Does Malformed Lamin A Produce Enough Cellular Senescence to Contribute Meaningfully to the Progression of Aging?

Progeria is one of the better known accelerated aging conditions. It isn’t actually accelerated aging, but rather one specific runaway form of cell damage that gives rise to general dysfunction in cells throughout the body. Since degenerative aging is also a matter of general dysfunction in cells throughout the body, there is some overlap in the observed results, even though the root causes are completely different. So progeria patients appear, superficially at least, to be prematurely aged, and die from heart disease early in life.

The cause of progeria was discovered to be a mutation in the Lamin A (LMNA) gene, resulting in a malformed protein now called progerin. This protein is an important structural component of the cell nucleus. If it doesn’t function correctly, the nucleus becomes misshapen, and near all processes involving nuclear DNA maintenance and gene expression – the production of needed proteins at the right time from their genetic blueprints – cease to work correctly. The cell becomes dysfunctional. When near all cells are in this state, the prognosis for the individual is dire. Interestingly, in the years since this discovery, it has become clear that progerin is also present in small amounts in genetically normal older individuals. There is some debate over whether or not this is important in the progression of aging. Does it cause enough damage, or is it insignificant in comparison to other harmful processes?

In this context, we can consider cellular senescence, a mechanism closely connected to DNA damage, by which a small number of problem cells can cause outsized amounts of harm. Another possibility is damage to stem cells, as they are also small in number but highly influential on tissue function. Cells become senescent in response to internal damage, including that produced by progerin, and then either self-destruct or linger to secrete a potent mix of inflammatory and other signals. It is these signals, the senescence-associated secretory phenotype, that allows a comparatively small number of cells to produce comparatively large problems. It is known that senescent cells are important in many age-related conditions, particular those with a strong inflammatory component. Is generation of progerin significant as a cause of cellular senescence in normal aging, however? In this open access paper, researchers consider some of the mechanisms involved.

GATA4-dependent regulation of the secretory phenotype via MCP-1 underlies lamin A-mediated human mesenchymal stem cell aging

The LMNA gene encodes lamin and lamin C, which are major components of the nuclear lamina. Mutations in the LMNA gene have been implicated in premature aging disorders, including Hutchinson-Gilford progeria syndrome (HGPS). HGPS is caused by splicing defect and consequent generation of progerin, mutant-truncated lamin protein. Cells of HGPS patients exhibit an abnormal nuclear structure, increased DNA damage and premature senescence. In addition to the effects of progerin, accumulation of prelamin A, precursor of lamin A, induces defects in nuclear structures. ZMPSTE24 is an enzyme that produces mature lamin by cleavage of amino acids in prelamin A.

Zmpste24 knock-out mice have been widely used to study the mechanisms of aging and progeria. Depletion of Zmpste24 causes premature senescence in mice, including decreases in life span and bone density. Increased prelamin expression caused by ZMPSTE24 deficiency causes defective DNA repair. Zmpste24 knock-out mice have been extensively studied because of their impaired DNA damage response (DDR). Lamin also functions as a structural barrier to DDR. Altogether, these findings indicate that defects in the nuclear structure induced by progerin or prelamin lead to the accumulation of DNA damage, which results in accelerated aging.

It has been reported that exogenous expression of progerin in human mesenchymal stem cells (hMSCs) can impair their differentiation potential. Furthermore, production of induced pluripotent stem cells (iPSCs) from HGPS patients has revealed that the progerin expression levels are the highest in MSCs, vascular smooth muscle cells, and fibroblasts. These results indicate that MSCs are a specific target cell type of progerin-induced senescence. Like progerin, excessive accumulation of prelamin induces premature senescence in MSCs, including wrinkled nuclei. Downregulation of ZMPSTE24 in hMSCs also induces the senescence phenotype. These investigations imply that both progerin and prelamin can induce senescence in hMSCs with change in nuclear morphology.

Senescent cells secrete a group of factors that induce senescence in neighboring cells, a phenomenon termed senescence-associated secretory phenotype (SASP). The secreted inflammatory factors propagate senescence and recruit immune cells to senescent tissues by the generation of a pro-inflammatory environment. Among the factors reported to regulate the SASP, GATA4 has been recently identified as a regulator of senescence and inflammation. GATA4 is expressed during oncogene– and irradiation-induced senescence in fibroblasts in response to DNA damage. During the process of cellular senescence, GATA4 has a regulatory role in the SASP of fibroblasts. Because GATA4-dependent cellular senescence is closely associated with DDR, the role of GATA4 in other senescence models and other cell types may reveal a new mechanism.

Senescent hMSCs also induce senescence in neighboring cells. Monocyte chemoattractant protein-1 (MCP-1) secreted from senescent human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) induces premature senescence in neighboring cells. Insulin-like growth factor binding proteins are also produced by senescent hMSCs, and they trigger senescence in adjacent normal cells. These studies investigated the mechanisms of the SASP by inducing senescence in hMSCs through prolonged passaging. However, cellular senescence of MSCs can be regulated by various factors other than passaging. In our previous report, we have demonstrated that depletion of ZMPSTE24 and introduction of progerin induce premature senescence in hUCB-MSCs. It remains to be determined whether defective lamin triggers paracrine senescence via inflammatory factors in hMSCs.

