MUFAs And Longevity

Here is a paper from several years ago showing a link between mono-unsaturated fatty acids (MUFAs) and longevity in the worm Caenorhabditis elegans.  A molecular mechanism is given - worms deficient in a particular enzyme that modifies DNA and hence affects gene expression exhibit accumulation of MUFas and a longer lifespan. Dietary MUFAs were shown be able to enhance lifespan.  Perhaps this applies to mammals, including humans? Abstract:

Chromatin and metabolic states both influence lifespan, but how they interact in lifespan regulation is largely unknown. The COMPASS chromatin complex, which trimethylates lysine 4 on histone H3 (H3K4me3), regulates lifespan in Caenorhabditis elegans. However, the mechanism by which H3K4me3 modifiers affect longevity, and whether this mechanism involves metabolic changes, remain unclear. Here we show that a deficiency in H3K4me3 methyltransferase, which extends lifespan, promotes fat accumulation in worms with a specific enrichment of mono-unsaturated fatty acids (MUFAs). This fat metabolism switch in H3K4me3 methyltransferase-deficient worms is mediated at least in part by the downregulation of germline targets, including S6 kinase, and by the activation of an intestinal transcriptional network that upregulates delta-9 fatty acid desaturases. Notably, the accumulation of MUFAs is necessary for the lifespan extension of H3K4me3 methyltransferase-deficient worms, and dietary MUFAs are sufficient to extend lifespan. Given the conservation of lipid metabolism, dietary or endogenous MUFAs could extend lifespan and healthspan in other species, including mammals.

Targeting Senescent Cells

Here is a paper from several years ago suggesting that targeting senescent cells with programmed cell death can reverse aspects of aging in mice.  Older studies suggested rapamycin or carnosine as anti-aging interventions. We will be keeping track of further developments in this field.

Age And Triathlon Performance

How does Ironman triathlon performance change with age?  Abstract:

In Ironman triathlon, the number of overall male and female finishers increased in the last 30 years, while an improvement in performance has been reported. Studies concluding these numbers only analysed the top ten athletes per age group instead of all finishers, therefore a selection bias might have occurred. The aim of the present study was to investigate participation, performance and the age-related performance decline of all pro and age group triathletes ranked in all Ironman triathlons held worldwide between 2002 and 2015. Split and overall race times of 329,066 (80%) male and 81,815 (20%) female athletes competing in 253 different Ironman triathlon races were analysed. The number of finishers increased in all age groups with exception of women in age group 75-79 years. In pro athletes, performance improved in all disciplines. In age group athletes, performance improved in younger age groups for running (18-24 to 40-44 years) and older age groups for swimming (50-54 to 65-69 years) and cycling (35-39 to 55-59 years), while it impaired in younger age groups for swimming (18-24 to 45-49 years) and cycling (18-24 to 30-34), and older age groups in running (45-49 to 70-74 years). The age-related performance decline started in women in age group 25-29 years in swimming and in age group 30-34 years in cycling, running and overall race time, whereas it started in men in age group 25-29 years in swimming and in age group 35-39 years in cycling, running and overall race time. For athletes and coaches, performance improved in younger age groups for running and older age groups for swimming and cycling and the age-related decline in performance started earlier in swimming than in cycling and running. In summary, women should start competing in Ironman triathlon before the age of 30 years and men before the age of 35 years to achieve their personal best Ironman race time.

It is interesting that performance in swimming declined earlier with age than in cycling and running, suggesting that swimming is the most intense exercise of the three.  The last sentence suggests that Ironman  is best for the young.

Meal Delivery And Elder Feeding

Home-delivered meal programs help elder diets, abstract:

BACKGROUND:

Poor diet quality and insufficient nutrient intake is of particular concern among older adults. The Older Americans Act of 1965 authorizes home-delivered meal services to homebound individuals aged 60 years and older.

OBJECTIVE:

The purpose of this study was to review scientific evidence on the impact of home-delivered meal services on diet and nutrition among recipients.

