Oldest American - 114 - Dies

[Guest guest]

Hi folks:

http://www.foxnews.com/story/0,2933,140374,00.html

Rodney.

[Guest guest]

Hi All,

Centenarian offspring death causes are presented in this latest

Perls pearl

on centenarians. The odds ratio of the childhood death was 1.74 for

the offspring,

since: " 30% of the deaths of centenarians' offspring occurred from

childhood

illnesses, compared with 8% of controls " , leading to: " Mean age at

death was

40.7 for centenarians' offspring and 56.5 for controls " .

At older ages, the offspring die of cancer at the same rates as

controls?

See the second discussion paragraoh.

The pdf is available and and excerpts of the paper are below.

J Am Geriatr Soc. 2004 Dec;52(12):2074-6.

Lower all-cause, cardiovascular, and cancer mortality in

centenarians'

offspring.

Terry DF, Wilcox MA, McCormick MA, Pennington JY,

Schoenhofen EA, Andersen SL, Perls TT.

... Cross-sectional study. Setting: Community-based, nationwide

sample. Participants: Family pedigree information was collected on

295 offspring

of centenarians (from 106 families with a parent already enrolled in

the

nationwide New England Centenarian Study) and on 276 controls (from

82 control

families) from 1997 to 2000. Controls were individuals whose parents

were born

in the same year as the centenarians but at least one of whom died at

the

average life expectancy. ...

Centenarians' offspring had a 62% lower risk of all-cause mortality

(P<.001), a

71% lower risk of cancer-specific mortality (P=.002), and an 85%

lower risk of

coronary heart disease-specific mortality (P<.001). Significant

differences were

not found for other causes of death. However of those who died

centenarian

offsprings dead at a significantly younger age than controls.

Conclusion: These

findings suggest that centenarians' offspring have lower all-cause

mortality

rates and cause-specific mortality rates for cancer and coronary

heart disease.

These results suggest that mechanisms for survival to exceptional old

age may go

beyond the avoidance or delay of cardiovascular disease and also

include the

avoidance or delay of cancer. Moreover survival advantage of

centenarian

offsprings may not be due to factors related to childhood mortality.

Ultimately,

survival to exceptional old age may involve lower susceptibility to a

broad

range of age-related diseases, perhaps secondary to inhibition of

basic

mechanisms of aging.

PMID: 15571545 [PubMed - in process]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=15571545

... RESULTS

Based on family pedigree information, 27.5% of the con-trols

and 12.5% of the centenarians' offspring died in the

years before the study (P<0.001), resulting in a 62% lower

risk of all-cause mortality, as shown in Table 1. Centenar-ians'

offspring were found to have significantly lower can-cer-

specific mortality (P = .002) and coronary heart

disease–specific mortality (P<.001), resulting in a 71%

lower risk of cancer mortality and an 85% lower risk of

coronary heart disease mortality. No differences were found

between the two groups for other causes of death, including

aneurysm, childhood illnesses, stroke, neurological, acci-dental,

miscellaneous (liver disease, primary amyloidosis,

suicide, pulmonary fibrosis, and surgical complications),

and unknown.

Mean age at death was 40.7 for centenarians' offspring

and 56.5 for controls. Mean age at death, when childhood

deaths were excluded, was 61.6 for centenarians' offspring

and 60.0 for controls. Proportionately more controls died at

18 and older, as is shown in Figure 1 (Z score 5.01;

P<.001). Data on the age at death were unavailable for five

centenarians' offspring and six controls.

DISCUSSION

In spite of the small sample sizes for cause-specific deaths,

these findings suggest that centenarians' offspring have

lower all-cause mortality rates and cause-specific mortality

rates for cancer and coronary heart disease than controls.

The lower rates of coronary heart disease–specific mortality

are consistent with results of lower cardiovascular disease

and risk factor rates in living offspring of centenarians. In-

terestingly,

the difference in susceptibility for cardiovascu-lar

disease between the two groups diminishes over time,

with an 85% lower risk in those who died versus a 56%

lower risk reduction [ref. =] 1 in the survivors.

In contrast to prior research that demonstrated a sim-ilar

prevalence and age at onset for cancer in living offspring

of centenarians and controls,1,2 the current findings suggest

that centenarians' offspring have a 71% lower risk of dying

from cancer when compared with an age-matched controls.

It is possible that, at younger ages (e.g., <70), centenarians'

offspring have a lower risk of cancer than controls, but that

this difference disappears as the birth cohort ages. Left be-hind

are the survivors of the two groups, with similar sus-ceptibilities

to cancer.

The incidence of cancer in humans increases expo-nentially

with age.5 This may be a result of a steady accu-mulation

of mutations and an overall increase in the

mutation rate that occurs with aging.6 The individuals in

the cohorts who developed and died of cancer may have

been prone to multiple mutations at earlier ages, leaving

behind survivors who were less susceptible to cancer. Cen-tenarians'

offspring, more so than the controls, may have

inherited genetic variations from their long-lived parent

that protected them from multiple mutations, thus resulting

in lower cancer-specific mortality. For example, more than

130 human deoxyribonucleic acid repair genes have now

been described, many of them implicated in the modulation

of cancer and cellular aging.7

Although the overall mortality rate was lower for the

centenarians' offspring, it was found that, among those

who died, on average, the centenarians' offspring died at a

significantly younger age than the controls. Similar num-bers

of centenarians' offspring and controls died from

childhood illnesses (3.7% in centenarians' offspring and

2.2% in controls; P 5 .28), but as a proportion of total

deaths, 30% of the deaths of centenarians' offspring oc-curred

from childhood illnesses, compared with 8% of

controls, which accounts for the lower average age of death.