In this study, we identified that paracrine senescence is triggered in senescent hMSCs with abnormal nuclear structures by increasing the expression of MCP-1 and that inhibition of MCP-1 decreases the SASP. Furthermore, we found that GATA4 mediates the senescence of hMSCs induced by defective lamin A. We assessed whether down-regulation of GATA4 disturbs the progerin- or prelamin A-dependent senescence phenotype. Elucidating how GATA4 regulates senescence in hMSCs with nuclear defects may aid in understanding the etiology of complex aging disorders. We show that inhibition of GATA4 expression protects hMSCs from cellular senescence, implying unique therapeutic opportunity against progeroid syndromes and physiological aging.


What Makes A Difference?

I’ve been dwelling with this question for a while. Like any good, real, question it is taking me for a ride. What makes a difference? Before I get into my response to this compelling question, I just want to extoll the value of a good question.  A really good question, such as this one, doesn’t […]

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Progress Towards Ways to Make Old Stem Cells More Effective for Heart Repair

Stem cells in old tissues are less active than stem cells in young tissues, meaning a lesser supply of cells to maintain the tissue, and a consequent slow loss of function. The evidence to date suggest that a sizable part of this decline is a reaction to rising levels of tissue damage and the changing balance of cell signaling that results from that damage. There is certainly damage occurring to stem cells themselves, but that doesn’t appear to contribute to as great a degree until very late in life. This means that it is feasible to think about ways to force stem cells to get back to work, to rejuvenate their behavior if not their level of intrinsic damage, and assess the benefits against the potential risks, such as a higher rate of cancer. The stem cell therapies of the past few decades suggest that this cancer risk is lower than was expected, that evolution has left us more wiggle room for therapeutic enhancement of stem cell activity in the old than it might have done.

Ischemic heart disease affects a majority of people, especially elderly patients. Recent studies have utilized autologous adult stem cells and progenitor cells as a treatment option to heal cardiac tissue after myocardial infarction. However, donor cells from aging patients are more likely to be in a senescent stage. Rejuvenation is required to reverse the damage levied by aging and promote a youthful phenotype. This review aims to discuss current strategies that are effective in rejuvenating aging cardiac stem cells and represent novel therapeutic methods to treat the aging heart.

Recent literature mainly focuses on three approaches that aim to reverse cardiac aging: genetic modification, pharmaceutical administration, and optimization of extracellular factors. In vitro genetic modification can be used to overexpress or knock down certain genes and allow for reversal of the aging phenotype. Pharmaceutical administration is another approach that allows for manipulation of signaling pathways related to cell proliferation and cell senescence. Since the stem cell niche can contribute to the age-related decline in stem cell function, rejuvenation strategies also include optimization of extracellular factors.

Overall, improving the intrinsic properties of aging stem cells as well as the surrounding environment allows these cells to adopt a phenotype similar to their younger counterparts. Recent studies show promising results of the ability of these techniques to rejuvenate the aging heart. However, more understanding of the combinatorial effects of these interventions and fine-tuning of these techniques is required to evaluate the translational potential of these methods. Each strategy has its own advantages and disadvantages. The success of myocardial regenerative treatment will require teamwork across various disciplines to make stem cell therapy a reliable method for cardiac repair.



Senescent T Cells as a Contributing Cause of Age-Related Autoimmunity

The more familiar autoimmune conditions, such as rheumatoid arthritis, are not all that age-related. Like cancer in young adults, they are a rare and unlucky happenstance, a form of most likely random cellular malfunction that spreads far enough to cause major problems. In later life, however, there occur a wide range of less familiar, less categorized, and comparatively poorly understood autoimmune conditions. It is an area of active research and many unknowns – look at just how recently type 4 diabetes was identified, for example.

These age-related autoimmunities arise from the chaotic failure of the immune system in late life. Cells fall into a variety of unhealthy states, malfunctioning cells dominate over useful cells, the immune system as a whole flails, producing chronic inflammation while failing at its primary tasks, and the supply of new competent immune cells diminishes dramatically. The publication here considers just one type of problem immune cell, those that have become senescent. This, fortunately, is an area in which solutions lie just around the corner. There is every reason to believe that senescent immune cells will just as vulnerable to destruction by senolytic therapies as any other kind of cell. If they are destroyed, they will cause no further harm, and the patient will be in a better position.

Immune aging (immunosenescence) is characterized by the reduced competence of acquired immunity, leading to increased susceptibility to infection as well as decreased vaccination efficiency. Recent accumulating evidence indicates that immunosenescence underlies an increased proinflammatory trait with age, including various chronic inflammatory and metabolic disorders, such as atherosclerosis and diabetes mellitus, as well as an increased risk for autoimmunity. Cellular senescence is characterized by irreversible arrest of proliferation, grossly altered gene expression, and relative resistance to apoptosis. Notably, senescent cells are often metabolically active and may become foci of host reactions in tissues by secreting various inflammatory factors. The features and consequences of cellular senescence in T cells in the immune system, however, remain elusive.