METHODS:

Keyword and reference searches were conducted in Cochrane Library, Google Scholar, PubMed and Web of Science. Inclusion criteria included: study design (randomized controlled trials, cohort studies, pre-post studies, or cross-sectional studies); main outcome (food and nutrient intakes); population (home-delivered meal program participants); country (US); language (articles written in English); and article type (peer-reviewed publications or theses).

RESULTS:

Eight studies met the inclusion criteria, including two randomized controlled trial studies (from the same intervention), one cohort study, two pre-post studies, and three cross-sectional studies. All but two studies found home-delivered meal programs to significantly improve diet quality, increase nutrient intakes, and reduce food insecurity and nutritional risk among participants. Other beneficial outcomes include increased socialization opportunities, improvement in dietary adherence, and higher quality of life.

CONCLUSIONS:

Home-delivered meal programs improve diet quality and increase nutrient intakes among participants. These programs are also aligned with the federal cost-containment policy to rebalance long-term care away from nursing homes to home- and community-based services by helping older adults maintain independence and remain in their homes and communities as their health and functioning decline.

As families are scattered about, particularly in the USA, it is important that some infrastructure exists to ensure older people have adequate dietary intake.

High Intensity Exercise And Age

There is the popular misconception that high intensity exercise is for the young, and the aging should just shuffle around a little bit and call it a day.

This paper from several years ago says otherwise.  This doesn't mean an elderly person needs to be doing a "Heavy Duty Mike Mentzer" bodybuilding workout, but there needs to be sufficient stimulus for the exercise to be effective.  Thus, the authors talk about the benefits of "low volume, high-intensity aerobic and/or resistance training" to achieve a variety of health benefits.

Of course, at any age, consult your physician before starting any exercise program, but we see a clear indication that high volume, low intensity does not need to be the way to go for the aging.  High intensity can do a better job.

Overuse Injuries In Endurance Athletes

Of interest is this paper on overuse injuries in endurance athletes, abstract:

AIM:

The purpose of this study was to clarify training-related risk factors for overuse injuries.

METHODS:

This was twelve-month retrospective study which was done by self-reported postal questionnaire. The study group consisted of 446 men and women top-level Finnish athletes representing three different endurance sports (cross-country skiing, swimming, long-distance running) between the ages of 15-35. Self-reported anthropometric and training-related variables (such as starting age of training, years of active training, hours trained yearly, competition hours and weekly resting days) and occurrence of overuse injuries.

RESULTS:

Athletes with less than 2 rest days per week during the training season had 5.2-fold risk (95% confidence intervals [CI] 1.89-14.06, P=0.001) for an overuse injury, and athletes who trained more than 700 hours during a year had 2.1-fold risk (95% CI 1.21-3.61, P=0.008) for an overuse injury compared to the others. Athletes who reported a tendon injury were on average two years older than athletes without such an injury (P<0.001).

CONCLUSION:

We found that low number of recovery days and a high amount of training are training-related risk factors for overuse injuries in top-level endurance athletes. The higher number of tendon overuse injuries in older than younger athletes may indicate that age-related degeneration plays an important role in the etiology of tendon injuries. These findings should be taken into account when planning exercise programs for endurance athletes.

The conclusions seem to be relevant for the more casual athlete and average person exercising as well, when one considers that insufficient recovery and excessive training are risk factors for overuse injuries in elite athletes.  The age factor is also very likely relevant as well. If we assume relevance for athletes at all levels of ability and experience, one should plan their exercise programs to incorporate sufficient recovery time, avoid excess training - and these recommendations would be especially important for the older athlete.

Prevent Aging With Stem Cell Rejuvenation?

Discussion of a possible anti-aging approach, abstract:

Characterized by dysfunction of tissues, organs, organ systems and the whole organism, aging results from the reduced function of effective stem cell populations. Recent advances in aging research have demonstrated that old tissue stem cells can be rejuvenated for the purpose of maintaining the old-organ function by youthful re-calibration of the environment where stem cells reside. Biochemical cues regulating tissue stem cell function include molecular signaling pathways that interact between stem cells themselves and their niches. Historically, plasma fractions have been shown to contain factors capable of controlling age phenotypes; subsequently, signaling pathways involved in the aging process have been identified. Consequently, modulation of signaling pathways such as Notch/Delta, Wnt, transforming growth factor-β, JAK/STAT, mammalian target of rapamycin and p38 mitogen-activated protein kinase has demonstrated potential to rejuvenate stem cell function leading to organismic rejuvenation. Several synthetic agents and natural sources, such as phytochemicals and flavonoids, have been proposed to rejuvenate old stem cells by targeting these pathways. However, several concerns still remain to achieve effective organismic rejuvenation in clinical settings, such as possible carcinogenic actions; thus, further research is still required.

