Some Talks by Scholars in IAG 2005

1
Some Talks by Scholars in IAG 2005

• Reported by Claudia K Y Lai, RN, PhD

2
Topics

• Osteoporosis
• Frailty
• Caloric Restriction Longevity
• Psychosocial Theory (SOC) in Aging
• Longitudinal Studies

3
Osteoporosis (Hajime Orimo, Japan Jun 28, 2005)

• Risk of arthrosclerosis with Ca
• Parathyroid hormone increase in advancing age
• Factors involved in pathogenesis osteoporosis and
  arthrosclerosis
• Vitamin K (important in producing Ca binding
  proteins)
• Cytokines
• Oxidized LDL
• Matrix Glaprotein Gamma-carboxyglutamate (may
  be protective of protein from calcification)

4
Bone Turnover

• Osteocalcin is a vitamin-dependent protein
  produced by osteoclast
• Bone strength significantly decreased in mouse
  without osteocalcin
• Vitamin K2 regulation of bone homeostatis versus
  mediated by the steroid xenobiotic receptor (SXR)

5
Vitamin Intake Fracture

• Higher consumption of Natto (fermented beans)
  decreased fracture of hip
• Japan Natto contains tremendous amount of K2
• K2 only found in Natto, not in other types of
  food
• USA increase intake of vit K1 correlated with
  lower incidence of hip
• 2 years administration of vitamin K decrease
  significantly vertebral
• Rotterdam study vit K reduces the risk of
  coronary heart disease especially vit K2
• Vit K2 has an anti-aging effect

6
Osteoporosis Assessment

• Current (2002) International Osteoporosis
  Foundation (IOF) Guidelines
• History, bone mineral density (BMD) with risk
  factors
• Proposed
• risk for given BMD levels varies according to
  age and other risk factors
• Cases with T scores gt -2.5 are at risk for hip
• NORA study 52 of women with osteoporotic had
  peripheral T scores between -1 - 2.5 (Siris et
  al., 2004)

7
WHO Risk Assessment Tool

• 2004 WHO Assessment Recommendations
• Age
• BMD
• Smoking
• Ever use cortisol
• Alcohol
• Parental history

8
2003 National Osteoporosis Foundation (NOF)
Guidelines

• In absence of risk factors, start therapy to
  reduce risk in female with BMD T-scores below
  -2.0 by DXA (Dual energy X-ray Absorptiometry) of
  the hip or spine.
• With one or more risk factors, treatment for
  people below -1.5 DXA of the hip or spine.

9
Whom to treat?

• WHO is developing an algorithm that will combine
  BMD T-scores data at the hip with other key
  clinical risk factors to assess probability
  over a 10-year period
• Treatment determine by available resources,
  societal values, etc.

10
Which treatment is best?

• HRT (Hormonal Replacement Therapy) initial after
  menopause
• Raloxifene (A selective estrogen receptor
  modulator)
• Bisphosphonates bone specific
• Parathyroid Hormone (PTH)
• Calcium
• Vitamin D3
• Vitamin K2

11
Use of Estrogen

• Uses
• Side-effects
• Women Health Initiative study
• Increase risk of Coronary Heart Disease
• Increase stroke
• Increase breast cancer
• Increase PE
• Decrease risk of colon cancer

12
5 Ways to Prevent Osteoporosis

• Maintain a Calcium-rich diet
• Get plenty of Vitamin D
• Engage in weight bearing exercise
• Limit your drink and dont smoke
• Consider HRT or other types of medication

13
Frailty frail older adults are vulnerable and at
high risk for a range of adverse health outcomes.

• Prevalence of phenotype of frailty
• overall 7, increase with age.

The physical or functional characteristics of an
organism, produced by the interaction of genotype
and environment during growth and development.
Symposium chaired by Paul H. M. Chawes Jun 30,
2005
14
Overarching hypotheses

• Clinical syndrome associated with aging
• Manifested along a continuum of multisystem
  dysregulation
• Concepts and import of frailty clinical syndrome
  may be clues to ultimate cause

15
Geriatricians Perspective

• Age-related state of vulnerability
• Considered as recognizable clinically
• Stated to occur in 40 of persons gt 80 years
• High risk for mortality falls, disability,
  hospitalization

16
A Spectrum of the Frailty Concept
17
Clinical Manifestation

• Sarcopenia
• Weight lost
• Decrease strength and decrease exercise tolerance
• Decrease balance
• Low physical activity
• Cognitive vulnerability
• Slow motor processing
• Response to stress

18
Established Principal Associations

• Weight loss (muscle mass loss) gt weaken, lowered
  exercise tolerance gt weakness gt slowed walking
  speed gt decreased activity gt low intake
  (mismatch) gt clinical under-nutrition (a vicious
  cycle)

19
Operationalized Theory of Cycle into a Phenotype

• gt 3 criteria present equals to frail
• Weak
• Low energy/exhaustion
• Slow walking speed
• Low activity
• Weight loss
• Aggregate phenotype predicted mobility disability
  better than individual criterion
• Increase risk of mortality