One of the most prominent changes occurring in the immune organs with age is an early involution of the thymus. The thymus is a central immune organ to support T cell development and establish T cell self-tolerance. T cell generation in the thymus sharply declines after the juvenile stage, eventually replaced almost entirely by fat tissues at later stages of life. In concordance with the decrease of T cell genesis, the peripheral naïve T cells are gradually reduced with age. Although the peripheral T cell pool is well maintained in aged individuals, the population shows a steady increase in the proportions of memory phenotype (MP) T cells.

We reported that a unique PD-1+ MP CD4+ T cell population is increased with age, now termed senescence-associated (SA-) T cells. The SA-T cells show characteristic signs and features of cellular senescence and emerge as follicular T cells in spontaneous germinal centers (GCs) that occur in aged mice. Spontaneous development of GCs is a hallmark of systemic autoimmune diseases, and among a number of changes in immune function with age is an increasing risk for autoimmunity.



Vascular Risk and Amyloid Level in the Brain Interact to Speed Cognitive Decline

In a recent paper, researchers provided evidence to suggest that the risk factors associated with cardiovascular decline with age interact with amyloid-β in the brain to accelerate cognitive decline. Having more of both produces a worse prognosis, which is not all that surprising. This is the case in many areas of aging and age-related disease: forms of damage and dysfunction interact with one another, making consequences worse than would be the case if they were independent of one another. This is one of the reasons why aging is an accelerating process, starting off slow and picking up pace ever more rapidly as the damage and dysfunction mounts. It is also one of the reasons why it is hard to predict the benefit resulting from any given approach to rejuvenation based on damage repair without actually trying it.

Cardiovascular risk factors such as raised blood pressure and excess fat tissue somewhat measure and somewhat predict the pace at which the complex machinery of blood vessels ages. In particular the failure of smooth muscle in blood vessel walls to correctly react to circumstances with dilation and contraction, the loss of capillaries delivering nutrients to energy-hungry tissues like the brain, and the progression of atherosclerosis, weakening and narrowing blood vessels with fatty plaques. There are other important processes, however, such as the routes for drainage of cerebrospinal fluid, or other ways in which amyloid-β and other metabolic waste might exit the brain.

Past research has shown that there is an equilibrium of sorts between amyloid-β in the brain and amyloid-β in the vascular system outside the brain. It is possible to drain amyloid-β from the brain to some degree by reducing it elsewhere in the body, indicating that there are processes transporting amyloid-β into the blood system, in addition to those removing it via other paths of cerebrospinal fluid drainage. This likely involves the blood-brain barrier, a part of blood vessel walls where they pass through the central nervous system, and thus is impacted by the state of vascular aging and dysfunction. This is the sort of thing one would look into if searching for the mechanisms underlying the relationship noted in the research below.

Vascular risk factors interact with amyloid-beta levels to increase age-related cognitive decline

Alzheimer’s disease and cerebrovascular disease are probably the two most common causes of cognitive impairment in the elderly, but even though they often co-occur in individual patients, they are typically viewed as independent contributors. While the presence of amyloid plaques in the brain is considered a hallmark of Alzheimer’s disease, some individuals with elevated amyloid levels never develop cognitive impairment. This has led to a search for additional markers beyond brain amyloid to help identify those at increased risk for cognitive decline.

The current study was designed to investigate whether the effects of increased brain amyloid and of vascular risk on cognitive decline are merely additive, reflecting a simple combination of the risks independently contributed by each factor, or synergistic, in which interaction of the two produces an even higher level of risk. The study analyzed data from 223 participants in the Harvard Aging Brain Study, an ongoing study of cognitively normal individuals ages 50 to 90 designed to improve understanding of brain changes affecting memory and cognition that occur with aging.

Upon enrollment in the study, participants receive standard imaging biomarker studies, including PET scans with a compound that reveals amyloid deposits in the brain. Assessment of vascular risk is determined by the Framingham cardiovascular risk score, which is based on factors such as hypertension, body mass index, and histories of diabetes or smoking. Participants also receive standard tests of memory, attention and language, which are repeated at annual follow-up visits.

The results showed that both elevated brain amyloid levels and higher vascular risk, as measured upon study enrollment, were associated with more rapid cognitive decline, with the most rapid changes seen in participants with elevations in both factors. The extent of the interaction between the two measures suggested a synergistic, rather than simply an additive effect.

Vascular risk factors interact with amyloid-beta levels to increase age-related cognitive decline

Identifying asymptomatic individuals at high risk of impending cognitive decline because of Alzheimer disease (AD) is crucial to the success of clinical trials aimed at preventing dementia. The advent of in vivo measures of β-amyloid (Aβ) burden highlighted a preclinical phase of AD allowing for the identification of clinically normal individuals with objective evidence of AD pathology. However, a substantial portion of individuals who are amyloid positive do not show clear evidence of cognitive decline in available longitudinal follow-up data. This is consistent with autopsy data indicating that approximately 30% of clinically normal elderly individuals have signs of elevated Aβ burden on pathological examination. These findings have prompted the search for additional biomarkers that can be used with Aβ burden to identify individuals at maximal risk of cognitive decline.

Multiple studies have demonstrated that cardiovascular risk factors, such as hypertension and hyperlipidemia (which often occur together), are also risk factors for cognitive decline and AD. Consistent with this, recent epidemiological data suggest that declining dementia incidence may be partially because of advances in the treatment of cardiovascular disease. Neuropathological studies indicate that vascular brain changes frequently co-occur with AD pathology in late-onset dementia and that vascular pathology may lower the threshold for cognitive impairment.