Note the point at the end about "possible carcinogenic actions."  Paradox: while the risk of most cancers increases with age, aging itself can be viewed as an anti-cancer mechanism, diminishing cell reproduction and stem cell activity (and elimination of stem cells) to prevent such cells with mutations from multiplying into tumors.  Thus, anti-aging approaches need to be cognizant of the cancer problem and find solutions to this possible problem.

Dietary Interventions For Sarcopenia

Sarcopenia is the loss of muscle with normal aging.  What dietary interventions can help improve muscle mass in these patients?  Abstract:

BACKGROUND: Inadequate nutritional intake and altered response of aging muscles to anabolic stimuli from nutrients contribute to the development of sarcopenia. Nutritional interventions show inconsistent results in sarcopenic older adults, which might be influenced by their basal nutritional status.

OBJECTIVE: To test if baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations and dietary protein intake influenced changes in muscle mass and function in older adults who received nutritional intervention.

METHODS AND DESIGN: Post-hoc analysis was performed in the PROVIDE study that was a randomized controlled, double blind trial among 380 sarcopenic older adults. This study showed that those who received a vitamin D and leucine-enriched whey protein medical nutrition drink for 13 weeks gained more appendicular muscle mass (aMM), and improved lower-extremity function as assessed by the chair stand test compared with controls. To define low and high groups, a baseline serum concentration of 50 nmol/L 25(OH)D and baseline dietary protein intake of 1.0 g/kg/d were used as cut offs.

RESULTS: At baseline, participants with lower 25(OH)D concentrations showed lower muscle mass, strength and function compared with participants with a high 25(OH)D, while the group with lower protein intake (g/kg/day) had more muscle mass at baseline compared with the participants with higher protein intake. Participants with higher baseline 25(OH)D concentrations and dietary protein intake had, independent of other determinants, greater gain in appendicular muscle mass, skeletal muscle index (aMM/h2), and relative appendicular muscle mass (aMM/body weight × 100%) in response to the nutritional intervention. There was no effect modification of baseline 25(OH)D status or protein intake on change in chair-stand test.

CONCLUSIONS: Sufficient baseline levels of 25(OH)D and protein intake may be required to increase muscle mass as a result of intervention with a vitamin D and protein supplement in sarcopenic older adults. This suggests that current cut-offs in the recommendations for vitamin D and protein intake could be considered the "minimum" for adults with sarcopenia to respond adequately to nutrition strategies aimed at attenuating muscle loss.

It may not be surprising that patients with higher baseline vitamin D and protein intake showed greater muscle gains when given the enriched drink intervention.  It is curious that at baseline, while the higher vitamin D intake group had greater muscle mass, it was the lower protein intake group that had greater muscle mass.  The higher protein intake group had more women that the lower group, less weight and less fat, so there are a number of factors to consider.  The bottom line though is that gain of muscle above baseline required sufficient vitamin D and protein.

Nervous System Immune Cells

There are distinct populations of central nervous system immune cells comparing states of health, aging, and disease Alzheimer's disease and multiple sclerosis). This may assist in devising new therapeutic strategies against those diseases as well as giving insights into the human aging process. Abstract:

Individual reports suggest that the central nervous system (CNS) contains multiple immune cell types with diverse roles in tissue homeostasis, immune defense, and neurological diseases. It has been challenging to map leukocytes across the entire brain, and in particular in pathology, where phenotypic changes and influx of blood-derived cells prevent a clear distinction between reactive leukocyte populations. Here, we applied high-dimensional single-cell mass and fluorescence cytometry, in parallel with genetic fate mapping systems, to identify, locate, and characterize multiple distinct immune populations within the mammalian CNS. Using this approach, we revealed that microglia, several subsets of border-associated macrophages and dendritic cells coexist in the CNS at steady state and exhibit disease-specific transformations in the immune microenvironment during aging and in models of Alzheimer's disease and multiple sclerosis. Together, these data and the described framework provide a resource for the study of disease mechanisms, potential biomarkers, and therapeutic targets in CNS disease. 

