Frailty & Muscle Loss Increase Mortality & Are Common in HIV+

Subject: NATAP/CROI: Frailty/Muscle Loss in HIV Increases Mortality & is Common

NATAP http://natap.org/
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Frailty & Muscle Loss Increase Mortality & Are Common in HIV+

from Jules Levin at CROI Live in Seattle. This poster session is a
breakthrough in that it is identifying that muscle loss & frailty are
fairly common in HIV+ persons & they increase mortality. AND HCV & HBV
contribute to frailty in one study below.read this:

"Frailty is a significant predictor of mortality among both HIV+ and
at-risk IDU....... Impaired functional capacity is strongly associated
with lower bone density and lower muscle mass in middle-aged HIV-1+
persons......Co-morbidity Is Predictive of Muscle Strength in HIV+
Veterans: Results from the VACS Index....
Overall, 40% of SUN study participants aged ≤50 years with
well-controlled HIV infection were pre-frail or frail. The significant
association of pre-frailty and frailty with a history of opportunistic
infection suggests earlier diagnosis of HIV infection and prevention of
opportunistic infections may reduce risk for frailty.......Prevalence
of low muscle mass increases with age. The highest prevalence was found
in the 41- to 50-year age group. Predictors of FFMi change appear to be
associated with age, lipoatrophy recovery, and time. FFMi is associated
with all-cause mortality in HIV+ patients, suggesting that this
biological entity can provide prognostic information, in HIV+
patients..........We have recently demonstrated that patients with
prior exposure to nucleoside analog ARV, which inhibit DNA
polymerase-γ, accumulate acquired mitochondrial DNA (mtDNA) mutations
in skeletal muscle, in an apparent acceleration of the process seen in
normal aging. Here we explore an in vivo functional correlate in aging
HIV+ patients. Abnormalities of resting muscle pH handling have been
associated with fatigue and may contribute to functional decline in
this patient group."



Frailty and Pre-frailty in a Contemporary Cohort of HIV+ Adults

Nur Onen*1, P Patel2, J Baker3, L Conley2, J Brooks2, T Bush2, M
Kojic4, J Hammer5, E Overton6, and SUN Study Investigators

1Washington Univ Sch of Med in St Louis, MO, US; 2CDC, Atlanta, GA, US;
3Hennepin County Med Ctr, Univ of Minnesota, Minneapolis, US; 4Miriam
Hosp, Providence, RI, US; 5Denver Infectious Disease Consultants, CO,
US; and 6Univ of Alabama at Birmingham, US

Background:  HIV+ persons can become prematurely pre-frail and frail;
however, pre-frailty prevalence and risk factors for both frail and
pre-frail states have not been fully elucidated.

Methods:  Using data from a contemporary prospective observational
cohort of HIV+ adults (SUN Study), we determined the percentages of
non-frail, pre-frail, and frail participants at the most recent study
visit by the respective presence of 0, 1 to 2, and ≥3 of 5 established
frailty criteria as shown in the table. We evaluated associations with
pre-frailty/frailty using logistic regression analysis.

Results:  Of 308 SUN Study participants assessed—79% men, 58%
non-Hispanic white, median age 47 years (interquartile range 41 to 53),
95% on combination ART, median CD4 cell count 650 cells/mm3 (IQR 467 to
799), and 93% HIV RNA <400 copies/mL—57% were non-frail, 38% pre-frail,
and 5% frail (61%, 36%, and 4%, respectively, among the 199 [65%]
participants aged ≤50 years). Prevalence of frailty criteria are
presented in the table; exhaustion and physical inactivity
predominated. In multivariate analysis, pre-frail/frail vs non-frail
participants were more likely of non-white race/ethnicity (54% vs 33%;
adjusted odds ratio 3.24; 95% confidence interval 1.78 to 5.91), to
have had an AIDS-defining opportunistic infection (35% vs 15%; aOR
2.55, 95%CI 1.29 to 5.02), to have poorer median perceived health
scores on the SF-12 health survey (1, IQR 1 to 2 vs 2, IQR 1 to 3; aOR
2.12, 95%CI 1.49 to 3.03), to have higher median PHQ-9 depression
scores (6, IQR 2 to 11 vs 3, IQR 0 to 5; aOR 1.11, 95%CI 1.04 to 1.18)
and to be older (median age 48 years, IQR 44 to 54 vs 46 years, IQR 40
to 52; aOR 1.04, 95%CI 1.01 to 1.07). Lower CD4 cell count nadir,
female sex, and unemployment were not independently associated with
pre-frailty/frailty.

