Aging Clinical and Experimental Research

Kirkwood, T.; Franceschi, C.

doi: 10.1007/BF03324119pmid: 8481421

Sohal, R.

doi: 10.1007/BF03324120pmid: 8386942

The objective of this review article is to assess the current status of the predictions of the free radical hypothesis of aging, highlighting some of the controversies surrounding the previous assumptions. Topics for discussion include: metabolic rate and aging, oxidative stress and molecular damage during aging, antioxidants and aging, antioxidant defenses and life spans of different species, and pro-oxidant generation and aging. On the basis of currently available evidence, it is concluded that the free radical hypothesis has neither been proven nor disproven. Some of the earlier assumptions such as that antioxidant intake increases life span, or antioxidant defenses decline with age, or antioxidant defenses are positively correlated with life spans of different species, or that longer life spans are associated with lower autoxidizability, are not clearly supportable. Similarly, the assumption that oxygen free radicals govern the rate of aging via the infliction of molecular damage lacks compelling support. Enough information to lift the free radical hypothesis above the level of speculation has not yet been amassed. Clearly, further studies, some of which specifically focus on disproving this hypothesis, are needed to confirm its veracity. (Aging Clin. Exp. Res. 5: 3–17, 1993)

doi: 10.1007/BF03324121pmid: N/A

Postiglione, Alfredo; Lassen, N.; Holman, B.

doi: 10.1007/BF03324122pmid: 8481422

In the normal brain as well as in Alzheimer’s disease (AD), regional cerebral blood flow (CBF) is coupled to metabolic demand and, therefore, changes in CBF reflect variations in neuronal metabolism. The use of radionuclide techniques, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT), provides an accurate assessment of regional functional activity, i.e., CBF and metabolism, and could be very helpful for the differential diagnosis of AD. This disease is characterized by a decrease in global CBF and metabolism. When found, a symmetric bi-parieto-temporal CBF reduction is highly diagnostic for AD, despite the fact that a similar CBF pattern could also be observed in other types of dementia. Many AD patients with parieto-temporal flow reduction also have a diffuse flow reduction in the frontal cortical areas, particularly in advanced stages of the disease. Lateral CBF asymmetry is also very frequent; speech disorders are highly characteristic of left-sided flow reduction, while visuospatial apraxia is dominating in the right-sided cases. In advanced and severe cases of AD, CBF and metabolism tend to be more uniformly reduced throughout the cortex, sparing only the primary visual and sensory-motor cortices. PET and SPECT measurement of brain perfusion and metabolism has added a new dimension to the knowledge of dementia disorders, with a better differential diagnosis between AD and other forms of dementia. The correlation with neuropsychological data has also given new insight into the disease. (Aging Clin. Exp. Res. 5: 19–26, 1993)

Huntley, Joan; Ostfeld, A.; Taylor, J.; Wallace, R.; Blazer, D.; Berkman, L.; Evans, D.; Kohout, J.; Lemke, J.; Scherr, P.; Korper, S.

doi: 10.1007/BF03324123pmid: 8481423

doi: 10.1007/BF03324124pmid: N/A

Murialdo, Giovanni; Costelli, P.; Fonzi, S.; Parodi, C.; Torre, F.; Cenacchi, T.; Pollen, A.

doi: 10.1007/BF03324125pmid: 8481424

Alterations in periodical functions are known to occur in aging and may be regarded as markers of the aging process itself. Melatonin and Thyroid Stimulating Hormone (TSH) circadian periodicities were studied in 22 aged subjects and in 13 adult controls. The study of rhythmicity was performed by the Cosinor analysis. Elderly subjects were hospitalized because of various concomitant diseases. Circadian periodicity of both hormones was disrupted in the aged group, and the deterioration of melatonin periodicity was significantly correlated with the decay in cognitive functions, quantified by the Mini Mental State evaluation. Diabetes was also found to affect, though not significantly, melatonin, but not TSH, periodicity. Melatonin and TSH nocturnal peaks were decreased in aged people. TSH oscillation amplitudes were inversely correlated with age. No correlation was found between melatonin and TSH secretory features both in adult and in aged subjects. (Aging Clin. Exp. Res. 5: 39–46, 1993)

Elmståhl, Sölve; Gärdsell, P.; Ringsberg, K.; Sernbo, I.