Aging And Heart Failure Links

The obvious aging-heart failure link has links to cell signaling; understanding these links can lead to novel therapies.  Abstract:

The molecular pathophysiology of heart failure, which is one of the leading causes of mortality, is not yet fully understood. Heart failure can be regarded as a systemic syndrome of aging-related phenotypes. Wnt/β-catenin signaling and the p53 pathway, both of which are key regulators of aging, have been demonstrated to play a critical role in the pathogenesis of heart failure. Circulating C1q was identified as a novel activator of Wnt/β-catenin signaling, promoting systemic aging-related phenotypes including sarcopenia and heart failure. On the other hand, p53 induces the apoptosis of cardiomyocytes in the failing heart. In these molecular mechanisms, the cross-talk between cardiomyocytes and non-cardiomyocytes (e,g,. endothelial cells, fibroblasts, smooth muscle cells, macrophages) deserves mentioning. In this review, we summarize recent advances in the understanding of the molecular pathophysiology underlying heart failure, focusing on Wnt/β-catenin signaling and the p53 pathway.

Economic Costs Of An Inactive Aging Population

Aging, inactive populations result in costs, including economic costs, on nation and society.  This applies to Germany and most other developed nations) and approaches to stimulate physical activity and promote good health among the aging population.  Abstract:

BACKGROUND:

Aging societies represent a major challenge for health care systems all over the world. As older people tend to be more physically inactive, economic costs of inactivity are likely to increase notably. The present study aims to investigate this relationship between an aging society and economic costs of inactivity using the example of Germany.

METHODS:

Using data from the German Socio-Economic Panel, this study applied the comparative risk assessment method developed by the WHO to estimate the direct costs of inactivity for the period 2001-2013 differentiated by gender-specific age-groups (15-29; 30-44; 45-64; 65+). Based on population statistics predicting the aging of the German population for the years 2014-2060, this research projects the development of future costs of inactivity and potential effects of interventions promoting physical activity among the German population.

RESULTS:

The results reveal an increase in the level of physical activity during the observed period (2001-2013) which compensated the negative effect of aging and resulted in a decline of inactivity costs. The projections for the years 2014-2060 indicate a constant increase in direct per capita costs until 2060 because of an aging society. Scenarios indicating how a short-term reduction of physical inactivity impacts costs of inactivity reveal the crucial role of the oldest age-group in this context.

CONCLUSION:

The findings indicate that the aging of the German population demands further actions and initiatives to promote physical activity, especially for the oldest age-group.

Fasting And Stem Cell Function

In mice, a 24 hour fast improves the function of intestinal stem cells through effects on fatty acid oxidation (FAO).  Genetic knockout experiments emphasize the importance of FAO in the fasting effects and suggest possibilities for boosting intestinal stem cell regeneration.  Abstract:

Diet has a profound effect on tissue regeneration in diverse organisms, and low caloric states such as intermittent fasting have beneficial effects on organismal health and age-associated loss of tissue function. The role of adult stem and progenitor cells in responding to short-term fasting and whether such responses improve regeneration are not well studied. Here we show that a 24 hr fast augments intestinal stem cell (ISC) function in young and aged mice by inducing a fatty acid oxidation (FAO) program and that pharmacological activation of this program mimics many effects of fasting. Acute genetic disruption of Cpt1a, the rate-limiting enzyme in FAO, abrogates ISC-enhancing effects of fasting, but long-term Cpt1a deletion decreases ISC numbers and function, implicating a role for FAO in ISC maintenance. These findings highlight a role for FAO in mediating pro-regenerative effects of fasting in intestinal biology, and they may represent a viable strategy for enhancing intestinal regeneration.