Conclusions:  Overall, 40% of SUN study participants aged ≤50 years
with well-controlled HIV infection were pre-frail or frail. The
significant association of pre-frailty and frailty with a history of
opportunistic infection suggests earlier diagnosis of HIV infection and
prevention of opportunistic infections may reduce risk for frailty.
Racial disparities warrant further investigation.
-------------------

Low Muscle Mass in HIV+ Patients: Prevalence, Predictors, and Clinical
Implication

Giovanni Guaraldi*1, S Zona1, A Silva2, G Orlando1, F Carli1, A
Santoro1, N Crupi2, G Ligabue1, C Mussi1, and L Ferruci3

1Univ of Modena and Reggio Emilia, Italy; 2Hosp de Joaquim Urbano,
Porto, Portugal; and 3Natl Inst on Aging, NIH, Baltimore, MD, US

Background:  In HIV+ patients, muscle mass measured as fat free mass
index (FFMi = FFM/h2) in DXA has never been characterized in large
epidemiological cohorts. We aimed:  to describe the prevalence of low
muscle mass using t- and z-score, per age decades, defined as <–2 SD
from the mean FFMi for an Italian Caucasian population, respectively,
for the same age or in the age strata 30 to 39 years; to identify
predictors of FFMi change; and to assess the association between FFMi
and all-cause mortality in a large HIV+ cohort.

Methods:  This observational prospective study included all consecutive
patients from 2005 to 2011 who underwent at least 2 DXA scans,
performed 1 year apart. Univariate and multivariable longitudinal
linear regressions were built to evaluate FFMI change-associated
factors. Co-variates included in the models were:  age, sex, body mass
index (BMI), physical activity; change in leg fat percentage (assessed
with DXA), in visceral adipose tissue (VAT), and in total adipose
tissue of the abdomen (TAT) (assessed with abdominal CT); NRTI, NNRTI,
and PI cumulative exposure; CD4 nadir and recovery; vitamin D plasma
level; and time between DXA scans. A Cox model was built to predict the
impact of FFMi on all cause mortality after adjustment for age and sex.

Results:  A total of 1696 HIV+ patients (1046 men) were analyzed.
Median observation follow-up period was 3.5 years (IQR 2 to 5); 96% of
patients were on ART, and during the follow-up period 37 died. BMI
change and FFMI change appeared stable over time (ß = 0.001, p = 0.111;
ß = 0.001, p = 0.070, respectively). In men, the prevalence of low
muscle mass using t- and z-scores was 0.2% and 8.5%, respectively. In
women, the prevalence of low muscle mass using t- and z-scores was 0%
and 1.5%, respectively. The highest prevalence of low muscle mass was
detected in the 41- to 50-year age group strata (t-score 0.5% and
z-score 16%). Predictors of FFMi change were:  age (ß = –0.01, p =
0.002), change of leg fat percentage (as a surrogate for lipoatrophy
recovery) (ß = –0.05, p <0.001), and time between DXA scans (ß = 0.17,
p = 0.013). FFMi was associated with all-cause mortality (HR 0.87,
95%CI 0.78 to 0.98) after adjustment for age and sex.