The goal of the present study was to examine whether a well-validated, multivariable measure of vascular risk is associated with prospective cognitive decline in a large cohort of clinically normal elderly individuals, either additively or synergistically with Aβ burden.


Financial Consumers, Beware: “All Financial Advice Comes with Conflicts of Interest” says MarketWatch

When it comes to getting good, unbiased financial advice, do you know where to turn? And are you confident that the fees you’re paying justify the service your financial planner is providing for you? It turns out, based on this recent column we read on MarketWatch, that even savvy investors can find themselves paying exorbitant fees for bad advice – advice that can cost them thousands in unnecessary taxes and substandard returns on their investments. Even for the majority of us with relatively modest-sized retirement portfolios, this column, written by retirement expert and author Chris Mamula, sounds an important alarm, warning us against trusting our financial adviser too blindly.

Personal Experience

“I began writing about personal finance to create a positive outlet for the anger, regret, and pain I experienced because of investing mistakes I made as a young professional,” Mamula begins his column. As he explains, he became a consumer advocate “to help others avoid repeating my mistakes” – errors which, he explains, “were the result of blindly following the advice of a financial adviser without performing due diligence.” By Mamula’s estimation, the self-serving advice of his adviser ended up costing thousands in unnecessary fees and taxes. “Compound the effects of these mistakes over decades,” he writes ruefully, “and this was literally a million-dollar mistake.”

Are all financial advisers bad people who are out to fleece their clients? Of course not, and that’s not what Mamula in his MarketWatch article is saying. Here at AgingOptions we agree that many men and women in the field of financial counseling and investment services perform an invaluable function every day for their clients who rely on their honesty, advice and expertise. The problem, Mamula suggests, is that there are a limited number of ways for financial advisers to earn a living, and in virtually every scenario, there are potential conflicts of interest in which the benefit to the adviser and the benefit to the client of any financial strategy or purchase clash. “I strongly recommend that you understand that financial advice comes with inherent conflicts of interest,” writes Mamula. “As a consumer, you must understand what these conflicts are, so you can make good decisions and protect your interests.”

Three Types of Compensation

The article provides a helpful overview of how financial advisers and planners are paid. “There are essentially three models to compensate advisers, says Mamula in MarketWatch. “You can pay for financial advice through commissions on products you buy. You can pay as a percentage of assets under management. Or you can pay a direct fee for financial advice. Each comes with unique upsides, downsides and conflicts.”

  • Commissions: Here the adviser receives a sales commission on the financial products you buy. Mamula says that for most middle-income clients, commission-based financial advice is the most common. However, he adds, “The conflicts of interest are obvious. A financial adviser paid by commissions is really a salesman of investment products.” That means you have no way of knowing if the adviser is basing his or her financial recommendation on what’s best for you or on which firm pays the biggest bonus.
  • Assets Under Management: In this common model the financial planner is paid a percentage based on the amount of your money he or she is managing. Proponents claim this model eliminates conflicts of interest: “Because advisers are paid a percentage of the wealth you accumulate,” says Mamula, “they claim an adviser’s interests are aligned with the investor’s, because both a client and adviser benefit when wealth grows.” But, he adds, “I disagree.” The problem here is that advisers are paid to keep your money under their management, not necessarily to advise you objectively. What if your funds might be better invested elsewhere? “There is incentive [under this model] for the adviser not to rock the boat. Remember, they get paid for having assets under management, not for giving good advice.”
  • Fee Only: “The third model,” says Mamula in MarketWatch, “is paying a fee only for advice you receive. This is the most transparent model” because you are paying pre-determined fees directly to the planner. While you might think that the fee method of compensation eliminates most conflicts of interest, it’s not a perfect system, because advisers don’t earn as much if they keep things simple. “The problem with paying for investing advice is the incentive it creates to make things complicated,” Mamula warns. “Unnecessary complexity is common in the financial industry. Making investing complex is a way for the financial industry to justify their existence” by forcing clients to rely on them to keep everything straight.

Compensation Can Mean Conflict

The point, Mamula reminds us, is to assume that all financial advice comes with inherent conflicts of interest. “If you plan to seek investment help, you need to understand how your financial adviser is paid and the conflicts this can create. Go in with your eyes wide open or your vision may soon be further obscured when storm clouds start forming.”

Here at AgingOptions, we think this is sound advice, but we would take it a step farther.  As Rajiv Nagaich puts it, there’s a big difference between the process of getting good advice and the process of implementing that advice. “Advice, especially financial advice, should be about getting to the how-to answers,” Nagaich says. “Then, once your strategy is clear, you can seek out the least expensive options to put that strategy to work.” By employing low-cost, low-frills firms like Vanguard or Charles Schwab, even a relatively inexperienced investor can put his or her retirement funds to work without incurring the burden of unnecessary fees, commissions and taxes. “There’s no need to pay a so-called professional for financial transactions most average retirees can manage for themselves,” Rajiv suggests.