Dietary Polyphenols And Preventing Cognitive Decline With Aging

Dietary polyphenols, by affecting cell signaling, can prevent declining nerve growth in adults and counteract cognitive decline due to age.  Such dietary components are found at high levels in fruit, but not in doughnuts, by the way, not that I want to “fat shame” anyone.  Abstract:

The increased number of elderly people worldwide poses a major medical and socio-economic challenge: the search of strategies to combat the consequences of the aging process. Oxidative stress and inflammation have been pointed out as the leading causes of brain aging, which in turn alters the functionality of brain. In this context, decline in adult neurogenesis (AN), due to modifications in the neural progenitor stem cells (NSCs) and their microenvironment, is among the aging alterations contributing to cognitive decline. Therefore, the consumption or administration of antioxidant and anti-inflammatory molecules, such as dietary polyphenols, is under study as a potential beneficial strategy for preventing brain aging alterations including AN decline. Polyphenols, through their antioxidant and anti-inflammatory properties, modulate several cascades and effectors involved in the regulation of AN (e.g., SIRT1, Wnt, NF-κB and Nrf2, among others). This work summarizes the latest discoveries regarding the mechanisms whereby polyphenols preserve AN and counteract the cognitive decline present in aging.

Aging, Androgens, Wnt, And Muscle

Fewer androgen receptors in muscle with age leads to less Wnt5a expression and that leads to less muscle - one explanation for muscle loss with age?  This study was in rats. Abstract:

We sought to determine whether age-related gastrocnemius muscle mass loss was associated with parallel decrements in androgen receptor (AR) or select Wnt signaling markers. To test this hypothesis, serum free and total testosterone (TEST) as well as gastrocnemius AR and Wnt signaling markers were analyzed in male Fischer 344 rats that were 3/6/12/18 and 24 months (mo) old (n=9 per group). Free and total TEST were greatest in 6 mo rats, and AR protein and Wnt5 protein levels linearly declined with aging. There were associations between Wnt5 protein levels and relative gastrocnemius mass (r=0.395, p=0.007) as well as AR and Wnt5 protein levels (r=0.670, p<0.001). We next tested the hypothesis that Wnt5 affects muscle fiber size by treating C2C12-derived myotubes lower (75 ng/mL) and higher (150 ng/mL) concentrations of recombinant Wnt5a protein. Both treatments increased myotube size (p<0.05) suggesting this ligand may affect muscle fiber size in vivo. We next tested if Wnt5a protein levels were androgen-modulated by examining 10 mo old male Fischer 344 rats (n=10-11 per group) that were orchiectomized and treated with testosterone-enanthate (TEST-E), trenbolone enanthate (TREN), a non-aromatizable synthetic testosterone analogue, or a vehicle (ORX only) for 4 weeks. Interestingly, TEST-E and TREN treatments increased Wnt5a protein in the androgen-sensitive levator ani/bulbocavernosus (LABC) muscle compared ORX only (p<0.05). To summarize, aromatizable and non-aromatizable androgens increase Wnt5a protein expression in skeletal muscle, age-related decrements in muscle AR may contribute Wnt5a protein decrements, and our in vitro data imply this mechanism may contribute to age-related muscle loss.

Cognitive Decline With Aging

Experiments with mice suggest that the aging brain accumulates astrocyte cells with an inflammatory phenotype that lose their normal function and release factors toxic to neurons.  This may also contribute to mental decline in aging humans.  These findings can eventually lead to approaches to reverse these processes.  Abstract:

The decline of cognitive function occurs with aging, but the mechanisms responsible are unknown. Astrocytes instruct the formation, maturation, and elimination of synapses, and impairment of these functions has been implicated in many diseases. These findings raise the question of whether astrocyte dysfunction could contribute to cognitive decline in aging. We used the Bac-Trap method to perform RNA sequencing of astrocytes from different brain regions across the lifespan of the mouse. We found that astrocytes have region-specific transcriptional identities that change with age in a region-dependent manner. We validated our findings using fluorescence in situ hybridization and quantitative PCR. Detailed analysis of the differentially expressed genes in aging revealed that aged astrocytes take on a reactive phenotype of neuroinflammatory A1-like reactive astrocytes. Hippocampal and striatal astrocytes up-regulated a greater number of reactive astrocyte genes compared with cortical astrocytes. Moreover, aged brains formed many more A1 reactive astrocytes in response to the neuroinflammation inducer lipopolysaccharide. We found that the aging-induced up-regulation of reactive astrocyte genes was significantly reduced in mice lacking the microglial-secreted cytokines (IL-1α, TNF, and C1q) known to induce A1 reactive astrocyte formation, indicating that microglia promote astrocyte activation in aging. Since A1 reactive astrocytes lose the ability to carry out their normal functions, produce complement components, and release a toxic factor which kills neurons and oligodendrocytes, the aging-induced up-regulation of reactive genes by astrocytes could contribute to the cognitive decline in vulnerable brain regions in normal aging and contribute to the greater vulnerability of the aged brain to injury.