Conclusions:  Prevalence of low muscle mass increases with age. The
highest prevalence was found in the 41- to 50-year age group.
Predictors of FFMi change appear to be associated with age, lipoatrophy
recovery, and time. FFMi is associated with all-cause mortality in HIV+
patients, suggesting that this biological entity can provide prognostic
information, in HIV+ patients.
---------------------

Frailty Predicts Mortality in a Cohort of HIV+ and At-risk IDU

Damani Piggott*, A Muzaale, S Mehta, T Brown, S Leng, and G Kirk

Johns Hopkins Univ, Baltimore, MD, US

Background:  Frailty, a syndrome of diminished physiologic reserve with
increased stressor vulnerability, predicts hospitalization, disability,
and mortality in older HIV– adults. We have previously observed a
significant association between frailty and HIV+, particularly advanced
HIV infection, among injection drug users (IDU). In this study, we
evaluated the impact of frailty on mortality in a cohort of aging HIV+
and at-risk IDU.

Methods:  Frailty was assessed biannually from 2005 to 2008 among
current and former IDU in the ALIVE cohorts and was defined by the
presence of ≥3 of 5 standard criteria:  weakness (grip strength), slow
gait speed, weight loss, low physical activity, and exhaustion. Cox
proportional hazards models with time-varying co-variates were used to
estimate the risk (hazard ratios with 95% confidence intervals) for
all-cause mortality among frail persons relative to their robust
counterparts (defined by the absence of any criteria) and to non-frail
persons.

Results:  For 1230 subjects at baseline, the median age was 48 years,
89% were African American, 418 (34%) were female, and 351 (29%) were
HIV+. The prevalence of frailty was 9%, while 31% met no frailty
criteria. In Cox multivariable analysis of 3365 person-visits,
increasing age and HIV status were associated with increased mortality
risk. Adjusting for age, race/ethnicity, gender, educational level, and
HIV status, frail persons had a 3.4-fold increased risk of death
relative to robust persons (HR 3.42, 95%CI 1.66 to 7.03). In stratified
analysis, increased mortality risk with frailty was observed among both
HIV– persons (HR 2.91, 95%CI 1.06 to 7.96) and HIV+ persons (HR 4.05,
95%CI 1.39 to 11.8). Controlling for advanced HIV infection (CD4 <350,
HIV RNA+), frailty remained a significant predictor of mortality (HR
3.13, 95%CI 1.25 to 7.82). In comparison to non-frail persons, similar
associations of frailty with mortality were observed.

Conclusions:  Frailty is a significant predictor of mortality among
both HIV+ and at-risk IDU. Frailty provides prognostic information even
when accounting for advanced HIV disease suggesting that standardized
assessment may inform prediction of significant clinical endpoints.
Further exploration of the biological mechanisms and clinical utility
of frailty may aid management of aging HIV+ persons.
------------------------

Mitochondrial Function in vivo in Aging HIV+ Patients

Brendan Payne*1,2, M Trenell2, K Hollingsworth2, J Baxter3, V Lee4, E
Wilkins3, A Price1, and P Chinnery2

1Royal Victoria Infirmary, Newcastle upon Tyne, UK; 2Newcastle Univ,
Newcastle upon Tyne, UK; 3Northern Manchester Gen Hosp, UK; and
4Manchester Royal Infirmary, UK

Background:  We have recently demonstrated that patients with prior
exposure to nucleoside analog ARV, which inhibit DNA polymerase-γ,
accumulate acquired mitochondrial DNA (mtDNA) mutations in skeletal
muscle, in an apparent acceleration of the process seen in normal
aging. Here we explore an in vivo functional correlate in aging HIV+
patients.

Methods:  We recruited older HIV+ patients in clinical care (n = 24;
age 48 to 74 years) and age-matched controls (HIV–). Phosphorus
magnetic resonance spectroscopy (31P-MRS) was performed using a 3-T
scanner. Spectra were obtained from gastrocnemius/soleus at rest and
during recovery from brief exercise. Key measures were:  adenosine
triphosphate (ATP) production during recovery (as Qmax (ADP), maximal
rate of adenosine diphosphate (ADP) clearance; τ1/2 (PCr), half-life of
phosphocreatine); and pH handling. In HIV+ subjects, comparison was
made with cellular mitochondrial function by COX (cytochrome c oxidase)
histochemistry of lower-limb muscle biopsy.