Much More Than Money

If there’s one area where good, comprehensive advice is absolutely necessary, it’s in the area if retirement planning, where there’s far more at stake than simply worrying about money. You also need to protect yourself and your estate legally and medically. You need to prepare carefully for your present and future housing needs. You need to ensure that your family is aware of your desires and will support their implementation. The only way we know of to build a plan that encompasses all these facets is with a LifePlan from AgingOptions. A LifePlan truly becomes your road map to fruitfulness and security in all aspects of your retirement future.

We invite you to come join Rajiv Nagaich at one of our free LifePlanning Seminars. Do what thousands have done and invest just a few hours with Rajiv, and we assure you, you’ll never look at retirement planning the same way again. For a complete listing of currently-scheduled seminars, visit our Live Events page. We’ll look forward to meeting you soon at an AgingOptions LifePlanning Seminar with Rajiv Nagaich.

(originally reported at

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Bleak Assessment: is the Pharmaceutical Industry “Giving Up” on Finding an Alzheimer’s Cure?

Here in America we like to think the smart men and women in their lab coats, working in their well-equipped research labs, can tackle pretty much everything when it comes to our medical problems. After all, it seems to work that way in the movies! But this is real life, and while we love to celebrate the great strides medical science continues to make in preventing (and one day curing) deadly diseases like heart ailments and many types of cancer, the most frightening disease of all still remains stubbornly resistant to our scientific efforts. We just don’t seem any closer to a medical treatment for Alzheimer’s disease.

That appears to be the conclusion from this sobering column that was just published on the Quartz website. Written by Quartz reporter Katherine Ellen Foley, this article is called, “Why the pharmaceutical industry is giving up the search for an Alzheimer’s cure.” Indeed, as Foley writes, there have been a series of recent clinical trials that have failed or otherwise proved disappointing in addressing the relentless progression of Alzheimer’s disease, the dementia that afflicts well over 5 million Americans. “This year,” Foley writes, “the total cost of caring for all of the people in the US with this disease is expected to reach $1 trillion—higher than it’s ever been before. And yet despite what has obviously become a crisis, there hasn’t been a new treatment for Alzheimer’s in over a decade.”

Frustration and Failure

Foley reports that, while there are some psychiatric drugs that may help dementia patients deal with their anxiety, there are still no drugs that do a good job of slowing memory loss, and the most recent of those to be approved – sold as Namenda – is 15 years old. During the past decade and a half, a Who’s Who of pharmaceutical giants have tried and failed to get new dementia drugs successfully through clinical trials: Eli Lilly, Axovant, Merck, Biogen, and Prana Biotech. Biomed colossus Pfizer, after facing a round of clinical setbacks, announced its decision last January to “drop out of the Alzheimer’s drug game entirely,” Foley writes.

What makes Alzheimer’s disease so fiendishly hard to attack? Writing in Quartz, Foley says that this type of dementia poses three enormous challenges for researchers. First, the disease typically shows no symptoms at all for years, even decades, and by the time symptoms manifest themselves the brain is already too damaged to treat. Second, there are presently “no good methods to tell if someone has the early, biological stages of the disease,” writes Foley. “At the moment, the only definitive diagnostic tools for Alzheimer’s detection are costly or painful” – so much so that they can’t be used for general screening.   This leads in turn to the third problem, which involves the difficulty of recruiting the right patients for clinical trials. “Healthy people,” says Foley, “have no incentive to enroll in these types of drug studies, and there’s no good way to identify people with risk for the disease, or even initial biological signs of the disease.” The result is a stalemate: “In essence, scientists currently have no way to study Alzheimer’s patients for long enough to test memory-loss prevention drugs.”

Focus on Early Detection

The Quartz article goes into long and interesting detail about the history of this little understood disease, and also about funding for Alzheimer’s research which got a huge shot in the arm when the Obama administration made it a national goal (with funding to match) to find a cure by 2025. But in spite of research spending which hit $1.4 billion in 2017 (and which will decline to about $837 million in 2018 according to the National Institutes of Health), there hasn’t been much progress on the drug front. That’s why researchers are starting to focus more closely on the challenge of early diagnosis. “In theory,” the Quartz article says, “the best way to treat Alzheimer’s disease would be to stop the brain-cell destruction before it starts. The problem is that during the earliest stages of Alzheimer’s, people have no way of knowing that anything is wrong.”  Doctors are working to come up with blood tests or PET scans that can detect the presence of the plaque accumulations that are common inside the brains of those in dementia’s early stages. This approach is still in its infancy.

What about research into lifestyle changes – diet, exercise, socialization? This, too, appears promising, writes Foley (the National Academy of Sciences called one such report “inconclusive but encouraging”). As the Quartz analysis points out, though, it’s unlikely that big research dollars will flow into some of these non-pharmaceutical approaches. “Pharmaceutical companies still have the deepest pockets,” the article states. Even though clinical drug trials are terribly expensive, future drug sales typically make up for the up-front investment. Not so with lifestyle recommendations. “You can’t patent exercise or salmon-rich diets,” writes Foley. “Without the promise of a big payoff, it’s doubtful pharmaceutical companies will fund studies to explore whether and how these lifestyle interventions work.”