doi: 10.1007/BF03324126pmid: 8481425

A higher incidence of fragility fractures in urban than in rural populations has been described. The present study included 954 randomly selected men and women between the ages of 40 to 80 years living in the cities of Malmö, an urban population, and Sjöbo, a typical agricultural community. Lean body mass (LBM) was estimated with a bioelectrical impedance method; bone mineral content (BMC) of the forearm was evaluated by single photon absorptiometry, and strength of the quadriceps, and hamstring muscles of the right knee, and hand grip were measured. The age-related difference in LBM between the ages of 50 to 80 were 7.8 kg in men and 2.9 kg in women. Urban men aged 60 and 70, and women aged 50 and 70 had a 1.8 to 3.7 kg lower LBM than rural subjects. One hundred women(17%) and 28 men (11%) had experienced fragility fractures. Women aged 70 with fragility fractures had 3.1 kg lower LBM than women without fractures, and the age-dependent difference in LBM was greater in the urban and rural women with fracture, than in women without fracture. LBM showed a higher correlation to BMC, in the range of 0.20–0.28, than the correlation between body weight and BMC. Quadriceps muscle strength was lower in the elderly age groups in both sexes, and a 40% decline was seen both in those from the highest and lowest quartiles of LBM. Use of LBM instead of body weight showed higher correlations to flexion strength of the knee and hand grip. The differences in body composition between an urban and a rural population could probably be attributed to differences in life-style factors, such as physical activity. Overall results show the importance of a maintained lean body mass. (Aging Clin. Exp. Res. 5: 47–54, 1993)

Cheng, Sulin; Suominen, H.; Heikkinen, E.

doi: 10.1007/BF03324127pmid: 8481426

Bone mineral content (BMC, gem−2) and density (BMD, gem−3) were studied in 75-year-old men and women in relation to anthropometric and certain life-style factors. This study covered all the men and women born in 1914 who were residents in the city of Jyväskylä in 1989 (N=388). A hundred and three men and 188 women participated in bone measurements performed at the calcaneus using a 125I-photon absorption method. BMC was on average 36% and BMD 17% higher in the men than in the women. BMC and BMD associated with body mass in both sexes, and with body fat and use of estrogen in the women. There was a negative correlation between the BMD values and the number of cigarettes smoked over the entire life course in both sexes. Moderate physical activity was related to higher BMC in the men. Men and women who had been physically active earlier in their life tended to show higher BMD values than those who had been more sedentary. (Aging Clin. Exp. Res. 5: 55–62, 1993)

Passen, M.; Cucinotta, D.; Abate, G.; Senin, U.; Ventura, A.; Stramba Badiale, M.; Diana, R.; La Greca, P.; Grazie, Cristina

doi: 10.1007/BF03324128pmid: 8257478

5′-Methyltetrahydrofolic acid (5′- MTHF) in addition to standard psychotropic medication significantly improved clinical recovery in depressed patients with borderline or definite folate deficiency, and significantly reduced depressive symptoms in elderly normofolatemic patients after 3 weeks of treatment. In this equivalence study the effect of 5′- MTHF on depressive symptoms and cognitive status was compared to Trazodone (TRZ) in normofolatemic elderly patients with mild to moderate dementia and depression. Ninety-six patients with dementia, scoring 12–23 at the Mini Mental State Examination (MMSE) and ≥18 at the Hamilton Depression Rating Scale (HDRS) after a 2-week placebo run-in, were randomized to receive either 5′-MTHF (50 mg/day p.o.) (47 patients) or TRZ (100 mg/day p.o.) (49 patients) in a double-blind design for 8 weeks. HDRS was assessed before, after 4 weeks and at the end of treatment; Rey’s Verbal Memory (RVM) test for immediate and delayed recall was evaluated before and after treatment. After 4 weeks of treatment HDRS score was reduced from 23±5 to 20±6 in the 5′-MTHF (p<0.05 vs baseline), and from 23±3 to 21±4 in the TRZ group (p<0.05 vs baseline). p]A further significant decrease to 18±6 and 19±5 respectively was obtained at the end of the treatment period (p<0.05 vs week 4) with 5′-MTHF and TRZ. HDRS was administered again after a 4-week, drug-free, follow-up period: no change vs the post treatment scores was observed either in the 5′-MTHF or in the TRZ group (18±7 and 19±5 respectively). RVM test for immediate recall was significantly improved (p<0.05) at week 8 vs baseline in the 5′-MTHF group whereas no significant change occurred in the TRZ group. No change in delayed recall was observed after treatment in either group. Tolerability was good for both treatments. This study shows that 5′-MTHF and TRZ are equally effective in improving depressive symptoms in patients with mild to moderate dementia and suggests that pharmacological doses of 5′-MTHF may exert psychotropic effects irrespective of folate status. (Aging Clin. Exp. Res. 1: 63–71, 1993)