Results:  Basal parameters of ATP metabolism differed between subjects
groups:  ADP (mean ±SD) HIV+ 10.2±0.7 mM, HIV– 9.5±0.5 mM (p = 0.001);
PCr HIV+ 41.0±15.2 mM, HIV– 30.7±2.1 mM (p = 0.003). Furthermore, basal
ADP levels in HIV+ subjects correlated with biopsy COX defect (r =
0.45, p = 0.032). In contrast, dynamic measures of ATP production
during exercise recovery were similar in HIV+ and control subjects:
Qmax (ADP) (mean±SD) HIV+ 26.6±18.6 mM/min, HIV– 23.0±10.2 mM/min; τ1/2
(PCr) HIV+ 29.9±13.4 s, HIV– 27.5±8.3 s. There was more variance seen
in the HIV+ than the HIV– group, however no disease or treatment
variable was significantly correlated with ATP production rate, nor was
cellular COX defect. HIV+ subjects showed disordered pH handling
compared with HIV– controls as evidenced by higher basal pH (mean±SD,
7.07±0.03 vs 7.04±0.02, p = 0.001) and post-recovery pH (7.09±0.03 vs
7.06±0.02, p = 0.008) but similar exertional minimum pH (6.98±0.13 vs
7.00±0.03, ns). Resting pH correlated with COX defect (r = 0.42, p =
0.044).

Conclusions:  The altered basal ATP metabolite levels in HIV+ subjects
coupled with preserved dynamic function, despite cellular mitochondrial
defects on biopsy, suggests functional compensation to an acquired
mtDNA defect, once therapy has been switched to a cleaner agent.
Abnormalities of resting muscle pH handling have been associated with
fatigue and may contribute to functional decline in this patient group.
-----------------------

Functional Impairment Is Associated with Low Bone and Muscle Mass in
Middle-aged HIV-1+ Persons

Kristine Erlandson*, A Allshouse, C Jankowski, S MaWhinney, W Kohrt,
and T Campbell
Univ of Colorado Denver, Aurora, US

Background:  Physical function impairment may be accelerated in the
presence of osteoporosis, obesity, or sarcopenia. HIV+ persons have
early physical impairment, but little is known about the contributions
of bone or body composition changes to impairment in persons aging with
HIV-1.

Methods:  We conducted a prospective study of 45- to 65-year-old HIV-1+
subjects who had been on ART >6 months and whose plasma HIV-1 RNA <48
copies/mL. Low functioning (LF) and high functioning (HF) subjects were
identified by deficits on both Fried’s frailty criteria and the Short
Physical Performance Battery and were matched by age, gender, and time
since HIV diagnosis. Bone, fat, and muscle were assessed by
densitometry. Osteoporosis was defined as T-score ≤–2.5, osteopenia as
T-score <–1 but >–2.5, sarcopenia as appendicular skeletal muscle index
(ASMI) <5.45 kg/m2 (female) and <7.26 kg/m2 (male). Insulin-like growth
factor (IGF)-1 and IGF-binding protein (BP)-3 were measured. Stratified
logistic regression for categorical variables and linear mixed effects
regression for continuous variables were estimated to account for
correlation within matched pairs. Body mass index (BMI), tobacco, and
nadir CD4+ T cells were adjusted in models of bone loss.

Results:  We identified 30 LF and matched them to 48 HF subjects; mean
age 52.7 years, CD4 T cell 598, 96% HIV-1 viral load <48 copies/mL, 18%
female, 77% white, 17% Hispanic. LF and HF were similar in age,
duration of ART, tenofovir use, and CD4 T- cells (all p >0.2). LF
subjects had significantly lower BMD and T scores at the hip and spine;
differences remained significant in multivariate analyses. Although all
persons with BMI <18.5 kg/m2 were LF, LF trended toward higher relative
body fat content. LF subjects had a greater prevalence of sarcopenia
(50% vs 25%, p = 0.04), lower lean mass, and lower IGF-1/IGFBP3.