Plan for Any Eventuality

So what’s our advice here at AgingOptions? Is the picture all doom and gloom? Absolutely not. While a scientific breakthrough is always a possibility, the lifestyle changes most physicians advocate can only improve your quality of life, often without costing you an extra cent. But here’s our essential take-away: families simply have to do a better, more thorough job of planning for the future. This includes financial planning so you don’t run out of money. It includes planning your housing choices, so you can age in place as long as possible. You need to protect yourself legally so your wishes are honored. You need to prepare your medical plans both for the short term and long term. And on top of all that your family members – who may very likely become your primary caregivers – have got to be on the same page and know what will be expected of them. In short, you need an AgingOptions LifePlan, the only type of comprehensive retirement plan that helps you protect your assets, avoid becoming a burden to those you love, and escape the trap of unwanted and unplanned institutional care.

We urge you to bring your spouse and adult kids and join Rajiv Nagaich soon at an AgingOptions LifePlanning Seminar so you can learn more. This could absolutely be the most important investment of a few hours of your time that you will ever make! Visit our Live Events page where you’ll find dates, times and locations of upcoming seminars – then register online for the event of your choice or call us for assistance. You’ll discover peace of mind like you ever thought possible, once you embrace the protective power of an AgingOptions LifePlan.

(originally reported at

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If You’re Facing Divorce, Make Sure Your Rights to Retirement Savings are Protected

We were reading financial columnist Michelle Singletary’s latest column in the Washington Post a few days ago when something in the article really grabbed our attention. It wasn’t the column itself, which was about “401(k) millionaires” – instead it was a reader comment buried far down in the Singletary column that set off warning bells. We felt this information needed to be shared with our AgingOptions blog readers.

An Unexpected Shock

A reader wrote to Singletary reporting that her husband had retired from the federal government some time ago. He had begun receiving estimated pension payments while the personnel office took their customary period of time (typically several months) to check the records and work out the details. Four months after his retirement, much to his shock, he received a letter from the federal Office of Personnel Management notifying him that henceforth half of his retirement pay and all of his retirement survivor benefits would be going to his ex-wife. Apparently, this gent had never read his divorce agreement which clearly stated what his ex would receive once his retirement date rolled around.

Fortunately, this case had a happy ending: the ex-wife had just started receiving her partial payments – completely unexpectedly – but as it happened, she was planning to remarry and wanted no part of the man’s benefits. The personnel office was able to get the situation settled in favor of spouse number two after an attorney successfully drafted documents reversing the original divorce agreement. But this does bring up a vital question: is there a way for divorcing spouses to protect each of their rights when it comes to divvying up retirement assets such as 401(k) balances, which these days are often among the largest assets a couple approaching retirement age owns?

Protecting Your Rights in a Divorce

At AgingOptions, our attorneys deal with this issue frequently. In searching for an article we could share with our readers that would answer the question, we found this insightful column on a website called The Balance, an article that appeared just a few months ago. “Even while you’re going through the difficulty of a divorce,” this article advises, “you need to make informed financial decisions regarding the division of the property that you and your spouse have accumulated during your marriage.” Because retirement savings, as we said above, are often a couples’ biggest asset, dealing properly with their disposition is vitally important. Sadly, however, this is often done improperly – or not at all. “Even as one of the most important issues, [retirement savings] also tend to be very complicated, subject to tax implications, and often not handled properly because of it,” says The Balance. The solution, this article says, is something called a QDRO, pronounced “Quadro” – a Qualified Domestic Relations Order.

Legally, if you or your spouse has an employer-sponsored retirement plan, you’re entitled to part of the balance. The converse is also true: if you’re the one with the retirement account, your spouse is legally entitled to a share. “But if your spouse was the primary breadwinner,” asks the column in The Balance, “how do you protect your share of his or her retirement account? What’s to stop your spouse’s employer from paying out the benefits to your spouse or ex-spouse, leaving you with little or nothing? The answer is generally a Qualified Domestic Relations Order.”  The QDRO is a court order that tells your spouse’s pension plan how your benefits will be paid out. Under such an order, for example, your share of the 401(k) can be separated out from the original account and deposited into your own IRA or 401(k) without penalty. The word “qualified” means the plan has to be approved both by the divorce court and by the Plan Administrator where you or your soon-to-be-ex-spouse is employed.

Preparation Requires Education

We won’t attempt to go into greater detail here, because the variables involved in a Qualified Domestic Relations Order can quickly get complicated. This is clearly one area where you need to plan ahead and get good legal counsel before proceeding with a divorce. As the column in The Balance says, “Divorce can be costly be in terms of upfront attorney fees and emotional health. But it can also have costly effects on your future financial security. Educating yourself is the first step. But be sure to take the appropriate legal steps to protect your rights and always employ a qualified team to help you do so.” We here at AgingOptions can certainly advise you in this critical area, and through our many regional offices of LifePoint Law, we can serve as your advocate should you prefer. Please contact us and allow us to walk you through the various scenarios in the often-confusing area of dividing assets – both today’s assets and tomorrow’s – in a divorce or separation.

When it comes to walking you through the various scenarios of retirement, that’s a particular specialty of ours. Retirement can also be confusing and complicated, but our desire is to help you make these important retirement planning decisions more manageable so that you can achieve the three most commonly-stated goals people have as they age: to avoid running out of money, to avoid becoming a burden to those who love them, and to avoid unplanned and unwanted institutional care. If these goals are so commonly, why do so few retirees ever succeed in realizing them? Because they fail to plan.

