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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

  • +

    Whats the good news ?

  • +Anti-aging vs. increasing longevity: whats 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 Alzheimers

    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