Conclusions:  Impaired functional capacity is strongly associated with
lower bone density and lower muscle mass in middle-aged HIV-1+ persons. 
Whether bone or muscle loss is the result of disuse due to impairment,
or if low muscle or bone mass, mediated through effects of IGF-1, leads
to impairment by progressive weakness or inflammatory pathways remains
to be established. Further studies should investigate the role of
increased muscle/bone mass and increased IGF-1 on preserving functional
independence as persons with HIV age.
--------------------------

Co-morbidity Is Predictive of Muscle Strength in HIV+ Veterans: Results
from the VACS Index

Krisann Oursler*1, J Tate2, T Gill2, K Crothers3, T Brown4, S Crystal5,
J Womack2, D Leaf6, J Sorkin1, A Justice2, and Veterans Aging Cohort
Study Project Team

1Univ of Maryland Sch of Med and Publ Hlth and VA Maryland Hlthcare
System, Baltimore, US; 2Yale Univ Sch of Med and Publ Hlth and VA
Connecticut Hlthcare System, New Haven, US; 3Univ of Washington,
Seattle, US; 4Johns Hopkins Univ, Baltimore, MD, US; 5Rutgers Univ, New
Brunswick, NJ, US; and 6Univ of California, Los Angeles Sch of Med and
Greater Los Angeles VA Hlthcare System, US

Background:  Despite improved survival, HIV+ adults have increased risk
for physical disability due to muscle weakness, poor ambulatory
function, and low cardiorespiratory fitness. The objective of this
study was to determine whether the VACS Index, a comprehensive index of
generalized organ injury based on routine clinical laboratory data, is
associated with hand-grip and leg-strength, 6-minute walk distance, and
cardiorespiratory fitness (peak oxygen consumption, VO2 peak).

Methods:  HIV+ patients enrolled in the Veterans Aging Cohort Study
(VACS) participated in this cross-sectional study at the Baltimore VA
Medical Center from 2004 to 2007. The VACS Index was calculated
incorporating hemoglobin, FIB-4, eGFR, hepatitis C infection, CD4
count, HIV-1 viral load, and age; higher score reflected greater
co-morbidity. Analyses included nonparametric correlation (Spearman’s
rank) and linear regression models.

Results:  We included 2 women and 53 men:  91% African American race,
mean age of 52 (SD 7) years. The VACS Index was inversely correlated
with hand-grip strength (r = –0.36, p = 0.01) and lower extremity
strength (quadriceps, r = –0.45, p <0.01), but was not significantly
associated with 6-minute walk distance (r = –0.26, p = 0.07) or VO2
peak (r = –0.13, p = 0.3). A 20-point higher VACS Index score was
associated with a 10% lower leg strength (mean 76 newtons; 95%CI –124
to –29; p <0.001; see the figure), which remained significant after
adjustment for muscle cross-sectional area (p = 0.04). The VACS Index
explained 34% of the variance in specific leg strength. In contrast, an
index restricted to CD4 count, viral load, and age did not correlate
with any of these measures (p >0.08).

Conclusions:  In this sample of predominantly African American men
ranging in age from 31 to 72 years, the VACS Index was significantly
associated with upper and lower extremity strength. The VACS Index may
be valuable for identification of patients at high risk for disability
due to muscle weakness. Association of Leg Strength with the VACS Index.

Report from the Aging and HIV Workshop- Frailty

Today was the start of the first international workshop on Aging and HIV in Baltimore.