To protect your interests, we employ a strategy called LifePlanning, in which your finances, legal affairs, housing options, medical coverage and family communications are all woven together seamlessly, each element reinforcing the others. A LifePlan truly is the blueprint that will help you build the retirement of your dreams. Ready to learn more, without obligation or cost? Then come join Rajiv Nagaich soon at an AgingOptions LifePlanning Seminar. We have several scheduled for the coming weeks, and there’s bound to be one that’s convenient for you. Visit our Live Events page for details and online registration, or contact us for assistance. We’ll look forward to meeting you!

(originally reported at

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Two Senators Join Forces Across the Aisle to Push for a “Retirement Crisis Commission”

These days it seems like Democrats and Republicans seldom agree on anything. So it makes the news when two prominent Senators, one a conservative from the GOP and the other a progressive Democrat, come together to advocate publicly for a top-level federal commission to address what they call a retirement crisis in America.

We discovered this article last week on the website NextAvenue. The article, penned by so-called “unretirement expert” Chris Farrell, spotlights the recent bipartisan legislation put forth by New Jersey Democrat Cory Booker and Indiana Republican Todd Young calling on the government to take urgent action to deal with a retirement system in the U.S. that has been labeled “a huge, huge mess” by analysts. Senators Young and Booker want Congress to form a blue-ribbon commission, dubbed by author Farrell the Retirement Crisis Commission, to propose new laws that would protect a huge swath of America’s workers who presently have zero access to employee sponsored retirement savings plans.

40 Years in the Making

Ironically, in spite of all the changes and economic shifts in recent decades, the last time the government took a long and careful look at private sector retirement rules was during the Gerald Ford administration, when the then-President signed into law the Employee Retirement Income Security Act (ERISA), offering federal protection for private pension plans. (The ERISA law had been triggered in part by the bankruptcy of Studebaker a decade before.)

Senators Young and Booker say we’re due for another government initiative. “My hope is that the commission would deliver to Congress some ideas that are bold and ambitious,” says Senator Young, quoted in the NextAvenue article. “It has been 40 years since Congress has looked at private retirement security in a comprehensive manner. In the intervening decades the economy has been transformed” – with many millions of American workers left behind.

The problem, say experts, is that the disjointed retirement system in the U.S. “has evolved (devolved, really) into an overly complex, byzantine and woefully inadequate safety net for America’s retirees,” Chris Farrell writes. The inadequacy of the American approach to retirement legislation is shown in multiple ways. “About 40 percent of full-time private-sector employees lack access to an employer-sponsored retirement savings plan,” says Farrell, referring mostly to workers at small-to medium-sized businesses with no retirement savings programs. On top of those millions, we have an army of freelancers, independent contractors and gig economy workers who can’t participate in an employer-sponsored retirement plan because they’re not technically employees. (Most part-time workers are in the same boat.) What’s more, just because a worker has a plan doesn’t mean it’s doing its job. “Even people who can sign up a 401(k) retirement plan at work often find it hard to save and manage their portfolio,” says the NextAvenue article, which helps explain the “dismal” figures on how much workers are actually saving in their plans.

What’s the Point?

In light of the poor track record of past blue-ribbon commissions, the obvious question becomes, “What is this Retirement Crisis Commission supposed to do?” Senators Young and Booker have big ideas. First, the make-up of the commission would ensure top-level attention: they want it to include the U.S. Secretaries of Labor, Treasury and Commerce; two presidential appointments; six appointees from the U.S. Senate and six from the U.S. House of Representatives. This group of heavyweights would focus exclusively on private sector plans, not on Social Security. The critical questions are, first, what’s it going to take to help Americans save more for retirement; and, second, how do you cover the huge number of today’s workers with no access to a retirement savings plan?

There are plenty of options to consider, says Senator Young, including some that have been proven in other nations. Australia and some Scandinavian countries, for instance, have enacted mandatory retirement savings programs which are working well. All these various options are well and good, says the NextAvenue article, but even the strongest recommendations may end up stillborn without bipartisan support at the highest levels of government. “Even if Congress approves a retirement commission, the risk is that its report will get shelved,” says the article. “That’s what happened to the retirement system study launched in 1979 by President Carter. Its recommendations — including a mandatory universal private pension — were released in 1981” – just in time for a new administration with a different set of national priorities to kill it.

No Time to Waste

If your idea of retirement planning involves waiting for the government to do the right thing, you may have a long wait. Instead, it’s time to take charge of your retirement by doing some comprehensive and in-depth planning of your own. Here at AgingOptions we call this “LifePlanning,” because it really does take into account the full spectrum of your life in retirement, including your financial preparation, your legal protection, your medical coverage, your housing plans and your family communications. With a LifePlan in place, no matter what the circumstances, you’ll be able to protect your assets in retirement, avoid becoming a burden to those you love, and escape the trap of unwanted, unplanned institutionalization.

There’s an easy, no-risk next step to learn more about the power of LifePlanning. Make a commitment now to join Rajiv Nagaich soon at an upcoming LifePlanning Seminar, where you’ll gain valuable insight into this revolutionary approach to retirement planning. For details and upcoming dates and locations, visit our Live Events page by clicking here: then register online for the seminar of your choice or call us for further information.