There are several demographic forces that could together or

individually cause a younger average age of mortality in the

centenarians' offspring who had died thus far. One possi-bility

is that the survival advantage of the centenarians'

offspring survivors is not due to an enhanced ability to sur-vive

factors related to childhood mortality but rather to

factors related to survival at substantially older ages. An-other

possibility is that the living offspring of centenarians

are a select cohort, who by virtue of surviving specific

childhood-related (and cohort-specific) illnesses, are more

likely than controls in the same birth cohort to survive to

much older age.

In addition to differences in the childhood deaths as a

proportion of all causes of death, centenarians' offspring and

controls had different proportions of other causes of death.

In the cases of cardiac and cancer deaths, these differences

were statistically significant despite the relatively small num-bers

of incident cases. It is anticipated that even larger sam-ples

would yield even more dramatic significance values for

deaths due to these diseases and would shed light on whether

differences exist for other diseases for which the incidence

was too low in both groups to make valid observations.

One limitation of this study was that data on cause of

death was missing for eight centenarians' offspring and

seven controls. These numbers are included in the total all-cause

mortality and, as such, do not change these findings.

The unknown causes of death could affect the results for

cancer-specific and coronary heart disease–specific causes

of death, but this would require six of the eight centenar-ians'

offspring with unknown cause of death and none of

the controls with unknown cause of death to have been

attributed to one category (i.e., coronary heart disease or

cancer) before statistical significance would have been lost.

Alternatively, if most of the controls with unknown cause of

death were attributed to coronary heart disease or cancer

and none of the centenarians' offspring were, then the

magnitude of the findings would be even stronger.

These results suggest that, to better understand familial

factors that confer an increased risk of achieving excep-tional

old age, it may be necessary to look beyond path-ogenic

mechanisms specific to cardiovascular disease and

include mechanisms common to cardiovascular disease and

cancer. Such mechanisms could include basic causes of ag-ing

and defenses against aging that would have a broad

influence upon susceptibility to age-related illnesses.8 For

example, genetic manipulation of insulin signaling and free-radical

production pathways have dramatic effects upon

lifespan in lower organisms.9–11 Genetic studies of cente-narians,

centenarians' offspring, and controls will perhaps

help to decipher whether such basic mechanisms are influ-ential

in achieving exceptional longevity in humans.

REFERENCES

1. Terry DF, Wilcox M, McCormick MAet al. Cardiovascular advantages

among

the offspring of centenarians. J Gerontol A Biol Sci Med Sci 2003;58A:

M425–M431.

2. Perls TT, Wilmoth J, Levenson R et al. Life-long sustained

mortality advantage

of siblings of centenarians. Proc Natl Acad Sci U S A 2002;99:8442–

8447.

3. Barzilai N, Atzmon G, Schechter C et al. Unique lipoprotein

phenotype and

genotype associated with exceptional longevity. JAMA 2003;290:2030–

2040.

4. Terry DF, Wilcox MA, McCormick MA et al. Cardiovascular disease

delay in

centenarian offspring. J Gerontol A Biol Sci Med Sci 2004;59A:M385–

M389.

5. DePinho RA. The age of cancer. Nature 2000;408:248–254.

6. Sinclair DA. Cell biology. An age of instability. Science

2003;301:1859–1860.

7. Wood RD, M, Sgouros J et al. Human DNA repair genes.

Science

2001;291:1284–1289.

8. Cutler RG. Evolution of human longevity and the genetic complexity

govern-ing

aging rate. Proc Natl Acad Sci U S A 1975;72:4664–4668.

9. Guarente L. Aging. What makes us tick? Science 1997;275:943–944.

10. Jazwinski SM. Longevity, genes, and aging. Science 1996;273:54–59.

11. Guarente L, Kenyon C. Genetic pathways that regulate ageing in

model

organisms. Nature 2000;408:255–262.

Table 1. Prevalence of Specific Causes of Mortality

in Centenarians' Offspring (n=295) Versus Controls (n=276)

_____________________________________________

Cause of Mortality Odds Ratio (95% CI)* P-value

______________________________________________

Total mortality 0.38 (0.24–0.58) <.001

Cancer 0.29 (0.13–0.66) .002

Cardiac 0.15 (0.04–0.51) <.001

Aneurysm 0.48 (0.44–0.52) .05

Childhood 1.74 (0.64–4.78) .28

Stroke 0.23 (0.03–2.08) .20

Neurological 1.88 (0.17–20.8) 1.00

Accident 0.18 (0.02–1.59) .11

Miscellaneous** 0.39 (0.10–1.54) .21

Unknown 1.07 (0.38–2.99) .90

__________________________________

* Statistics were calculated by comparing the number

who died from each cause with the total sample.

**Liver disease, primary amyloidosis, suicide,

pulmonary fibrosis, and surgical complications.

Cheers, Alan Pater

--- In , " Rodney " <perspect1111@y...>

wrote:

>

> Hi folks:

>

> http://www.foxnews.com/story/0,2933,140374,00.html

>

> Rodney.