20
Questions

• If frailty is a syndrome, how does it develops?
• Is deregulation a function of genetics, molecular
  and functional systems?
• Interconnections of systems
• Multisystem alterations may underlie loss of
  reserve

21
Challenge Ahead

• Geriatric medicine is becoming more difficult to
  become the central role because
• Integration into acute care
• Shorter length of stay (LOS)
• LTC services
• Presently LOS aimed at 6 days regardless of age

22
Caloric Restrictions and Human Lifespan
23
Calorie Restriction

• Long advocated by UCLA School of Medicine
  professor Roy Walford.
• This concept suggests that by reducing calories
  by 10 or more human life span can be
  substantially increased.
• Various groups around the US actually practice
  this concept called CRAN (Calorie Restriction
  with Adequate Nutrition).

24

• CRAN has been shown to dramatically extend the
  lives of laboratory animals. Rats, mice and
  hamsters experience significant life span
  extension from a diet containing 35 of the
  calories, but all of the required nutrients.
• Mean life span was increased 65 and maximum life
  span was increased by 50 when CRAN is begun just
  before puberty.
• The exact mechanism by which caloric restriction
  has such dramatic effects is still
  unknown.http//www.benbest.com/calories/calories.
  htmlhttp//www.walford.com/bio.htm

25
Conclusion from one speaker

• Caloric restriction exhibits its effect through
  the reduced GH-IGF-1 axis although caloric
  restriction may have other mechanism affecting
  aging and longevity

26
Caloric Restriction another speaker

• Cortisol level decreased in CR affecting lifespan

27
Protein turnover and its effects

• Protein turnover synthesis and degradation
• General consensus protein synthesis decrease
  with age
• CR modulates some effects of aging
• Age and CR modify proteasome structure and
  function, its effects are now still unclear.

28
General effects of food restrictions on rodents
(1)

• Increase LE and maximum lifespan
• Retards a spectrum of age changes physiologic
  systems
• Retards the progression or prevent the occurrence
  of age associated disorders

29
General effects (2)

• Currently testing the involvement of physical
  activity and plasma glucose in mechanisms of
  aging
• IGF levels very low in CR rats
• In CR rats gt cortisol levels high, but stress
  resilient
• Effects of CR in terms of voluntary activity were
  shown to be tremendous
• BW dramatically lowered

30
The Question

• Is one or more of the metabolic differences a key
  factor in CR, and therefore in aging?

31
Effect of CR (3rd Speaker)

• CR produces a new animal with new mechanism
• For entire lifespan the CR animal has a lower
  level of plasma glucose
• Diabetics age faster, may be glucose interest in
  amino acid, DNA
• Plasma glucose not affecting mortality

32
Conclusion

• Lower plasma glucose is not as important factor
  in the action of dietary restriction on aging
• Data suggest that decrease plasma glucose does
  not necessary ..?

33
Selective Optimization Compensation a
Psychology Theory of Aging

• Lecture notes from Paul Baltes, Jun 29, 2005 at
  the World Congress of Gerontology

34
SOC related psychological model of proactive aging

• 3 General Functional Perspectives
• Lifespan psychology
• Bicultural co-construction
• Successful (adaptive aging)

35
Summary of propositions of lifespan psychology

• Developmental
• Diversity/variation
• Development as gain and loss
• Plasticity/constraints
• Shifting balance (with increasing age, more
  difficult to balance)
• Proactive aging

36
Age and Memory

• Working memory decrease at a rate of 1 per year
  starting from age 40

37
Large variability and plasticity across ages

• E.g., age world record in marathon is held by an
  individual aged 70 at 3 hours
• Questions re plasticity
• How much plasticity is left in aging?
• How much can we use it after we are born?
• Intraindividual variability becomes larger with
  aging

38
Why use SOC?

• To develop general and specific resources
• To allocate resources
• if you choose the right half, the half will be
  more than the whole.
• Words of wisdom from Hesiod

39
Longitudinal Studies

• Symposium chaired by Torbjorn Svensson Jun 29,
  2005

40
Lund Study 1988

• Gothenburg QOL instrument 30 items and 7 domains
• Active coping is indeed a protective mechanism,
  although not prolonging life but maintains well
  being
• It is just as bad to report symptoms as to have
  diagnosed diseases.

41
LASA 1992 (Longitudinal Aging Study Amsterdam)

• Summary Time sequential analysis
• From 1992 to 2002 count frequency and support
  exchanges
• Conclusion both parents and child spent less
  time to interactions and exchange

42
GAS (Good Aging in Skane)

• A substudy of SNAC Swedish National Study on
  Aging and Care)
• A newly established longitudinal study
• Health and health care consumption do not
  necessarily work in the same direction
• Only 10-15 of those reaching age 65 have
  functional disability and needs help from others
• Conclusion informal care is important in
  caregiving
• May be more costly for in-home care because more
  specialist visits etc.

43
CLSA (Canadian Longitudinal Study on Aging)

• Protocol development website
• www.fhs.mcmaster.ca/clsa

44
What do we have in Hong Kong?