Gut Micriobiota And Therapy For Aging-Related Diseases

Here’s an interesting paper linking the gut microbiota with therapies for aging-related diseases. Abstract:

Aging-associated alterations in composition, diversity and functional features of intestinal microbiota are well-described in the modern literature. They are suggested to be caused by an age-related decline in immune system functioning (immunosenescence) and a low-grade chronic inflammation (inflammaging), which accompany many aging-associated pathologies. The microbiota-targeted dietary and probiotic interventions have been shown to favorably affect the host health and aging by an enhancement of antioxidant activity, improving immune homeostasis, suppression of chronic inflammation, regulation of fat deposition and metabolism and prevention of insulin resistance. Recently, a high effectiveness and safety of novel therapeutic application such as fecal microbiota transplantation in the prevention and treatment of age-related pathological conditions including atherosclerosis, type 2 diabetes and Parkinson's disease has been demonstrated. In this review, recent research findings are summarized on the role of gut microbiota in aging processes with emphasis on therapeutic potential of microbiome-targeted interventions in anti-aging medicine.

The importance of the gut microbiota for overall good health and healthy aging cannot be overestimated. Interactions between the microbiota, the immune system, and prevalent diseases and disorders are an important emerging field in biomedicine and one which we will be watching closely.

High Fat Diet And the Aging Mouse Brain

A high fat diet seems not to be very good for aging of the mouse brain.  Fasting and a low fat diet seemingly have different effects.  Abstract:

Fasting may be exploited as a possible strategy for prevention and treatment of several diseases such as diabetes, obesity, and aging. On the other hand, high-fat diet (HFD) represents a risk factor for several diseases and increased mortality. The aim of the present study was to evaluate the impact of fasting on mouse brain aging transcriptome and how HFD regulates such pathways. We used the NCBI Gene Expression Omnibus (GEO) database, in order to identify suitable microarray datasets comparing mouse brain transcriptome under fasting or HFD vs aged mouse brain transcriptome. Three microarray datasets were selected for this study, GSE24504, GSE6285, and GSE8150, and the principal molecular mechanisms involved in this process were evaluated. This analysis showed that, regardless of fasting duration, mouse brain significantly expressed 21 and 30 upregulated and downregulated genes, respectively. The involved biological processes were related to cell cycle arrest, cell death inhibition, and regulation of cellular metabolism. Comparing mouse brain transcriptome under fasting and aged conditions, we found out that the number of genes in common increased with the duration of fasting (222 genes), peaking at 72 h. In addition, mouse brain transcriptome under HFD resembles for the 30% the one of the aged mice. Furthermore, several molecular processes were found to be shared between HFD and aging. In conclusion, we suggest that fasting and HFD play an opposite role in brain transcriptome of aged mice. Therefore, an intermittent diet could represent a possible clinical strategy to counteract aging, loss of memory, and neuroinflammation. Furthermore, low-fat diet leads to the inactivation of brain degenerative processes triggered by aging.

One can speculate about the human situation.

