: Harvard Medical School and Mount Royal Hospital in Melbourne Australia). He earned his MPH at the Harvard School School of Public Health GERONTOLOGICAL BIAS: • "Past and anticipated advances in [aging] interventions only influence the manifestations of aging--not aging itself. The biomedical knowledge required to modify the processes of aging that lead to age-associated pathologies confronted by geriatricians does not currently exist." GERONTOLOGICAL BIAS: • "Eliminating all aging-related causes of death currently written on the death certificates of the elderly will not increase human life expectancy by more than 15 years." GERONTOLOGICAL BIAS: • "No product currently sold has been demonstrated to reverse aging. No hormone, has been proved to slow, stop or reverse aging. Growing younger is a phenomenon that is currently not possible." GERONTOLOGICAL BIAS: • "Optimum lifestyles, including exercise and a balanced diet along with other proven methods for maintaining good health, contribute to increases in life expectancy by delaying or preventing the occurrence of age-related diseases. Osteopaths ask for $120 million after being criticized; experts question limits of scientific debate • The plaintiffs in the lawsuit are Ronald Klatz and Robert Goldman, a pair of osteopaths who founded the A4M • The doctors, who also earned MD degrees in Belize, argue that their critics have defamed them as scientists and interfered with their business relationships American Association for Anti- Aging Medicine (A4M) • An association which un-abashedly promotes the possibility of interventions into the aging process • Convention in Las Vegas this month • Has been publicly opposed by conventional gerontologists, one of whom has given the group the “silver fleece award” World Record 321 Consecutive Handstand Pushups Dr. Aubrey David Nicholas Jasper de Grey, Ph.D. • He is the author of the Mitochondrial Free Radical Theory of Aging. He is now working to develop a tissue-repair strategy, that would, in effect, rejuvenate the human body and allow indefinite lifespan -- a medical goal he refers to as engineered negligible senescence. A4M’s view of aging The Gerontological Society’s view of aging GRECC 30th Anniversary symposium: Understanding Frailty: pathophysiology, prevention and treatment Mulligan et al Gainesville Florida GRECC Pathophysiology of frailty • Extensive discussion of hormonal basis of sarcopenia • Noted an NIH moratorium on studies of testosterone replacement because of disappointing initial results and concern over side-effects Preventing falls in the frail • Physiotherapist presented case • Male in 80’s with daily falls • Severe postural hypotension, severe hypoglycemia from over treatment • 4 days in hospital before he could begin rehab – stayed in GEM unit for 2 weeks • Discharged mobile but no stronger Preventing falls in the frailty • Testosterone patch placed on the patient at discharge, also given exercise program • No direct follow-up as he was from out-of – state, but has gained strength and had no falls • They ascribe improvement to the effects of the testosterone patch!!! Does the debate over lifespan extension have application to clinical geriatrics? • Difference between hope and false hope • Tension between delivering enhancement or replacement strategies and coping or accepting strategies • Some recent advances in geriatric medicine conform to this paradigm: e.g. Cholinesterase inhibitors vs Family Therapy for AD Does the debate over lifespan extension have application to clinical geriatrics? • Stigma attached to the aging process could be removed if real change was thought possible • Enthusiastic embracement of interventional technology could make geriatrics more attractive to trainees and patients/clients alike Does the debate over lifespan extension have application to clinical geriatrics? • Lifespan extension technology will likely be the domain of specific medical specialties – brain aging will be dealt with by neurology, endocrine with deal with bone aging etc. • Geriatric medicine is left with the “palliative” aspects of aging: i.e. coping and accepting what medicine and science can’t fix Conclusions • Both professionals and clients/patients want to believe that there is a technological answer to aging or associated disease processes – they continue to promote interventions despite little or no data • The difference between A4M and conventional medicine is not as great as one might think Conclusions • Geriatric medicine and gerontology likely do present a balanced view of aging, but this balance does not make it popular • Hope versus false hope versus “is there any hope” .