| Accumulated wear and tear |
| Free-radical damage and
oxidative stress |
Endogenous or exogenous
free radicals
[11,
12].
|
Damage to proteins
(glycation), lipids and DNA [36,43,
44,45,48].
|
Cancer, cataracts, atherosclerosis and Alzheimer's plaques.
|
Yes: Can cause DNA DSBs, apoptosis and inflammation [16,
53,81].
|
| Mito-chondrial damage |
Endogenous
electron leakage
[12].
|
Increased 8-oxo-dG lesions in mitochondrial DNA and decreased
repair [83].
|
Cancer and neurodegeneration
[37].
|
Yes: 8X more γ-ray oxidative damage to mitochondrial
than nuclear DNA [39].
|
| Rate of living |
The higher the metabolic
rate, the shorter the life span [160].
|
Oxidative damage increases
with metabolic rate [161].
|
Calorie restriction lowers
body temperature, increases life span [154].
|
No: Ability to change metabolic rate not found in
literature.
|
| Telomere shortening |
Oxidative stress [93].
|
Shorter telomeres lead to
replicative senescence [91,95].
|
Cardiovascular disease [98, 97]. Segmental
aging in some progerias [138].
|
Ambiguous: No change in telomere length [102]. Short
telomeres increase sensitivity to radiation [103,105].
|
| Programmed senescence and
other processes |
| Telomere shortening |
"Mitotic clock" [90]
|
As above.
|
As above.
|
As above.
|
|
Senile endocrineand auto-immune response
|
Hypothalamus receptor
insensitivity and increased autoimmunity [162].
|
Hyperinsulinemia, reduced innate
and adaptive immune response (immunosenescence) and increased autoimmune
antibodies [163].
|
Diabetes, autoimmune hypothyroidism, rheumatoid arthritis.
|
No: No dose response for autoimmune hypothyroidism and rheumatoid arthritis in A-bomb survivors
[15,26].
Excess type 2 diabetes only at high doses [142].
|
| Immunological decline |
Hormone levels.
|
Decreased naïve T-cells and
lymphocytes [23].
|
Viral and bacterial
infections, i.e., pneumonia.
|
Ambiguous: Evidence of immunological decline in A-bomb survivors [23, 53, 54], but
infectious disease is not in excess [30].
|
| ‘Metabolic' aging |
Metabolic syndrome and
activation of the TOR pathway [152].
|
Increased insulin
resistance, blood glucose and leptin.
|
Diabetes, cardiovascular
disease, stroke, hypertension and dementia
|
Ambiguous: A-bomb survivors show high blood pressure and cholesterol,
excess atherosclerosis, but no excess diabetes and dementia [15,19,20].
|