Trusting Uncle Sam with your retirement planning is a recipe for disaster. Instead, trust the objective professionals at AgingOptions. We’re ready to be your partner and guide as you build the retirement of your dreams. Age on!


(originally reported at

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Are Mitochondria at the Root of Age-Related Loss of Muscle Mass and Strength?

Sarcopenia, the age-related loss of muscle mass and strength, has many possible contributing causes. There is fair evidence for most of them, from a failure to process amino acids needed for construction of new muscle mass to damaged neuromuscular junctions to loss of stem cell function. The most compelling evidence I’ve seem points to that stem cell dysfunction as the most significant contribution. It is certainly the case that stem cell populations decline in size and activity with age, reducing the supply of daughter cells needed to maintain tissues in good condition. Muscle stem cells are among the most studied in aging research.

The paper noted here picks through the major themes in sarcopenia, and makes the argument for linking at least some of them to age-related issues in mitochondrial function. The mitochondria are the power plants of the cell, and muscle is an energy-hungry tissue. Mitochondria can suffer forms of damage that make them harmful to their cells and the surrounding tissue; this is a significant issue in aging. More generally, all mitochondria change for the worse in old tissues, possibly in reaction to other forms of molecular damage characteristic to old tissues. They alter in shape and dynamics, and their ability to generate the energy store molecules required for cellular operations declines. How much of sarcopenia can be explained by these phenomena? Some, I think, possibly not all.

Using a targeted metabolomics approach, participants with low muscle quality presented significantly higher plasma concentrations of isoleucine and leucine, suggesting that low muscle quality is characterized by impaired transport of amino acids, especially branched chain amino acids (BCAAs), across the muscle cell membrane. The exact reasons for why amino acid uptake is reduced in older persons with low muscle quality are unknown, and further work is required to identify putative intervention/therapeutic targets.

Physiologically, amino acid uptake in muscle cells is regulated by three fundamental mechanisms: insulin signalling, BCAA (primarily leucine) blood concentration, and physical activity. Previous studies have also suggested that these ‘anabolic‘ signals cause increased amino acid entry by dynamically enhancing muscle perfusion, and all three signals exhibit a dose-response relationship that is steeper in younger than in older persons. In other words, older persons tend to develop an ‘anabolic resistance’ to the three stimuli. Since muscle perfusion adaptation is mediated by endothelial reactivity, which is hampered by a pro-inflammatory state, this hypothesis can also explain why inflammation is such a strong correlate and predictor of age-related sarcopenia.

During ageing, mitochondria lose the ability to produce energy during maximal efforts but not when the energetic demand is lower. This impaired mitochondrial function could be due to inadequate perfusion or reduced muscle blood flow, resulting in lower oxygen delivery in skeletal muscle and diminished aerobic capacity. This hypothesis is interesting because it connects both energetic and anabolic deficits to the same mechanism. These results indicate that oxidative phosphorylation is progressively impaired with ageing; it is unclear whether this is because the number of mitochondria per muscle volume is diminished, the intrinsic capacity of mitochondria to generate ATP is impaired, or the availability of oxygen and nutrients at different levels of effort is compromised.

Oxidative stress and defective mitophagy (mitochondrial autophagy) are potentially involved in the decline of muscle quality with ageing and need to be considered. Dysfunctional mitochondria are characterized by reduced oxidative phosphorylation efficiency and excessive production of reactive oxygen species, which oxidize and damage macromolecules. The hypothesis that oxidative stress causes degenerative changes in tissues that are highly metabolically active, such as the brain and the muscle, has been proposed for many years. Oxidative stress may also affect satellite cells or muscle stem cell pools in skeletal muscle.

Defective mitochondrial function has been studied in regard to the neuromuscular junction (NMJ) remodelling that occurs with ageing, producing cycles of denervationinnervation that lead to motor unit loss, specifically in type II fibres, as well as muscle fibre atrophy. However, it is not clear whether these changes in the NMJ precede or follow the observed decline in muscle mass and strength that is observed with ageing. Some studies have reported altered mitochondria morphology in the NMJ that produce increased levels of oxidative stress, decreased enzymatic activity and ATP production, and impaired calcium buffering. The combination of these biological changes may have a strong negative impact on excitation-contraction coupling and eventually lead to the loss of motor units.

Overall, low muscle quality seems to be associated with (i) metabolic impairments that lead to reduced incorporation of the three major BCAAs, which are used by muscle as energy sources and are associated with muscle strength and endurance; (ii) fat accumulation in muscle tissue that ultimately leads to architectural disruption and loss of function; and (iii) high concentration of lipid species that are associated with impaired mitochondrial function and unrecycled mitochondrial proteins, potentially due to defective mitophagy or proteostasis. The extent and complexity to which these mechanisms are interconnected is unknown and should be examined in future studies. In addition, other factors that impact ageing muscle could also modulate mitochondrial function, such as (i) defects in the NMJ that leads to myofiber denervation-due to reduced capacity in motor neurons to reinnervate muscle fibres-consequently causing fibres to become atrophied; (ii) the age-associated decline in the satellite cell pool, reducing muscle regeneration after injury; and (iii) ‘inflammaging‘, the chronic low-grade inflammation observed in older persons.