The program was started by Dr L. Ferrucci who gave the first presentation on frailty. He works in geriatrics and presented general data from previous studies in the general aging HIV negative population. He presented compelling data that showed that people lose lean body mass (via a syndrome. called age related sarcopenia) and strength in people as they age, and those decreases are correlated to higher mortality. Also, inflammation markers like interleukin 6 increase with age, and levels of over 2.5 pg/ml in the blood have been linked to disability due to loss of muscle strength and mass. He also added that aging related inflammation can decrease brain volume and may be implicated in depression and other health issues.

Dr Joseph Margolick from the MACS Cohort presented previously published frailty data from this cohort that followed 4959 men who have sex with men since 1984 until 2006. Some of these men got infected with HIV and have been followed up before and after infection. A total of 1045 patients with HIV were followed. 75% of them had undetectable HIV viral load.

The frailty related phenotype (FRP) (i.e., the physical characteristics of frailty) was identified using 1 item selected from the questionnaires for each of the following 4 components: weight loss (answer yes to since your last visit, have you had unintentional weight loss of at least 10 pounds), exhaustion [answer yes to during the past 4 weeks, as a result of your physical health, have you had difficulty performing your work or other activities (for example, it took extra effort)?], slowness (answer yes, limited a lot to does your health now limit you in walking several blocks?), and low physical activity level (answer yes, limited a lot to does your health now limit you in vigorous activities, such as running, lifting heavy objects, participating in strenuous sports?). The assessment of weakness (ie, grip strength) was not incorporated into the MACS protocol until October 2005 and therefore could not be used in defining the FRP. A participant was considered as having the FRP at the visit if at least 3 of the 4 components were present. The FRP thus defined had a prevalence of 4.4% among MACS HIV-uninfected men aged 65 years and older, which was similar to the prevalence of frailty observed in the Cardiovascular Health Study for men of similar ages.

Frailty improved with the introduction of HAART. However, after adjusting for most important factors, frailty was still higher in HIV+ men compared to HIV- men. In fact, frailty of a 55 year old HIV+ man may be similar to that of a 65 year old HIV negative man.

Basal metabolic rate has also been found to be higher in HIV+ men compared to HIV- ones.

No therapeutic intervention data was presented to review the effect of exercise, testosterone replacement, and other factors on frailty in HIV+ men.

Strive To Thrive While Growing Older With HIV

By Dennis McMillan Published: February 11, 2010

Nelson Vergel. Photo by Rink. Positive Force will present “Survivor Health Wisdom: Strive to Thrive While Growing Older with HIV” on Wednesday, Feb. 17, 6:30-9:30 p.m. at the San Francisco LGBT Community Center, 1800 Market and Octavia Streets. Join Nelson Vergel, author of Built to Survive, for the latest information on lipoatrophy, combating premature aging, and much more. A light dinner will be provided. To take advantage of the fact that Vergel will be in the Bay Area for a conference, Positive Force scheduled this event on the third Wednesday of the month. Twice annually, Positive Force produces a community health forum on a hot button issue. “Survivor Health Wisdom...” is a Positive Force community health forum.In this instance, they decided to do a forum on HIV and aging. The face of HIV changes with each passing day. For example, thanks to treatment advances, many people living with HIV today are living longer lives. Along with longer lives come the usual health concerns: increased risks for heart disease, non-HIV related cancers, bone loss, decreased mental function, etc. However, a plethora of recent research has clearly demonstrated that people living with HIV are suffering from accelerated aging; sometimes their minds and bodies manifest problems decades earlier than their HIV-negative counterparts. Consequentially, researchers, medical providers, treatment advocates, and HIV-positive people alike are trying to figure out how to conquer this new phase of living with HIV. Many community forums on HIV and aging involve doctors and other socio-medical professionals speaking clinically, and providing the same information, from the same point of view, time and time again. Positive Force decided to move in a different direction. They invited Vergel, a man who has lived with HIV for more than two decades and who is an internationally renowned treatment advocate, to discuss HIV and aging concerns from a peer perspective. Vergel has traveled the world talking about living and thriving with HIV; has written books on the topic; and has been featured in numerous publications for his expertise and perspective. Participants who attend the forum will benefit from Vergel’s unique perspective, presentation style, and lots of information. He will present the latest treatment information, both clinical and practical, for a range of subjects, including but not limited to lipodystrophy/ lipoatrophy, accelerated aging of both mind and body, and sexual health. Forum attendees will walk away with a better handle on how to deal with problems they may already be facing and how to prevent new problems associated with HIV and aging. Vergel is a 27-year HIV survivor, Venezuelan, retired chemical engineer, lecturer and author of Built to Survive, founder of the Body Positive Wellness Clinic in Houston, and treatment activist involved in research advocacy. Bay Times interviewed him recently. “I am the founder of pozhealth at yahoogroups.com, the largest online health discussion group, and serve as an expert at thebody.com, the HIV web site with the largest reach in HIV related health issues,” he said. “I have provided over 600 lectures since 1994 in English and Spanish. I am a member of the DHHS HIV Treatment Guidelines Panel. I have presented in many conferences about issues related to living with HIV.” What is different about what he does is his being able to lecture in layman terms by blending the latest research data with a patient perspective. He spoke of the hot topics in HIV in the next five years. “The search for a cure using stem cell and immune based therapy research will become more important as well as how to deal with long term effects of HIV medications on aging, frailty, cognitive function, bone density, frailty, body changes, and others,” said Vergel. “Combating stigma and dealing with challenges in funding will be essential to controlling the spread of this epidemic.” Vergel provides a unique angle to patients. He speaks in their language about the latest research findings on facial lipoatrophy options, cardiovascular health, sexual dysfunction, hormonal balance, exercise and nutrition, latest HIV medications for those with limited treatment options, side effect management, and many other issues that are important to patients.

