The hippocampus shrinks in late adulthood, leading to impaired memory and increased risk for dementia. Hippocampal and medial temporal lobe volumes are larger in higher-fit adults, and physical activity training increases hippocampal perfusion, but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown. Here we show, in a randomized controlled trial with 120 older adults, that aerobic exercise training increases the size of the anterior hippocampus, leading to improvements in spatial memory. Exercise training increased hippocampal volume by 2%, effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF, a mediator of neurogenesis in the dentate gyrus. Hippocampal volume declined in the control group, but higher preintervention fitness partially attenuated the decline, suggesting that fitness protects against volume loss. Caudate nucleus and thalamus volumes were unaffected by the intervention. These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood, which is accompanied by improved memory function.eterioration of the hippocampus precedes and leads to memory impairment in late adulthood (1, 2). Strategies to fight hippocampal loss and protect against the development of memory impairment has become an important topic in recent years from both scientific and public health perspectives. Physical activity, such as aerobic exercise, has emerged as a promising lowcost treatment to improve neurocognitive function that is accessible to most adults and is not plagued by intolerable side effects often found with pharmaceutical treatments (3). Exercise enhances learning and improves retention, which is accompanied by increased cell proliferation and survival in the hippocampus of rodents (4-6); effects that are mediated, in part, by increased production and secretion of BDNF and its receptor tyrosine kinase trkB (7,8).Aerobic exercise training increases gray and white matter volume in the prefrontal cortex (9) of older adults and increases the functioning of key nodes in the executive control network (10, 11). Greater amounts of physical activity are associated with sparing of prefrontal and temporal brain regions over a 9-y period, which reduces the risk for cognitive impairment (12). Further, hippocampal and medial temporal lobe volumes are larger in higher-fit older adults (13,14), and larger hippocampal volumes mediate improvements in spatial memory (13). Exercise training increases cerebral blood volume (15) and perfusion of the hippocampus (16), but the extent to which exercise can modify the size of the hippocampus in late adulthood remains unknown.To evaluate whether exercise training increases the size of the hippocampus and improves spatial memory, we designed a singleblind, randomized controlled trial in which adults were randomly assigned to receive either moderate-...

Hippocampal volume shrinks in late adulthood, but the neuromolecular factors that trigger hippocampal decay in aging humans remains a matter of speculation. In rodents, brain-derived neurotrophic factor (BDNF) promotes the growth and proliferation of cells in the hippocampus and is important in long-term potentiation and memory formation. In humans, circulating levels of BDNF decline with advancing age, and a genetic polymorphism for BDNF has been related to gray matter volume loss in old age. In this study, we tested whether age-related reductions in serum levels of BDNF would be related to shrinkage of the hippocampus and memory deficits in older adults. Hippocampal volume was acquired by automated segmentation of magnetic resonance images in 142 older adults without dementia. The caudate nucleus was also segmented and examined in relation to levels of serum BDNF. Spatial memory was tested using a paradigm in which memory load was parametrically increased. We found that increasing age was associated with smaller hippocampal volumes, reduced levels of serum BDNF, and poorer memory performance. Lower levels of BDNF were associated with smaller hippocampi and poorer memory, even when controlling for the variation related to age. In an exploratory mediation analysis, hippocampal volume mediated the age-related decline in spatial memory and BDNF mediated the age-related decline in hippocampal volume. Caudate nucleus volume was unrelated to BDNF levels or spatial memory performance. Our results identify serum BDNF as a significant factor related to hippocampal shrinkage and memory decline in late adulthood.

Exercise training (EX) may decrease adipose tissue inflammation, thereby ameliorating such disturbances, even in the absence of fat loss. The purpose of this study was to 1) compare the effects of low-fat diet (LFD), EX, and their combination on inflammation, insulin resistance, and hepatic steatosis in high-fat diet-induced obese mice and 2) determine the effect of intervention duration (i.e., 6 vs. 12 wk). C57BL/6 mice (n ϭ 109) fed a 45% fat diet (HFD) for 6 wk were randomly assigned to an EX (treadmill: 5 days/wk, 6 or 12 wk, 40 min/day, 65-70% V O2max) or sedentary (SED) group. Mice remained on HFD or were placed on a 10% fat diet (LFD) for 6 or 12 wk. Following interventions, fat pads were weighed and expressed relative to body weight; hepatic steatosis was assessed by total liver triglyceride and insulin resistance by HOMA-IR and glucose AUC. RT-PCR was used to determine adipose gene expression of MCP-1, F4/80, TNF-␣, and leptin. By 12 wk, MCP-1, F4/80, and TNF-␣ mRNA were reduced by EX and LFD. Exercise (P ϭ 0.02), adiposity (P ϭ 0.03), and adipose F4/80 (P ϭ 0.02) predicted reductions in HOMA-IR (r 2 ϭ 0.75, P Ͻ 0.001); only adiposity (P ϭ 0.04) predicted improvements in hepatic steatosis (r 2 ϭ 0.51, P Ͻ 0.001). Compared with LFD, EX attenuated increases in adiposity, hepatic steatosis, and adipose MCP-1 expression from 6 to 12 wk. There are unique metabolic consequences of a sedentary lifestyle and HFD that are most evident long term, highlighting the importance of both EX and LFD in preventing obesity-related metabolic disturbances. obesity; insulin resistance; hepatic steatosis; macrophage OBESITY RESULTS FROM AN ENERGY IMBALANCE attributable to our current lifestyle, which includes little physical activity and excessive intake of foods high in saturated and trans fats and refined carbohydrates. Consumption of a high-fat Western diet (HFD) and physical inactivity are potential triggers of chronic diseases such as type 2 diabetes and cardiovascular disease. Insulin resistance (IR) and lipid accumulation in the liver are two common metabolic changes that increase the risk of such chronic diseases. It is now recognized that hepatic steatosis (the initial stage of nonalcoholic fatty liver disease) and insulin resistance should be targeted early to prevent complications associated with these conditions. Visceral white adipose tissue (WAT) is currently believed to be the key depot linked with obesity-related systemic metabolic disturbances (6). WAT becomes inflamed during adipose tissue hypertrophy due to an influx of macrophages (M⌽s) that secrete proinflammatory cytokines, including tumor necrosis factor (TNF)-␣. The cause of M⌽ influx into WAT is not completely understood, but an increase in the gene expression of monocyte chemoattractant protein-1 (MCP-1) in WAT has been shown to precede M⌽ entry, suggesting that this chemokine plays an important role in WAT M⌽ accumulation (15).Attenuating inflammation in WAT beneficially modifies (15) these metabolic disturbances and reduces disease risk, even in th...

. Exercise accelerates cutaneous wound healing and decreases wound inflammation in aged mice.

Participants randomized to cardiovascular exercise experienced improvements in influenza seroprotection throughout the entire influenza season, whereas those in the balance and flexibility intervention did not. Although there were no differences in reported respiratory tract infections, the exercise group exhibited reduced overall illness severity and sleep disturbance. These data support the hypothesis that regular endurance exercise improves influenza vaccine responses.