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Anti-aging advances

Michael Chee Duke-NUS Graduate Medical School

+Aging: The bad news

  With the possible exception of

caloric restriction* nothing else has been conclusively shown to slow the aging process

* clear evidence in some animals but human data is conflicting

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What’s the good news ?

+Anti-aging vs. increasing longevity: what’s the difference

  Aging refers to biological changes at the cellular level

  Longevity can be achieved by dodging things that would otherwise kill you

+Dodging what?

  Major problems associated with increased age   Heart attacks   Stroke   Cancer(s)   Neurodegenerative disease   Complications of Diabetes Mellitus   Degenerative joint disease   Osteoporosis   Cognitive decline / loss of musculo-skeletal

integrity

+Finding the fountain of youth

+There is no free lunch…

+Finding solid evidence is a slow process

  Listen to old men (and women)

  Test animals   Is the animal model relevant to humans   How long will it take to generate data?

  Sift through lots of research data

+Resveratrol: new life from old grape skins?

  From red grape skins

  Very high quantity required

  Activator of Sir2

  Mimics Caloric Restriction

+Caloric restriction

  The ONLY method known to influence aging and increase longevity

  May act through epigenetic pathways related to the developmental theory of aging

  Relationship with IGF-1?

+Dietary supplements

  Operate on the assumption that more of a good thing is better

  Seek to boost intake of substances that are found in foods

  Provide these substances in purified form

  Clinical trials that evaluate the usefulness of supplements evaluate a particular dose range

+Vitamin supplements to prevent cancer

+Vitamin supplements to prevent cancer

  Vit E + selenium reduce gastric cancer (Chinese Cancer Prevention Study 1993)

  Beta-carotene supplementation may increases the risk of lung cancer (CARET 1994)

  Vit E + Selenium supplementation do not reduce the risk of prostate cancer (SELECT 2008)

  Vit D may be useful in reducing risk of breast and colorectal cancer (2008 metanalysis)

  Vitamins A, D + E supplementation do not appear to reduce the risk of cancer (2009 metanalysis)

  ? Benefit of Vit C

+Anti-oxidants …1

  Normal cellular processes result in generation of ROI

  ROI – Reactive oxygen intermediates

  These damage cellular structures

  Normally there is damage control

  Damage control weakens with age

+Anti-oxidants …2

  Vitamins A, C & E, Co-enzyme Q10

  Resveratrol

+Genes and cancer risk

  Early days; most of 240 published associations only a handful were reliable

  BRCA1, BRCA2, PARP1: Breast cancer

  XRCC1 & ERCC 2: Lung cancer

  CCND1: Head and neck cancer

+Gingko and memory

  Does not reverse Alzheimer’s

  Does not have short term benefits of improving cognition in healthy persons

+Genes and aging

  Many candidates: see

http://genomics.senescence.info/genes/clues.html

  Latest candidate is FOX03A

  Environment influences gene expression: your fate my be determined but you can still make a difference