An Anti-frailty Pill For Seniors? New Drug Increases Muscle Mass In Arms And Legs Of Older Adults

I bet this could compete with Theratecnologies/Serono's Tesamorelin eventually. But Merck is smart going after baby aging boomers

An Anti-frailty Pill For Seniors? New Drug Increases Muscle Mass In Arms And Legs Of Older Adults
ScienceDaily (Nov. 5, 2008) — Researchers at the University of Virginia Health System report that a daily single oral dose of an investigational drug, MK-677, increased muscle mass in the arms and legs of healthy older adults without serious side effects, suggesting that it may prove safe and effective in reducing age-related frailty.

Published in the November 4, 2008 issue of Annals of Internal Medicine, the study showed that levels of growth hormone (GH) and of insulin-like growth factor I (IGF- I) in seniors who took MK-677 increased to those found in healthy young adults. The drug restored 20 percent of muscle mass loss associated with normal aging.

"Our study opens the door to the possibility of developing treatments that avert the frailty of aging," explains Dr. Michael O. Thorner, a nationally recognized researcher of growth hormone regulation and a professor of internal medicine and neurosurgery at UVA. "The search for anti-frailty medications has become increasingly important because the average American is expected to live into his or her 80s, and most seniors want to stay strong enough to remain independent as they age."

Funded by the National Institutes of Health, the two-year, double-blind, placebo-controlled, modified-crossover study involved 65 men and women ranging in age from 60 to 81.

The study drug, MK-677, mimics the action of ghrelin, a peptide that stimulates the growth hormone secretagogue receptor (GHSR). Drug developers are focusing on GHSR because it plays an important role in the regulation of growth hormone and appetite. They think it may prove to be an excellent treatment target for metabolic disorders such as those related to body weight and body composition.

According to Dr. Thorner, the UVA research was a "proof-of-concept" study that sets the stage for a larger and longer clinical trial to determine whether MK-677 is effective in people who are frail and to assess its long term safety.


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University of Virginia Health System (2008, November 5). An Anti-frailty Pill For Seniors? New Drug Increases Muscle Mass In Arms And Legs Of Older Adults. ScienceDaily. Retrieved November 10, 2008, from http://www.sciencedaily.com /releases/2008/11/081104132902.htm