Aging And Dementia Links

Aging and dementia has common links, including the mitochondrial α-F1 -ATP synthase (ATP5A), which can be a target for the Alzheimer's disease drug candidate J147.  The mTOR signaling pathway is involved with this; abstract:

Aging is a major driving force underlying dementia, such as that caused by Alzheimer's disease (AD). While the idea of targeting aging as a therapeutic strategy is not new, it remains unclear how closely aging and age-associated diseases are coupled at the molecular level. Here, we discover a novel molecular link between aging and dementia through the identification of the molecular target for the AD drug candidate J147. J147 was developed using a series of phenotypic screening assays mimicking disease toxicities associated with the aging brain. We have previously demonstrated the therapeutic efficacy of J147 in several mouse models of AD. Here, we identify the mitochondrial α-F1 -ATP synthase (ATP5A) as a target for J147. By targeting ATP synthase, J147 causes an increase in intracellular calcium leading to sustained calcium/calmodulin-dependent protein kinase kinase β (CAMKK2)-dependent activation of the AMPK/mTOR pathway, a canonical longevity mechanism. Accordingly, modulation of mitochondrial processes by J147 prevents age-associated drift of the hippocampal transcriptome and plasma metabolome in mice and extends lifespan in drosophila. Our results link aging and age-associated dementia through ATP synthase, a molecular drug target that can potentially be exploited for the suppression of both. These findings demonstrate that novel screens for new AD drug candidates identify compounds that act on established aging pathways, suggesting an unexpectedly close molecular relationship between the two.

Overestimating Chronic Kidney Disease Frequency?

The frequency of chronic kidney disease may be overestimated due to not taking into account the normal decline in kidney function with age.  You’d think doctors, particularly nephrologists, would all know to make the necessary adjustments or normality for older patients, but apparently not. Abstract:

The process of glomerular filtration of plasma fluid has been known for over 160 years and the measurement of the rate of its formation (glomerular filtration rate, GFR) has been possible for over 80 years. Studies conducted in the 1930's to the 1950's clearly established that GFR declines, perhaps inexorably, with normal ageing, usually beginning after 30-40 years of age. The rate of decline may accelerate after age 50-60 years. This decline appears to be a part of the normal physiologic process of cellular and organ senescence and is associated with structural changes in the kidneys. In the last decade a new paradigm has been introduced in which the true or measured GFR is estimated (eGFR) by formulas based on serum creatinine levels and in which these estimates are applied to the diagnoses of chronic kidney disease (CKD) in the general population. These criteria for diagnosis of CKD include an absolute threshold for eGFR, unadjusted for the effects of age on the normal values for eGFR. A consequence of these criteria has been to overstate the frequency of CKD in the general population and to generate many "false positive" diagnoses of CKD. This paper discusses the known effects of ageing on GFR and the consequences of using a classification system for defining CKD that does not take into account the normal decline of GFR with ageing.

Aging And Body Repair

Aging is associated with a decline in the ability of the body to repair itself, including tissue and (at least partial) body part regeneration, with mechanisms that may include: “aging, increased Wnt signaling, NF-κB and tumor suppressor activity, and loss of positional information hampers regeneration.” This will enable, as the authors also state “safely activate endogenous regeneration in the elderly, and to generate a regeneration-permissive environment for cell therapies.”  Abstract:

Aging is associated with a significant decline of tissue repair and regeneration, ultimately resulting in tissue dysfunction, multimorbidity, and death. Salamanders possess remarkable regenerative abilities and have been studied with the prospect of inducing regeneration in humans and counteracting regenerative decline with aging. However, epimorphic regeneration, the full replacement of amputated structures, also occurs in mammals. One of the best studied models is digit tip regeneration, which is described for mice, and occurs in humans in a comparable manner. To accomplish regeneration, the amputated digit tip has to undergo three interdependent, overlapping steps: (i) wound healing without formation of a scar; (ii) formation of a blastema, a highly proliferative cell mass; and (iii) spatiotemporally regulated differentiation to generate a pattern similar to the original structure. Aging likely interferes with each of these steps. In this article, we provide an overview of the critical signaling pathways for regeneration, as revealed by investigating mammalian digit regeneration, the possible impact of aging on these pathways, and approaches to induce regeneration in the elderly. We hypothesize that with aging, increased Wnt signaling, NF-κB and tumor suppressor activity, and loss of positional information hampers regeneration. Knowledge about the impact of aging on regenerative mechanisms will enable us to safely activate endogenous regeneration in the elderly, and to generate a regeneration-permissive environment for cell therapies.